Neurodevelopmental disorders according to the dsm 5 tr
Biochemistry-Unit 5.pptx
1. BIOCHEMISTRY
• Carbohydrate is a group of organic compounds occurring in living tissues and foods in the form of starch, cellulose, and sugars
• The ratio of oxygen and hydrogen in carbohydrates is the same as in water i.e. 2:1. It typically breaks down in the animal body to release
energy.
What are Carbohydrates?
• Cn(H2O)n is the generic formula for all carbohydrates
• This formula is only valid for simple sugars, which are made up of the same amount of carbon and water.
• Originally the term carbohydrate was used to describe compounds that were literally “carbohydrates,” because they had the empirical formula
CH2O
• Carbohydrates have been classified in recent years on the basis of carbohydrate structures, not their formulae
• Such aldehydes and ketones are now known as polyhydroxy
• Cellulose, starch, and glycogen are among the compounds that belong to this family.
What is the General Formula of Carbohydrates?
• The general formula for carbohydrates is Cx(H2O)y
• Carbohydrates (or sugars) were originally believed to be “hydrates of carbon,” because they have the general
formula C (H O)y.
Unit - V Carbohydrates
2. Definition of Carbohydrates
• Chemically, carbohydrates are defined as “optically active polyhydroxy aldehydes or ketones or the compounds which produce units
of such type on hydrolysis”
• The substance most people refer to as “sugar” is the sucrose disaccharide, which is extracted either from sugar cane or beets
• Sucrose is the disaccharide most sweet
• It’s approximately three times sweet as maltose, and six times sweet as lactose
• In recent years, in many consumer products, sucrose has been replaced with corn syrup, which is obtained when the polysaccharides in
cornstarch are broken down
• Corn syrup is primarily glucose, which is as sweet as sucrose only about 70 per cent
Carbohydrates are also called saccharides which is a Greek word it means sugar because almost all carbohydrates have a sweet taste.
Carbohydrates Definition in Science
• The term carbohydrate or hydrates of carbon is derived from its basic elemental formula in which carbon is joined to hydrogen and oxygen
present in the same ratio as in water
• Chemically carbohydrates are polyhydroxy aldehydes or ketones, their simple derivatives or their polymers
• Carbohydrates in grains are classified based on their chemical structures or their digestibility when consumed by humans as food or by
livestock as feed
• Simple carbohydrates which are sweet and soluble in water are also known as sugars or disaccharides and the ending of the names of most
sugars is –ose
• Thus, we have such names as sucrose for ordinary table sugar, glucose for principal sugar in blood and maltose for malt sugar
3. Carbohydrates Structure
• Historically carbohydrates were defined as substances with the empirical formula Cn(H2O)m
• The common sugars such as glucose and fructose or sucrose fit this formula, but nowadays the convention is to regard as a
carbohydrate a polyhydroxy aldehydes or polyhydroxy ketone with the classical formula, a molecule closely related to it, or
oligomers or polymers of such molecules
• Their study evolved as a separate sub-discipline within organic chemistry for practical reasons – they are water-soluble and
difficult to crystallise so their manipulation demanded different sets of skills from classical “natural products” such as terpenes,
steroids, alkaloids, etc
• The term “monosaccharide” refers to a carbohydrate derivative possessing a single carbon chain; “disaccharide” and
“trisaccharide” refer to molecules containing two or three such monosaccharide units joined together by acetal or ketal linkages
• “Oligosaccharide” and “polysaccharide” refer to larger such aggregates, with “a few” and many monosaccharide units,
respectively
• Current usage seems to draw the distinction between “few” and many at around 10 units.
4. • By the middle of the nineteenth century, a number of relatively pure carbohydrates such as sucrose, cellulose from cotton, starch, glucose,
fructose, mannose and lactose were known to the chemists of Europe, especially in Germany
• In 1878, Emil Fischer synthesized phenyl hydrazine for his thesis at the University of Munich
• In 1884 he further discovered that carbohydrates gave crystalline phenylosazone in which two phenyl hydrazines reacted with the aldehyde
group and the carbon adjacent to the aldehyde group
Carbohydrates Formula
• Carbohydrates are large macromolecules consisting of carbon (C), hydrogen (H) and oxygen (O) and have the general Cx(H2O)y formula
• The hydrate of carbon is known as carbohydrates
• They contain hydrogen and oxygen in the same proportion as in water
• It may be noted that there are some carbohydrates which do not conform to the formula Cx(H2O)y, for example, 2-deoxyribose C5H10O4
• However, most of them conform to the formula Cx(H2O)y
5. • Carbohydrates are also called sugars in general some partially methylated sugars and amino sugars and amino sugars naturally and one
natural nitro sugar is known
• All carbohydrates are polyhydroxy aldehydes or ketones or substances that yield these on hydrolysis
• Haworth projections represent the cyclic structures of monosaccharides
• Monosaccharides contain either an aldehyde group (aldose) or a ketone group (ketose) and several -OH groups
• Straight chain forms of sugars cyclize in solution to form ring structures containing an ether linkage
• Glycosidic bonds form between monosaccharides forming disaccharides and polysaccharides
• Carbohydrates are used as energy sources and energy reserves.
Sources of Carbohydrates
We know carbohydrates are an important part of any human’s diet. Some common sources of carbohydrates are:
1.Potatoes
2.Maze
3.Milk
4.Popcorn
5.Bread
7. Types of Carbohydrates – Simple Carbohydrates
• Simple carbohydrates are the basic type of carbs
• Soft drinks, candy, cookies and other sweet snacks contain simple carbohydrates
• These foods are often made with white sugar, a form of processed sugar
• Simple carbohydrates also are found in natural sugars
• Fruit, milk and vegetables contain natural sugars
• Honey is a natural sugar as well
• People eat natural sugar in its original form
• Simple carbohydrates are easier to handle because they are less (or simpler) complex
• They come from fruit and sugar stuff, as well as pretty much anything else that’s sweet
• The human body can rapidly break down these things, and that is where some of the problems lie
• There is only one sugar unit in the monosaccharides, so they are the smallest of the carbohydrates
• “The small size of monosaccharides gives them a special role in digestion and metabolism
• (The prefix” mono- “means” one.) Before they can be ingested into the gastrointestinal tract, food carbohydrates have to be broken down into
monosaccharides and they also flow in monosaccharide form in the blood.
8. Types of Carbohydrates – Complex Carbohydrates
• Complex carbohydrates represent an important energy source for your body
• They provide the sustained fuel your body needs for exercise, daily living activities and even rest
• Complex carbohydrates are often single units (monosaccharides), which are bound together
• The oligosaccharides contain two to ten simple units of sugar
• Polysaccharides contain hundreds and thousands of monosaccharides which are related.
• Complex carbohydrates have fairly long-lasting energy
The different types of carbohydrates can be classified on the basis of their behavior in hydrolysis
• They are mainly classified into three groups:
1.Monosaccharides
2.Disaccharides
3.Polysaccharides
9. Monosaccharides
• Monosaccharide carbohydrates are those carbohydrates that cannot be hydrolyzed further to give simpler units of polyhydroxy aldehyde or
ketone.
• If a monosaccharide contains an aldehyde group then it is called aldose and on the other hand, if it contains a keto group then it is called a
ketose
Structure of Carbohydrates – Glucose
• One of the most important monosaccharides is glucose.
• The two commonly used methods for the preparation of glucose are
From Sucrose: If sucrose is boiled with dilute acid in an alcoholic solution then we obtain glucose and fructose.
From Starch: We can obtain glucose by hydrolysis of starch and by boiling it with dilute H2SO4 at 393K under elevated pressure.
•Glucose is also called aldohexose and dextrose and is abundant on earth
•Glucose is named as D (+)-glucose, D represents the configuration whereas (+) represents the dextrorotatory nature of the molecule.
•The ring structure of glucose can explain many properties of glucose which cannot be figured by open-chain structure.
10. •The two cyclic structures differ in the configuration of the hydroxyl group at C1 called anomeric carbon.
•Such isomers i.e. α and β form are known as anomers.
•The cyclic structure is also called pyranose structure due to its analogy with pyran
•The cyclic structure of glucose is given below:
11. Structure of Carbohydrates – Fructose
• It is an important ketohexose.
• The molecular formula of fructose is C6H12O6 and contains a ketonic functional group at carbon number 2 and has six carbon atoms in a straight
chain
• The ring member of fructose is in analogy to the compound Furan and is named furanose
• The cyclic structure of fructose is shown below:
Examples of Carbohydrates
Here are a few examples of where you’ll find the most carbs:
•Dairy Products – Yogurt, Milk, Ice cream
•Fruits – Fruit juice or Whole fruit
•Grains – Cereal, Bread, Wheat, Rice
•Legumes – Plant-based proteins, Beans
•Starchy Vegetables – Corn, Potatoes
12. 2. Disaccharides
•On hydrolysis, disaccharides yield two molecules of either the same or different monosaccharides.
•The two monosaccharide units are joined by oxide linkage which is formed by the loss of water molecule and this linkage is called glycosidic
linkage.
•Sucrose is one of the most common disaccharides which on hydrolysis gives glucose and fructose.
•Maltose and Lactose (also known as milk sugar) are the other two important disaccharides.
•In maltose, there are two α-D-glucose and in lactose, there are two β-D-glucose which are connected by an oxide bond.
3. Polysaccharides
•Polysaccharides contain long monosaccharide units joined together by glycosidic linkage.
•Most of them act as food storage for e.g. Starch. Starch is the main storage polysaccharide for plants.
•It is a polymer of α glucose and consists of two components-Amylose and Amylopectin.
•Cellulose is also one of the polysaccharides that are mostly found in plants.
•It is composed of β-D- glucose units joined by a glycosidic linkage between C1 of one glucose unit and C4 of the next glucose unit.
13. Frequently Asked Questions – FAQs
What are carbohydrates?
Carbohydrates are the sugars, starches and fibres present in the products of fruits, grains, vegetables and milk. The American Diabetes
Association states that carbohydrates are the primary source of energy for the body. They are called carbohydrates, as they contain carbon,
hydrogen and oxygen at the chemical level.
What types of foods are carbohydrates?
Carbohydrates are present in a wide range of safe as well as unhealthy foods — bread, beans, milk, popcorn, potatoes, cookies, pasta, soft
drinks, corn, and cherry pie. They come in a range of shapes too. The most natural and abundant types are sugars, starches and fibres.
What are the major functions of carbohydrates?
The four primary carbohydrate functions in the body are to provide energy, store energy, create macromolecules and spare protein and fat for
other uses. Glucose energy is processed in the form of glycogen, with most in the muscle and liver.
What are the main carbohydrates?
Foods rich in carbohydrates include bread, vegetables and fruits, as well as dairy. Carbohydrates are the sugars, starches and fibres present
in the products of fruits, grains, vegetables and milk. Even though often maligned in trendy diets, carbohydrates are essential to a healthy diet
as one of the basic food groups.
What are the two sources of carbohydrates?
Healthy carbohydrate sources include both animal and plant food sources, such as fresh fruits, tomatoes, corn, potatoes, meat, and milk
products. Examples that are not safe include soda, white bread, added sugar, pastries and other highly processed food.
14. What is a simple carbohydrate?
The body rapidly breaks down simple carbohydrates to be used as energy. Simple carbohydrates are naturally found in foods such
as fruit, milk, and dairy products. In processed and refined sugars such as candy, table sugar, syrups and soft drinks, are also
found.
What is a complex carbohydrate?
Simple carbohydrates consist of sugar molecules, which are bound together in long, complex chains. Foods such as peas, beans,
whole grains, and vegetables contain complex carbohydrates. Within the body, both simple and complex carbohydrates are
converted into glucose ( blood sugar) and used as energy.
What is the difference between complex and simple carbohydrates?
Simple carbohydrates are present in such foods as table sugar and syrups. Complex carbohydrates contain longer sugar molecular
chains than mere carbohydrates. Since complex carbohydrates have longer chains, they take longer than simple carbohydrates to
break down and provide more lasting energy in the body.
15. Synthesis and breakdown of starch and cellulose
Breakdown of Starch:
Breakdown or the hydrolysis of starch to yield its constituent a-D-Glucose units may take place in two ways:
(1) By the enzyme diastase:
In fact diastase is not a single enzyme but a complex of many enzymes which are as follows:
(i) α-amylase,
(ii) β-amylase,
(iii) R-Enzyme,
(iv) Maltase
α-amylase and β-amylase attack 1 : 4 linkages of amylose and amylopectin (which constitute the starch) while R-Enzyme attacks 1 : 6 linkages
of amylopectin, so that starch is hydrolysed to yield disaccharide units i.e., maltose. Finally, the enzyme maltase converts maltose into glucose
molecules.
(2) By the enzyme starch phosphorylase.
Glucose-1-Phosphate may be converted into glucose by the enzyme phosphatase.
16. Synthesis of Starch:
Synthesis of starch involves the simultaneous synthesis of amylose (with α-(1: 4) glycosidic linkages) and amylopectin (with α-(1: 6) glycosidic
linkages), the two important constituents of starch. These are storage molecules to store sugar. They are polysaccharides.
(A) Synthesis of Amylose (Or α-(1: 4) Glycosidic Linkages):
Synthesis of amylose may take place by any of the following ways:-
(1) According to Hanes (1940) amylose can be synthesised in the presence of the enzyme starch phosphorylase from glucose-1-phosphate and
an acceptor molecule consisting of about 3 to 20 glucose units joined together by α-(1: 4) glycosidic linkages.
(2) Formation of α-(1 : 4) glycosidic linkages may also take place in the presence of the enzyme UDPG-transglycosylase (amylose synthetase)
by the transfer of glucose from UDPG (Uridine Di Phosphate Glucose) to an acceptor molecule consisting of 2 to 4 or more glucose units joined
together by α-(1 : 4) glycosidic linkages or even a starch molecule.
17. (3) According to Akazawa et al (1964) glucose molecule obtained as a result of the hydrolysis of sucrose in the presence
of enzyme sucrase is transferred to UDP (Uridine Di Phosphate) molecule to form UDPG. Form UDPG the glucose
molecule is transferred to starch
(4) Formation of α-(1: 4) glycosidic linkages leading to the synthesis of; amylose may also take place in the presence of
D-Enzyme by the transfer of two or more glucose units from maltodextrins (consisting of more than two glucose units)
to a variety of acceptors such as malto troise, malto tetrose molecules.
18. Breakdown of Cellulose:
• Cellulose is a straight chain polymeric carbohydrate molecule (a glucan), composed of a large number of D-
glucopyranose units joined together by β(1 → 4) glycosidic linkages
• In nature, cellulose is broken down by enzymatic hydrolysis through the enzymes called celluloses
• These enzymes which are often grouped under generic name cellulase, randomly attack β(1 → 4) glycosidic
linkages of the cellulose chain first forming cellodextrins and then disaccharides called as cellobiose
• Cellobiose is then hydrolyzed to glucose by the enzyme cellobiose
• Cellulose degrading enzymes are not found in plants or humans
• These are found only in certain organisms such as ruminants, termites, some bacteria and certain protozoa
• (Division Ruminantia of even-toed ungulates such as a deer, antelope, sheep, goat or cow).
19. Synthesis of Cellulose:
• Long un-branched chains of cellulose (consisting of β(1→4) linked glucose residues) are synthesized in plants by the
enzymes called cellulose synthases
• The enzyme cellulose synthase is a multi-submit complex that is situated on plasma membrane and transfers a
glucose residue from a sugar nucleotide donor called uridine diphosphate glucose (UDPG) to an acceptor molecule
forming β (1 → 4) glucosyl acceptor
UDPG + Acceptor → UDP + β (1→4) glucosyl-acceptor
• It is believed that sterol-glycosides (i.e., sterols joined to a chain of one or more glucose units) such as β-sitosterol
glucoside probably act as initial acceptors that start the elongation of cellulose chain
• The process continues, and after the cellulose chain has attained desired length, the sterol is cut off from the glucan
(Cellulose Chain) by the enzyme endoglucanase present in the plasma membrane
• The separated cellulose chains are then extruded on the
outer side of the plasma membrane
20. • There are evidences to suggest that glucose in UDPG comes from sucrose, by the action of the reversible enzyme
sucrose synthetase
• Alternatively, UDP-glucose may be directly obtained from cytoplasm.
21. Unit - VI Lipids
General classification of lipids
What are Lipids?
• These organic compounds are nonpolar molecules, which are soluble only in nonpolar solvents and insoluble in water because water is a
polar molecule
• In the human body, these molecules can be synthesized in the liver and are found in oil, butter, whole milk, cheese, fried foods and also in
some red meats
22. Properties of Lipids
Lipids are a family of organic compounds, composed of fats and oils. These molecules yield high energy and are responsible for
different functions within the human body. Listed below are some important characteristics of Lipids.
1.Lipids are oily or greasy nonpolar molecules, stored in the adipose tissue of the body.
2.Lipids are a heterogeneous group of compounds, mainly composed of hydrocarbon chains.
3.Lipids are energy-rich organic molecules, which provide energy for different life processes.
4.Lipids are a class of compounds characterised by their solubility in nonpolar solvents and insolubility in water.
5.Lipids are significant in biological systems as they form a mechanical barrier dividing a cell from the external environment known as the
cell membrane.
Lipid Structure
Lipids are the polymers of fatty acids that contain a long, non-polar hydrocarbon
chain with a small polar region containing oxygen. The lipid structure is explained in
the diagram below:
Lipid Structure – Saturated and Unsaturated
Fatty Acids
23. Classification of Lipids
Lipids can be classified into two main classes:
•Nonsaponifiable lipids
•Saponifiable lipids
Nonsaponifiable Lipids
• A nonsaponifiable lipid cannot be disintegrated into smaller molecules through hydrolysis
• Nonsaponifiable lipids include cholesterol, prostaglandins, etc
Saponifiable Lipids
• A saponifiable lipid comprises one or more ester groups, enabling it to undergo hydrolysis in the presence of a base, acid,
or enzymes, including waxes, triglycerides, sphingolipids and phospholipids
• Further, these categories can be divided into non-polar and polar lipids
• Nonpolar lipids, namely triglycerides, are utilized as fuel and to store energy
• Polar lipids, that could form a barrier with an external water environment, are utilized in membranes
• Polar lipids comprise sphingolipids and glycerophospholipids
• Fatty acids are pivotal components of all these lipids.
24. Types of Lipids
• Within these two major classes of lipids, there are numerous specific types of lipids, which are important to life, including fatty acids,
triglycerides, glycerophospholipids, sphingolipids and steroids
• These are broadly classified as simple lipids and complex lipids.
Simple Lipids
Esters of fatty acids with various alcohols.
1.Fats: Esters of fatty acids with glycerol. Oils are fats in the liquid state
2.Waxes: Esters of fatty acids with higher molecular weight monohydric alcohols
Complex Lipids
Esters of fatty acids containing groups in addition to alcohol and fatty acid.
1.Phospholipids: These are lipids containing, in addition to fatty acids and alcohol, phosphate group
• They frequently have nitrogen-containing bases and other substituents, eg, in glycerophospholipids the alcohol is glycerol and in
sphingophospholipids the alcohol is sphingosine.
2.Glycolipids (glycosphingolipids): Lipids containing a fatty acid, sphingosine and carbohydrate.
3.Other complex lipids: Lipids such as sulfolipids and amino lipids. Lipoproteins may also be placed in this category.
Precursor and Derived Lipids
• These include fatty acids, glycerol, steroids, other alcohols, fatty aldehydes, and ketone bodies, hydrocarbons, lipid-soluble vitamins, and
hormones
• Because they are uncharged, acylglycerols (glycerides), cholesterol, and cholesteryl esters are termed neutral lipids
• These compounds are produced by the hydrolysis of simple and complex lipids
25. Fatty Acids
Fatty acids are carboxylic acids (or organic acid), usually with long aliphatic tails (long chains), either unsaturated or saturated.
Saturated fatty acids
• Lack of carbon-carbon double bonds indicate that the fatty acid is saturated
• The saturated fatty acids have higher melting points compared to unsaturated acids of the corresponding size due to their
ability to pack their molecules together thus leading to a straight rod-like shape.
Unsaturated fatty acids
• Unsaturated fatty acid is indicated when a fatty acid has more than one double bond
• “Often, naturally occurring fatty acids possesses an even number of carbon atoms and are unbranched.”
• On the other hand, unsaturated fatty acids contain a cis-double bond(s) which create a structural kink that disables them to
group their molecules in straight rod-like shape.
Role of Fats
Fats play several major roles in our body. Some of the important roles of fats are mentioned below:
•Fats in the correct amounts are necessary for the proper functioning of our body.
•Many fat-soluble vitamins need to be associated with fats in order to be effectively absorbed by the body.
•They also provide insulation to the body.
•They are an efficient way to store energy for longer periods
26. Examples of Lipids
There are different types of lipids. Some examples of lipids include butter, ghee, vegetable oil, cheese, cholesterol and other steroids, waxes,
phospholipids, and fat-soluble vitamins. All these compounds have similar features, i.e. insoluble in water and soluble in organic solvents, etc.
Waxes
• Waxes are “esters” (an organic compound made by replacing the hydrogen with acid by an alkyl or another organic group) formed from long-
alcohols and long-chain carboxylic acids
• Waxes are found almost everywhere. The fruits and leaves of many plants possess waxy coatings, that can safeguard them from small
predators and dehydration
• Fur of a few animals and the feathers of birds possess the same coatings serving as water repellants
• Carnauba wax is known for its water resistance and toughness (significant for car wax).
Phospholipids
• Membranes are primarily composed of phospholipids that are Phosphoacylglycerols
• Triacylglycerols and phosphoacylglycerols are the same, but, the terminal OH group of the phosphoacylglycerol is
esterified(combined with alcohol or acid) with phosphoric acid in place of fatty acid which results in the formation of
27. Steroids
• Our bodies possess chemical messengers known as hormones, which are basically organic compounds synthesized in glands and transported by the
bloodstream to various tissues in order to trigger or hinder the desired process
• Steroids are a kind of hormone that is typically recognized by their tetracyclic skeleton, composed of three fused six-membered and one five-membered ring
Cholesterol
•Cholesterol is a wax-like substance, found only in animal source foods
•Triglycerides, LDL( low density lipoprotein), HDL, VLDL are different types of cholesterol found in the blood cells.
•Cholesterol is an important lipid found in the cell membrane
•It is a sterol, which means that cholesterol is a combination of steroid and alcohol
•In the human body, cholesterol is synthesized in the liver.
•These compounds are biosynthesized by all living cells and are essential for the structural component of the cell membrane.
•In the cell membrane, the steroid ring structure of cholesterol provides a rigid hydrophobic structure that helps boost the rigidity of the cell membrane
•Without cholesterol, the cell membrane would be too fluid.
•It is an important component of cell membranes and is also the basis for the synthesis of other steroids, including the sex hormones estradiol and testosterone,
as well as other steroids such as cortisone and vitamin D.
28. Frequently Asked Questions
What are lipids?
Lipids are organic compounds that are fatty acids or derivatives of fatty acids, which are insoluble in water but soluble in organic solvents. For eg., natural oil,
steroid, waxes.
How are lipids important to our body?
Lipids play a very important role in our body. They are the structural component of the cell membrane. They help in providing energy and produce hormones in our
body. They help in the proper digestion and absorption of food. They are a healthy part of our diet if taken in proper amounts. They also play an important role in
signalling.
How are lipids digested?
The enzyme lipase breaks down fats into fatty acids and glycerol, which is facilitated by bile in the liver.
What is lipid emulsion?
It refers to an emulsion of lipid for human intravenous use. These are also referred to as intralipids which is the emulsion of soybean oil, glycerin and egg
phospholipids. It is available in 10%, 20% and 30% concentrations.
How are lipids metabolized?
Lipid metabolism involves the oxidation of fatty acids to generate energy to synthesize new lipids from smaller molecules. The metabolism of lipids is associated
with carbohydrate metabolism as the products of glucose are converted into lipids.
How are lipids released in the blood?
The medium-chain triglycerides with 8-12 carbons are digested and absorbed in the small intestine. Since lipids are insoluble in water, they are
carried to the bloodstream by lipoproteins which are water-soluble and can carry the lipids internally.
What are the main types of lipids?
There are two major types of lipids- simple lipids and complex lipids. Simple lipids are esters of fatty acids with various alcohols. For eg., fats and
waxes. On the contrary, complex lipids are esters of fatty acids with groups other than alcohol and fatty acids. For eg., phospholipids and
sphingolipids.
What are lipids made up of?
Lipids are made up of a glycerol molecule attached to three fatty acid molecules. Such a lipid is called triglyceride.
29. β-oxidation mechanism
Beta Oxidation Definition
• Beta oxidation is a metabolic process involving multiple steps by which fatty acid molecules are broken down to
produce energy
• More specifically, beta oxidation consists in breaking down long fatty acids that have been converted to acyl-CoA
chains into progressively smaller fatty acyl-CoA chains
• This reaction releases acetyl-CoA, FADH2 and NADH, the three of which then enter another metabolic process
called citric acid cycle or Krebs cycle, in which ATP is produced to be used as energy
• Beta oxidation goes on until two acetyl-CoA molecules are produced and the acyl-CoA chain has been completely
broken down
• In eukaryotic cells, beta oxidation takes place in the mitochondria, whereas in prokaryotic cells, it happens in the
cytosol
• For beta oxidation to take place, fatty acids must first enter the cell through the cell membrane, then bind to
coenzyme A (CoA), forming fatty acyl CoA and, in the case of eukaryotic cells, enter the mitochondria, where beta
oxidation occurs
30. Where Does Beta Oxidation Occur?
• Beta oxidation occurs in the mitochondria of eukaryotic cells and in the cytosol of prokaryotic cells
• However, before this happens, fatty acids must first enter the cell and, in the case of eukaryotic cells, the
mitochondria
• In cases where fatty acid chains are too long to enter the mitochondria, beta oxidation can also take place in
peroxisomes
• First, fatty acid protein transporters allow fatty acids to cross the cell membrane and enter the cytosol, since the
negatively charged fatty acid chains cannot cross it otherwise
• Then, the enzyme fatty acyl-CoA synthase (or FACS) adds a CoA group to the fatty acid chain, converting it to acyl-
CoA
• Depending on the length, the acyl-CoA chain will enter the mitochondria in one of two ways:
1.If the acyl-CoA chain is short, it can freely diffuse through the mitochondrial membrane.
2.If the acyl-CoA chain is long, it needs to be transported across the membrane by the carnitine shuttle
• For this, the enzyme carnitine palmitoyltransferase 1 (CPT1)—bound to the outer mitochondrial membrane—
converts the acyl-CoA chain to an acylcarnitine chain, which can be transported across the mitochondrial membrane
by carnitine translocase (CAT)
31. • Once inside the mitochondria, CPT2—bound to the inner mitochondrial membrane—converts the acylcarnitine back
to acyl-CoA. At this point, acyl-CoA is inside the mitochondria and can now undergo beta oxidation
• As mentioned above, if the acyl-CoA chain is too long to be processed in the mitochondria, it will be broken down
by beta oxidation in the peroxisomes
• Research suggests that very long acyl-CoA chains are broken down until they are 8 carbons long, after which they
are transported and enter the beta oxidation cycle in the mitochondria
• Beta oxidation in the peroxisomes yields H2O2 (hydrogen peroxide) instead of FADH2 and NADH, producing heat as a
result
Beta Oxidation Steps
• Beta oxidation takes place in four steps: dehydrogenation, hydration, oxidation and thyolisis
• Each step is catalyzed by a distinct enzyme
• Briefly, each cycle of this process begins with an acyl-CoA chain and ends with one acetyl-CoA, one FADH2, one
NADH and water, and the acyl-CoA chain becomes two carbons shorter
• The total energy yield per cycle is 17 ATP molecules.
• This cycle is repeated until two acetyl-CoA molecules are formed as opposed to one acyl-CoA and one acetyl-CoA.
• The four steps of beta oxidation are described below and can be seen in the links to the figures at the end of each
32. Dehydrogenation
• In the first step, acyl-CoA is oxidized by the enzyme acyl CoA dehydrogenase
• A double bond is formed between the second and third carbons (C2 and C3) of the acyl-CoA chain entering the beta
oxidation cycle; the end product of this reaction is trans-Δ2-enoyl-CoA (trans-delta 2-enoyl CoA)
• This step uses FAD and produces FADH2, which will enter the citric acid cycle and form ATP to be used as energy
(Notice in the following figure that the carbon count starts on the right side: the rightmost carbon below the oxygen
atom is C1, then C2 on the left forming a double bond with C3, and so on)
Hydration
• In the second step, the double bond between C2 and C3 of trans-Δ2-enoyl-CoA is hydrated, forming the end product L-
β-hydroxy acyl CoA, which has a hydroxyl group (OH) in C2, in place of the double bond
• This reaction is catalyzed by another enzyme: enoyl CoA hydratase. This step requires water
33. Oxidation
In the third step, the hydroxyl group in C2 of L-β-hydroxyacyl CoA is oxidized by NAD+ in a reaction that is catalyzed by
3-hydroxyacyl-CoA dehydrogenase. The end products are β-ketoacyl CoA and NADH + H. NADH will enter the citric acid
cycle and produce ATP that will be used as energy.
Thiolysis
Finally, in the fourth step, β-ketoacyl CoA is cleaved by a thiol group (SH) of another CoA molecule (CoA-SH). The
enzyme that catalyzes this reaction is β-ketothiolase. The cleavage takes place between C2 and C3; therefore, the end
products are an acetyl-CoA molecule with the original two first carbons (C1 and C2), and an acyl-CoA chain two carbons
shorter than the original acyl-CoA chain that entered the beta oxidation cycle.
34. End of Beta Oxidation
• In the case of even-numbered acyl-CoA chains, beta oxidation ends after a four-carbon acyl-CoA chain is broken
down into two acetyl-CoA units, each one containing two carbon atoms
• Acetyl-CoA molecules enter the citric acid cycle to yield ATP.
• In the case of odd-numbered acyl-CoA chains, beta oxidation ensues in the same way except for the last step:
instead of a four-carbon acyl-CoA chain being broken down into two acetyl-CoA units, a five-carbon acyl-CoA chain is
broken down into a three-carbon propionyl-CoA and a two-carbon acetyl-CoA
• Another chemical reaction then converts propionyl-CoA to succinyl-CoA, which enters the citric acid cycle to produce
ATP.
35. Energy Yield and End Products
Each beta oxidation cycle yields 1 FADH2, 1 NADH and 1 acetyl-CoA, which in terms of energy is equivalent to 17 ATP
molecules:
•1 FADH2 (x 2 ATP) = 2 ATP
•1 NADH (x 3 ATP) = 3 ATP
•1 acetyl-CoA (x 12 ATP) = 12 ATP
Total = 2 + 3 + 12 = 17 ATP
• However, the theoretical ATP yield is higher than the real ATP yield. In reality, the equivalent of about 12 to 16 ATPs
is produced in each beta oxidation cycle
• Besides energy yield, the fatty acyl-CoA chain becomes two carbons shorter with each cycle
• In addition, beta oxidation yields great amounts of water; this is beneficial for eukaryotic organisms such as camels
given their limited access to drinkable water.
36. UNIT-VII: Amino Acids and Proteins
Structure of amino acids
What is the General Molecular Structure of an Amino Acid?
• Amino acids are organic compounds that combine to form proteins
• The general formula of an amino acid is R-CH(NH2)-COOH
• Amino acids are known to contain amine and carboxyl functional groups
• They also contain a side chain that is made up of an R-group (where ‘R’ can denote any alkyl or aryl group)
• These R-groups are what differentiate amino acids and are responsible for their unique properties.
Structure of Amino Acid
The general structure of an amino acid is illustrated below.
• From the illustration, it can be noted that the key elements that make up amino acids are hydrogen,
carbon, nitrogen, and oxygen
• However, it is not uncommon for other elements to be found in the side chain of an amino acid
• It can also be noted that there are over 500 naturally occurring amino acids known to us
• Of these, only 20 amino acids are known to appear in genetic code.
• In the human body, these biomolecules are involved in many biological and chemical functions and are
important ingredients for human growth and development
• Amino acids usually have a melting and boiling point that is very high
• They usually exist in the form of white, crystalline, stable compounds
• A few amino acids are known to be sweet, tasteless, and bitter in flavour
• Most amino acids are water soluble
• However, it can also be noted that most amino acids are insoluble in organic solvents.
37. Some Common Amino Acids and Their Structures
The structures of some common amino acids, such as glycine, serine, leucine, cysteine, and valine have been illustrated below.
38. Glycine
• Glycine is an amino acid that contains, in its side chain, only a single hydrogen atom
• It is known to be the simplest amino acid with the chemical formula NH2-CH2-COOH (because carbamic acid is known to be unstable)
• Glycine is known to be a protein-genic amino acid
• Glycine, due to its compact shape, is integral to the formation of alpha-helices in the secondary protein structure
• For the same explanation, in collagen triple-helices, it is the most abundant amino acid
• It is important to note that glycine is an inhibitory neurotransmitter
• Because of uninhibited muscle contraction, interference with its release inside the spinal cord, such as in clostridium tetani infections for
example, can trigger spastic paralysis.
Serine
• Serine is an alpha-amino acid which is often used in protein biosynthesis
• It comprises an alpha-amino group which, under biological conditions, is in the protonated -NH3
+ form
• It also contains a carboxyl group which, under biological conditions, is in the deprotonated -COO– form
• Serine is also known to contain a side chain consisting of a hydroxymethyl group and can, therefore, be classified as a polar amino acid
• Under normal physiological conditions, it can be synthesised in the human body, rendering it a nonessential aminoacid.
39. Leucine
• Leucine is an important amino acid which is used in protein biosynthesis.
• Leucine is an alpha-amino acid, which implies that it contains an alpha-amino group (which, under biological conditions, is in the protonated -
NH3
+ form), an alpha-carboxylic acid group (which, under biological conditions, is in the deprotonated -COO– form), and a side chain isobutyl
group, making it a non-polar aliphatic amino acid.
• In human beings, it is an essential amino acid, implying that it can not be synthesised by the body.
• It must, therefore, be derived from the diet.
• The foods that produce protein, such as dairy products, meats, beans, soy products, and other legumes are human dietary sources of this
amino acid
Cysteine
• Cysteine is a proteinogenic amino acid which is generally categorized as a semi-essential amino acid
• Since it functions as a nucleophile, the thiol side chain in this amino acid also participates in several enzymatic reactions
• The disulfide derivative cystine, which is known to play an essential structural role in a large number of proteins, is known to be susceptible
to oxidation by thiol
• Cysteine has the general same structure as serine, but with one of its oxygen atoms substituted by sulphur
• Selenocysteine can be obtained by replacing the same oxygen atom with selenium instead of sulfur.
• Cysteine, along with its oxidised dimeric form, cystine, like other common amino acids, can be found in most high-protein foods
• While it is listed as a non-essential amino acid, cysteine can be essential in some rare cases the elderly, for children, and people with certain
metabolic disorders or those who have syndromes of malabsorption
• Under normal physiological conditions, cysteine is normally synthesised by the human body as long as an adequate quantity of methionine is
available in it.
40. Valine
• Valine is an important amino acid which is used in protein biosynthesis
• Valine is an alpha-amino acid, which implies that it contains an alpha-amino group (which, under biological conditions, is in the protonated -
NH3
+ form), an alpha-carboxylic acid group (which, under biological conditions, is in the deprotonated -COO– form), and a side chain
containing the isopropyl group
• It can, therefore, be referred to as a non-polar aliphatic amino acid.
Most Basic Amino Acid
• There are three amino acids that have basic side chains at neutral pH.
• These are arginine (Arg), lysine (Lys), and histidine (His).
• Their side chains contain nitrogen and resemble ammonia, which is a base.
• Lysine has two amine groups, which makes it overall basic.
• It is the lone pair of nitrogen, in amines, which gives them basicity.
41. Non protein amino acids in plants
• In addition to the 20 common amino acids used for protein biosynthesis, plants also produce numerous non-
protein amino acids
• Some of these, such as l-ornithine, l-homoserine, and l-S-adenosylmethionine, are important intermediates in
primary metabolism that can be detected in most plant species
• Examples are histidine (1) in ripening bananas, arginine (2) in apple trees and some Vicia species, and proline
(3) in Caragana wood
• A few primary amino acids such as cystine (4) and trans-4-hydroxy-L-proline (5) do not occur in protein but are
synthesized secondarily from primary amino acids.
• Approximately 25–30 amino acids are involved in primary metabolism
• These primary amino acids usually occur as components of peptides or proteins and are linked by peptide bonds
or free only in small amounts, although, under unusual circumstances, free primary amino acids sometimes
accumulate in unusual quantities
• The latter of these is found in the cell wall proteins of higher plants
42. Amino acids coding for proteins
• Genetic information which is transferred from parent to offspring is the basis of inheritance
• The process begins with the replication of DNA, followed by transcription and translation
• During transcription, the genetic information stored in the DNA is copied into another form of RNA
• The whole process is governed by the complementary base pairs of the two nucleic acids
• However, the latter process of translation is not controlled by complementary but by the genetic code
• The translation is the process of converting nucleic acid information into amino acids.
Genetic Code
• The genetic code comprises the complete information of the protein manufactured from RNA
• It is the sequence of base pairs of amino acids that code for protein to be synthesized
• Thus a change in this sequence can alter the formation of amino acids
• Decoding the genetic code was a real challenge for scientists
• A physicist by name of George Gamow suggested a solution to break this challenge
• He applied the concepts of permutation and combination to decipher this genetic code
• He suggested that genetic code should be made of three nucleotides which code for 20 amino acids with four bases.
43. • Four nitrogenous bases and three nucleotides together form a triplet codon which codes for one amino acid
• Thus, the number of possible amino acids would be 4 x 4 x 4 = 64
• But we have 20 naturally existing amino acids.
This was explained by the features of the genetic code, which are as follows:
•Some amino acids are coded by more than one codon, thus making them degenerate.
•Each codon codes only for one specific amino acid.
•The codes are universal irrespective of the type of organism, i.e. CGU would code for Arginine in animals as well as in bacteria, but exceptions exist.
•Out of 64 codons, 3 are stop codons which do not code for any amino acids and thus end the process of translation.
•AUG coding for Methionine is the only codon that acts as an initiator codon.
44. WHAT ARE AMINO ACIDS
• Amino acids are organic compounds containing amine [- NH2 ] carboxyl [-COOH] side chain [R group]
• The major key elements if amino acids are carbon, hydrogen, nitrogen, oxygen.
• About 500 amino acids are known (though only 20 appear in the genetic code) and can be classified in many ways
BASIC STRUCTURE[SKELETON]
45. NEED FOR CLASSIFICATION
• Classification of amino acids gives the grouping between 20 acids and a basic outline for grouping
• It makes a clear idea to pick the amino acid type
• This is much useful for biochemists for the easy understanding between each amino acids.
Classification: Based on
R group, Polarity and R group, Distribution in protein, Nutritional requirements, Number of amino and carboxylic groups
1. Based on R-Group
• Simple amino acids: these have no functional group in their side chain. Example: glycine, valine, alanine, leucine,
isoleucine
• Hydroxy amino acids: these have a hydroxyl group in their side chain Eg: serine, threonine
• Sulfur containing amino acids: have sulfur in their side chain Eg: cysteine, methionine
• Aromatic amino acids: have benzene ring in their side chain Eg: phenylalanine, tyrosine
• Heterocyclic amino acids: having a side chain ring which possess at least one atom other than carbon Eg:
Tryptophan, histidine, proline
• Amine group containing amino acids: derivatives of amino acids in which one of carboxyl group has been
transformed into an amide group Eg: Asparagine, glutamine
• Branched chain amino acids: A branched-chain amino acid (BCAA) is an amino acid having aliphatic side-chains
with a branch Eg: leucine, isoleucine, valine
• Acidic amino acids: have carboxyl group in their side chain Eg: Aspartic and Glutamic acid
• Basic amino acids: contain amino group in their side chain Eg: Lysine, Arginine
• Imino acid: Amino acids containing a secondary amine group Eg: Proline
46. 2.Polarity and R Group
• Amino acids with non polar R group: these are hydrocarbons in nature, hydrophobic, have aliphatic and aromatic groups
[aliphatic R groups] Eg: Alanine, Valine, Leucine, Isoleucine, Proline. [Aromatic groups] Eg: Phenylalanine, Tryptophan,
Methionine(sulfur)
• Amino acids with polar but uncharged R Group: these amino acids are polar and possess neutral pH value. Eg: Glycine, Serine,
Threonine, Cysteine, Tyrosine, Glutamine, Asparagine
• Negatively charged amino acids: their side chain [R Group] contain extra carboxyl group with a dissociable proton. And render
electrochemical behaviour to proteins Eg: Aspartic acid and Glutamic acid
• Positively charged amino acid: their side chain have extra amino group Rendering basic nature to protein, Eg: Lysine, Arginine,
Histidine.
3.Distribution in protein:
• Standard protein amino acids: the amino acids that are used to form proteins, recognized by ribozyme autoaminoacylation
systems Eg: Histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
• Non standard protein amino acids: these amino acids are not required to build proteins. have a vital role as metabolic
intermediates. Eg. Hydroxyproline, Hydroxylysine, Carboxyglutamate, Diaminopimelate
• Non standard non protein amino acid: These are the derivative of amino acids and have role in metabolism. Eg: Alpha amino
butyrate, Citruline, Ornithine, beta-alanine
47. 4. Based on nutritional requirements:
• Essential amino acids: Essential amino acids cannot be made by the body. As a result, they must come from food. The essential
amino acids are: Arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine
• Non essential amino acids: An amino acid that can be made by humans and so is essential to the human diet. The
nonessential amino acids: Alanine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and
tyrosine.
5. On basis of number of amino and carboxylic groups:
Monoamino- monocarboxylic amino acids • glycine, alanine • proline • phenylalanine • methionine • serine, threonine
Monoamino-dicarboxyli amino acid: Aspartic and glutamic acid
Diamino-monocarboxylic amino acids: Lysine, arginine, histidine.
48. Properties :
Physical properties
• Colourless • Crystalline in nature • Tasteless[tyrosine], sweet[glycine, alanine] • Melting point above 200C • Soluble in polar
solvent and Insoluble in non polar solvent • Have absorbance at 280nm Mol wt: 100 – 50,000Dt • All amino acids possess
optical isomers due to the presence of asymmetric α-carbon atoms. • Some are structurally stable and sterically hindered
[Glycine] • Amino acids [proteins]posses enzymatic activities • Amino acids exhibit colloidal nature and denaturing property
Chemical properties
Decarboxylation: The amino acids will undergo decarboxylation to form the corresponding “amines”. Thus amines are produced
• Histidine → Histamine + CO2 • Tyrosine →Tyramine + CO2 • Lysine →Cadaverine + CO2
Reaction with Alkalies (Salt formation): • The carboxyl group of amino acids can release a H+ ion with the formation of
Carboxylate (COO– ) ions.
Reaction with Alcohols (Esterification): • the amino acid s is reacted with alcohol to form, “Ester”. The esters are volatile in
contrast to form amino acids.
Reaction with DANSYl Chloride: DANSYl chloride means “Dimethyl Amino Naptha Sulphonyl Chloride”. When the amino acid
reacts with DANSYl chloride reagent, it gives a “Flourescent DANSYl derivative
Reaction with acylating agents (Acylation): When the amino acids react with “Acid chloride” and acid anhydride in alkaline
medium it gives “pthaloyl amino acid
49. Reaction with Sanger’s reagent: • “1-flouro-2,4-dinitrobenzene” is called Sanger’s reagent (FDNB).sanger’s reagent reacts with
α-amino acid to produce Yellow coloured derivative, DNB-amino acid.
Reaction with Edmann’s reagent: Edmann’s reagent is “phenylisothiocyanate”. When amino acids react with Edmann’s reagent it
gives “phenyl thiohydantoic acid” finally it turns into cyclized form “Phenyl thiohydantoin” (Edmann’s derivative).
50. Structure of Proteins
• Protein structures are made by condensation of amino acids forming peptide
bonds
• The sequence of amino acids in a protein is called its primary structure
• The secondary structure is determined by the dihedral angles of the peptide
bonds, the tertiary structure by the folding of protein chains in space
• Association of folded polypeptide molecules to complex functional proteins
results in quaternary structure.
Define Protein Structure
Protein structure is defined as a polymer of amino acids joined by
peptide bonds.
Let us see how a peptide bond is established from the following reaction:
Formation of Peptide Bond
51. • We can thus see that the peptide bond (-CO-NH) is formed between the amine group of one molecule and the carboxyl group of the adjacent
molecule followed by the elimination of a water molecule
• This bond is otherwise an amide linkage
• When peptide bonds are established among more than ten amino acids, they together form a polypeptide chain
• Very often, when a polypeptide chain has a mass exceeding 10000u and the number of amino acids in the chain exceeding 100, we get a
protein.
Classification of Proteins
Based on the molecular shape, proteins can be classified into two types.
1. Fibrous Proteins:
When the polypeptide chains run parallel and are held together by hydrogen and disulfide bonds, then the fiber-like structure is formed. Such
proteins are generally insoluble in water. These are water-insoluble proteins.
Example – keratin (present in hair, wool, and silk) and myosin (present in muscles), etc.
2. Globular Proteins:
This structure results when the chains of polypeptides coil around to give a spherical shape. These are usually soluble in water.
Example – Insulin and albumins are common examples of globular proteins.
52. Levels of Protein Structure
1. Primary Structure of Protein
•The Primary structure of proteins is the exact ordering of amino acids forming their chains.
•The exact sequence of the proteins is very important as it determines the final fold and therefore the function of the protein.
•The number of polypeptide chains together form proteins
•These chains have amino acids arranged in a particular sequence which is characteristic of the specific protein
•Any change in the sequence changes the entire protein.
• The following picture represents the primary protein structure (an amino acid chain)
• As you might expect, the amino acid sequence within the polypeptide chain is crucial for the
protein’s proper functioning
• This sequence is encrypted in the DNA genetic code
• If mutation is present in the DNA and the amino acid sequence is changed, the protein function
may be affected
Primary Structure of Protein
53. • The protein ‘s primary structure is the amino acid sequence in its polypeptide chain
• If proteins were popcorn stringers designed to decorate a Christmas tree, a protein ‘s primary structure is the sequence in which various
shapes and varieties of popped maize are strung together.
• Covalent, peptide bonds which connect the amino acids together maintain the primary structure of a protein
• All documented genetic disorders, such as cystic fibrosis, sickle cell anemia, albinism, etc., are caused by mutations resulting in alterations
in the primary protein structures, which in turn lead to alterations in the secondary , tertiary and probably quarterly structure
• Amino acids are small organic molecules consisting of a chiral carbon with four substituents.
• Of those only the fourth the side chain is different among amino acids.
54. Secondary Structure of Protein
Secondary structure of protein refers to local folded structures that form within a polypeptide due to interactions between atoms of
the backbone.
•The proteins do not exist in just simple chains of polypeptides.
•These polypeptide chains usually fold due to the interaction between the amine and carboxyl group of the peptide link.
•The structure refers to the shape in which a long polypeptide chain can exist.
•They are found to exist in two different types of structures α – helix and β – pleated sheet structures.
•This structure arises due to the regular folding of the backbone of the polypeptide chain due to hydrogen bonding between -CO
group and -NH groups of the peptide bond.
•However, segments of the protein chain may acquire their own local fold, which is much simpler and usually takes the shape of a
spiral an extended shape or a loop
•These local folds are termed secondary elements and form the proteins secondary structure
α – Helix:
• α – Helix is one of the most common ways in which a polypeptide chain forms all possible hydrogen bonds by twisting into a right-handed screw with the -NH
group of each amino acid residue hydrogen-bonded to the -CO of the adjacent turn of the helix.
• The polypeptide chains twisted into a right-handed screw.
β – pleated sheet:
• In this arrangement, the polypeptide chains are stretched out beside one another and then bonded by intermolecular H-bonds
• In this structure, all peptide chains are stretched out to nearly maximum extension and then laid side by side which is held together by intermolecular hydrogen
bonds
55. Tertiary Structure of Protein
•This structure arises from further folding of the secondary structure of the protein.
•H-bonds, electrostatic forces, disulphide linkages, and Vander Waals forces stabilize this structure.
•The tertiary structure of proteins represents overall folding of the polypeptide chains, further folding of the
secondary structure.
•It gives rise to two major molecular shapes called fibrous and globular.
•The main forces which stabilize the secondary and tertiary structures of proteins are hydrogen bonds,
disulphide linkages, van der Waals and electrostatic forces of attraction.
4. Quaternary Structure of Protein
• The spatial arrangement of various tertiary structures gives rise to the quaternary structure
• Some of the proteins are composed of two or more polypeptide chains referred to as sub-units
• The spatial arrangement of these subunits with respect to each other is known as quaternary structure.
56. • The exact amino acid sequence of each protein drives it to fold into its own unique and biologically active three-dimensional fold also known
as the tertiary structure
• Proteins consist of different combinations of secondary elements some of which are simple whereas others are more complex
• Parts of the protein chain, which have their own three-dimensional fold and can be attributed to some function are called “domains”
• These are considered today as the evolutionary and functional building blocks of proteins
• Many proteins, most of which are enzymes contain organic or elemental components needed for their activity and stability
• Thus the study of protein evolution not only gives structural insight but also connects proteins of quite different parts of the metabolism.
57. Rules of Protein Structure
•The type determines the function of a protein.
•A protein’s shape is determined by its primary structure (the amino acid sequence).
•The amino acid sequence within a protein is determined by the encoding sequence of nucleotides in the gene (DNA).
Summary of Protein Structure
• Linderstrom-Lang (1952) in particular first suggested a hierarchy of protein structure with four levels: central, secondary, tertiary , and
quaternary
• The primary structure of protein is the hierarchy’s basic level, and is the particular linear sequence of amino acids comprising one
polypeptide chain
• Secondary structure is the next level up from the primary structure, and is the regular folding of regions into specific structural patterns
within one polypeptide chain
Hydrogen bonds between the carbonyl oxygen and the peptide bond amide hydrogen are normally held together by secondary structures
• Tertiary structure is the next level up from the secondary structure, and is the particular three-dimensional arrangement of all the amino
acids in a single polypeptide chain
This structure is usually conformational, native, and active, and is held together by multiple noncovalent interactions
• Quaternary structure is the next ‘step up’ between two or more polypeptide chains from the tertiary structure and is the specific spatial
arrangement and interactions.
58. Frequently Asked Questions – FAQs
What makes up protein structure?
A protein’s primary structure refers to the amino acid sequence in the polypeptide chain. Peptide bonds that are made during the protein biosynthesis process hold the primary structure
together.
What are the 4 stages of protein structure?
Four levels of structure of proteins. The principal, secondary, tertiary and quaternary levels of protein structure are the four stages. To fully understand how a protein functions, it is
helpful to understand the purpose and role of each level of protein structure.
What is the process of protein folding?
The folding of proteins is the mechanism through which a protein structure assumes its functional shape or conformation. Both molecules of protein are heterogeneous unbranched
amino acid chains. They may perform their biological function by coiling and folding in a particular three-dimensional shape.
How proteins are formed?
Amino acids form a polypeptide, In another words when amino acids bound by a sequence of peptide bonds , leads to formation of proteins. The polypeptide then folds into a particular
conformation based on the interactions (strained lines) between its side chains of amino acids.
Is DNA a protein?
DNA is often associated with proteins in the nucleus called histones, but DNA itself is not a protein. No. DNA is a nucleic acid consisting of phosphate and sugar groups, bases ( purines
and pyrimidines), while proteins are large molecules made up of one or more long amino acid chains.
What stabilizes protein structure?
Hydrogen bonding in the polypeptide chain and between amino acid “R” groups helps to preserve protein structure by keeping the protein in the form formed by the
hydrophobic interactions. What is called a disulfide bridge is formed by this sort of bonding.
What determines protein structure?
In the polypeptide chain, the main structure of a protein relates to the amino acid sequence. The primary structure is bound together by peptide bonds that are
made during the phase of protein biosynthesis. The primary structure of a protein is determined by the gene corresponding to the protein.
What is the primary structure of a protein?
The linear sequence of amino acids within a protein is called the primary structure of the protein. A sequence of just twenty amino acids, each of which has a special
side chain, is made up of proteins. The side chains of amino acids are chemically distinct.
59. Amino acids and their derivatives have various prominent functions in plants, such as protein synthesis, growth
and development, nutrition and stress responses
60. Unit - VIII Metabolic Pool and Secondary Metabolites
Introduction
• The metabolism can be defined as the sum of all the biochemical reactions carried out by an organism
• Metabolites are the intermediates and products of metabolism and are usually restricted to small
molecules
• The term “secondary” introduced by A. Kossel in 1891 implies that while primary metabolites are present
in every living cell capable of dividing, the secondary metabolites are present only incidentally and are
not of paramount significance for organism’s life
• Though secondary metabolites are derived from primary metabolism, they do not make up basic
molecular skeleton of the organism
• Its absence does not immediately curtail the life of an organism, a feature contrary to primary metabolite,
but survival of the organism is impaired to a larger extent
• Its presence and synthesis are observed in ecologically disadvantaged species within a phylogenetic
group
• The difference between primary and secondary metabolite is ambiguous since many of the
intermediates in primary metabolism is overlapping with the intermediates of secondary metabolites
• Amino acids though considered a product of primary metabolite are definitely secondary metabolite too
• Contrary to the observation that sterols are secondary metabolites that are indispensable part of many
structural framework of a cell
• The mosaic nature of an intermediate indicates common biochemical pathway being shared by primary
61. • The secondary metabolites serve as a buffering zone into which excess C and N can be shunted into to
form inactive part of primary metabolism
• The stored C and N can revert back to primary metabolite by the metabolic disintegration of secondary
metabolite when on demand
• There is dynamism and a delicate balance between the activities of the primary and secondary
metabolism being influenced by growth, tissue differentiation and development of the cell or body, and
also external pressures
• Hence, secondary metabolites or natural products can be defined as a heterogeneous group of natural
metabolic products that are not essential for vegetative growth of the producing organisms, but they are
considered differentiation compounds conferring adaptive roles, for example, by functioning as defense
compounds or signaling molecules in ecological interactions, symbiosis, metal transport, competition,
and so on
• The multitude of secondary metabolite secretions is harvested by human kind to improve their health
(antibiotics, enzyme inhibitors, immunomodulators, antitumor agents, and growth promoters of animals
and plants), widen the pyramid of healthy nutrition (pigments and nutraceuticals), enhancing agricultural
productivity (pesticides, insecticides, effectors of ecological competition and symbiosis and
pheromones), and hence impacting economics our society in a certain positive way
• They are a source of antibiotics.
63. Classification of secondary metabolites
• Over 2,140,000 secondary metabolites are known and are commonly classified according to their vast diversity in
structure, function, and biosynthesis
• There are five main classes of secondary metabolites such as terpenoids and steroids, fatty acid-derived
substances and polyketides, alkaloids, non ribosomal polypeptides, and enzyme cofactors
1. Terpenoids and steroids
• They are major group of substances derived biosynthetically from isopentenyl diphosphate
• Currently, over 35,000 known terpenoid and steroid compounds are identified
• Terpenoids have different variety of unrelated structures, while steroids have a common tetracyclic carbon skeleton
and are modified terpenoids that are biosynthesized from the triterpene lanosterol.
2. Alkaloids
• There are over 12,000 known compounds of alkaloids, and their basic structures consist of basic amine group and
are derived biosynthetically from amino acids
3. Fatty acid-derived substances and polyketides
• Around 10,000 compounds are identified and are biosynthesized from simple acyl precursors such as propionyl
CoA, acetyl CoA, and methyl malonyl CoA
4. Non ribosomal polypeptides
• These amino acids derived compounds are biologically synthesized by a multifunctional enzyme complex without
direct RNA transcription.
5. Enzyme cofactors
• Enzyme cofactors are nonprotein, low-molecular enzyme component
64. Functions of secondary metabolites
The major functions of the secondary metabolites including antibiotics are:
1.competitive weapons against other livings such as animals, plants, insects, and microorganisms
2.metal transporting agents
3.agents for symbiotic relation with other organisms
4.reproductive agent and
5.differentiation effectors
6.agents of communication between organisms
• The other functions include interference in spore formation (not obligatory) and germination
• Predominantly, the secondary metabolites are used for variety of biological activities like antimicrobial and
antiparasitic agents, enzyme inhibitors and antitumor agent, immunosuppressive agents, etc.
Sources of secondary metabolites
• The major sources of secondary metabolites are plants (80% of secondary metabolite), bacteria, fungi, and many
marine organisms (sponges, tunicates, corals, and snails)
65. Secondary metabolites of plants
• Plant secondary metabolites represent highly economically valuable products
• These are used as high value chemicals such as drugs, flavors, fragrances, insecticides, dyes, etc
• Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been
found to have in vitro antimicrobial properties
• Plants have an almost limitless ability to synthesize aromatic substances, most of which are phenols or their oxygen-substituted
derivatives
• About 25,000 terpenoids are known as secondary compounds and are derived from the five-carbon precursor isopentenyl
diphosphate (IPP)
• In total, around 12,000 known alkaloids are identified, and they possess one or more nitrogen atoms which are biosynthesized
from amino acids
• The 8000 known phenolic compounds are synthesized either through the shikimic acid pathway or through the malonate/acetate
pathway
• Many alkaloids are used in medicine, usually in the form of salts
• Some examples include vinblastine which has antitumor properties; quinine which has antipyretics and antimalarial properties; and
reserpine which can be used to treat high blood pressure
• Alkaloids are regarded as reserve materials for protein synthesis, as protective substances discouraging animal or insect attacks,
and as plant stimulants or regulators or simply as detoxification products
• Alkaloids currently in clinical use include the analgesics morphine and codeine, the anticancer agent vinblastine, the gout
66. • In vitro studies have shown that natural phenols have antimicrobial, antiviral, anti-inflammatory, and vasodilatory actions
• It protects the plant against adverse factors which threaten its survival in an unfavorable environment, such as drought, physical
damage or infections
• Resistance of plants to UV radiations is due to the phenolic compounds especially the phenylpropanoids present in them
• Phenolic compounds act as antioxidants protecting cells from oxidative stress scavenging of free radicals by hydrogen atom
donation
• The action of phenolic as neuroprotective, fungicidal, bactericidal compounds and their anti-atherosclerosis effects, and
anticancer activity is well documented
• Terpenoids are commercially important fragrance and flavoring agents
• Prenol and α-bisabolol are used in fragrance due to fruity odor and sweet floral aroma, respectively
• Mono and sesqui terpenes are basis of natural perfumes and also of spices and flavorings in the food industry
• The roles of terpenoids as pharmaceutical agents with activities such as antibacterial and antineoplastic are still under
investigation
• There are examples of diterpenes that exhibited in vitro cytotoxic, antitumor, and antimicrobial activities
• Terpenes are vital for life in most organisms exerting metabolic control and mediating inter and intra species interactions, for
example, manufacture compounds in response to herbivory or stress factors, and it has also been shown that flowers can emit
terpenoids to attract pollinating insects and even attract beneficial mites, which feed on herbivorous insects
• terpenes may act as chemical messengers influencing the expression of genes involved in plant defensive functions or influence
69. Production of secondary metabolites from plants
1. Conventional
• The conventional method of secondary metabolite production relies on extraction of metabolite, not production,
from the tissues of plant by different phytochemical procedures like solvent, steam, and supercritical extraction
• The recent developments in biotechnological methods like plant tissue culture, enzyme and fermentation
technology have facilitated in vitro synthesis and production of plant secondary metabolites
• The major processes include:
Immobilization
• Cell or biocatalysts are confined within a matrix by entrapment, adsorption or covalent linkage
• On addition of suitable substrate and provision on optimum physico chemical parameters, the desired secondary
metabolites are synthesized
• Immobilization with suitable bioreactor system provides several advantages, such as continuous process operation,
but for the development of an immobilized plant cell culture process, natural or artificially induced secretion of the
accumulated product into the surrounding medium is necessary.
70. In vitro tissue, organ, and cell culture
• Plant cell and tissue cultures can be established routinely under sterile conditions from explants, such as plant
leaves, stems, roots, meristems, etc., both for multiplication and extraction of secondary metabolites
• Shoot, root, callus, cell suspension, and hairy root culture are used to synthesize metabolite of interest
• Metabolites which are localized in multiple tissues can be synthesized through unorganized callus or suspension
cultures
• But when the metabolite of interest is restricted to specialized part or glands in host plant, differentiated microplant
or organ culture is the method of choice
• Saponins from ginseng are produced in its roots, and hence in vitro root culture is preferred for saponin synthesis
• Similarly, antidepressant hypericin and hyperforin are localized in foliar glands of Hypericum perforatum, which
have not been synthesized from undifferentiated cells
71. • The quantum of secondary metabolite production in cell cultures can be enhanced by treating plant cells with biotic
and/or abiotic elicitors (foreign molecules attached to receptors)
• Methyl jasmonate, fungal carbohydrates, and yeast extract are the commonly used elicitors
• Methyl jasmonate is an established and effective elicitor used in the production of taxol from Taxus chinensis and
ginsenoside from Panax ginseng
• The most recently evolved and designed metabolic engineering can be employed to improve the productivity
• The production of metabolites through hairy root system based on inoculation with Agrobacterium rhizogenes has
garnered much attention of late
• The quality and quantity of secondary metabolite by hairy root systems is same or even better than the synthesis by
intact host plant root
• In addition, stable genetic make up, instant growth in plant tissue culture media and phytohormones provides
additional scope for biochemical studies
• Root tips infected with A. rhizogenes are grown on tissue culture media [Murashige and Skoog’s (MS) Gamborg’s
B5 or SH media] lacking phytohormones
• Srivastava and Srivastava have recently summarized the attempts to adapt bioreactor design to hairy root cultures;
stirred tank, airlift, bubble columns, connective flow, turbine blade, rotating drum, as well as different gas phase
reactors have all been used successfully
72. Secondary metabolites of microorganisms
• Microbial secondary metabolites are low molecular mass products with unusual structures
• The structurally diverse metabolites show a variety of biological activities like antimicrobial agents, inhibitors of
enzymes and antitumors, immune-suppressives and antiparasitic agents, plant growth stimulators, herbicides,
insecticides, antihelmintics
• They are produced during the late growth phase of the microorganisms
• The secondary metabolite production is controlled by special regulatory mechanisms in microorganisms, as their
production is generally repressed in logarithmic phase and depressed in stationary growth phases
• The microbial secondary metabolites have distinctive molecular skeleton which is not found in the chemical libraries
and about 40% of the microbial metabolites cannot be chemically synthesized
Features of microbial secondary metabolites
•The principle and process of natural fermentation product synthesis can be successfully scaled up and employed to
maximize its application in the field of medicine, agriculture, food, and environment
•The metabolite can serve as a starting material for deriving a product of interest, extended further through chemical or
biological transformation
73. Applications of microbial secondary metabolites
Antibiotics
• The discovery of penicillin initiated the researchers for the exploitation of microorganisms for secondary metabolite
production, which revolutionized the field of microbiology
• With the advent of new screening and isolation techniques, a variety of β-lactam-containing molecules and other
types of antibiotics have been identified
• About 6000 antibiotics have been described, 4000 from actinobacteria
• In the prokaryotic group, unicellular bacteria Bacillus and Pseudomonas species are the most recurrent antibiotic
producers
• Likewise in eukaryotes, fungi are dominant antibiotic producers next to plants
• In the recent years, myxobacteria and cyanobacteria species have joined these distinguished organisms as
productive species.
74. Metabolic pool refers to the reservoir of molecules upon which enzymes can operate
Explanation:
• The concept of metabolic pools is important to cellular biology
• Metabolic pools consist of metabolites that are products of/and or the substrates for key reactions in cells, allowing
one type of molecule to be changed into another type such as carbohydrates converted into fats
• Within a cell (or an organelle like chloroplast) there exists a reservoir of molecules upon which an enzyme can
operate
• The size of the reservoir is referred to as its metabolic pool
• For example glycolysis and the Kreb's cycle are open systems
• An open system has a two way flow of materials into and out of it:
a) various compounds enter the pathways at different points. Thus carbohydrates, fats, and proteins can all be
oxidised.
b) at the same time, some of the intermediate of these pathways can be withdrawn. They are used in synthesis
reactions.
Thus, the products of glycolysis and the Kreb's cycle form a metabolic pool. The materials can be added or
withdrawn from this pool according to the need of the body.
75. What is Metabolism?
• Metabolism is defined as the total amount of the biochemical reactions involved in maintaining the living conditions of the cells in an
organism
• All living organisms require energy for different essential processes and for producing new organic substances
• The entire process of nutrition has two main parts- ingestion of food and utilization of food for energy
• In every living organism, let it be a simple prokaryotic bacterial cell or a eukaryotic cell, the process of nutrition is the same
• The concept of metabolic reactions concentrates on the utilization of food for energy
• Ingested food needs to be utilized for the turnover
• The nutrition is the key and energy extraction is the target of metabolism
76. Concept of Metabolism
How does a cell extract energy and how does it synthesize the building blocks of its macromolecules?
• Metabolism is the sum total of all the chemical reactions taking place in the cells of the living organisms
• This involves both breaking and making of biomolecules
• Catabolism and anabolism are two types of metabolism
• Catabolism (breaking of bonds) involves the breaking of biomolecules while anabolism (making of bonds) is the building of new
compounds required by the cells
• The food which we eat happens to be useless until and unless it undergoes metabolic changes
• During metabolism, biomolecules present in the food get utilized to extract the energy from the cell
• In addition, conversion and formation of the biomolecules take place
• In other words, the transformation of one compound results in the formation of another molecule
• For example, the proteins we obtained from the food are metabolized into amino acids, which are later utilized to synthesize another
protein required by the cell
• All metabolic changes take place in multiple reactions and follow a particular pathway called the metabolic pathway
• The metabolic pathway includes a series of reactions
77. • The metabolite flow, the rate, and direction at which metabolism takes place are called the dynamic state of body constituents
• All metabolic reactions are catalyzed by a set of proteinaceous compounds called enzymes.
• Hence, metabolism is an enzyme-catalyzed reaction which provides biomolecules, needed by the cells for growth, maintenance, and repair
etc
Let us summarize the purposes of metabolic pathways in the below three points:
To extract energy from the food for cellular activities
To convert food to building blocks, to synthesize biomolecules such as carbohydrates, proteins, lipids and nucleic acids
To eliminate waste and toxic products.
