The document covers the structure and classification of carbohydrates, emphasizing the differences between monosaccharides, oligosaccharides, and polysaccharides, as well as their roles in energy storage and cellular structure. It also discusses lipids, detailing their functions as storage and signaling molecules, the structure of fatty acids, and the role of complex lipids in cell membranes. Additionally, it addresses cell signaling mechanisms and the importance of signal transduction pathways in cellular communication and disease progression.

1. Unit 5 Objectives
• Identify the elements that make up Carbohydrates
• understand classification and structure of Carbohydrates
• understand different classes of Carbohydrates
• Differentiate between simple and complex Carbohydrates

2. 5.Carbohydrates
 Carbohydrate is a common class of simple organic compounds
 Hydrated carbons with general formula
(where x is an integer)
It is an aldehyde or a ketone that has additional hydroxyl groups:
 Polyhydroxy Aldehyde or Polyhydroxy Ketones or compounds that can be hydrolyzed
into those compounds
Functions of Carbohydrates
 Serve as substrate for energy in most organisms
 Give structure to cell membranes and cell walls (in plants)
 Serve as metabolic intermediates
 Components of Nucleotides and Nucleic Acids (DNA and RNA)

3. 5.1. Monosaccharide
Monosaccharides (Simple Sugars)
Are the simplest carbohydrates
Have basic structure (C·H2O)n, where n is three or
greater
Cannot be hydrolyzed any further (e.g., Glucose,
Galactose, and Fructose)
Monosaccharides link to each other through
glycosidic bond to form other groups

5. Cont…
Variations between monosaccharides
Two major groups based on the type of carbonyl
functional group (reactive group)
• Aldose: Monosaccharides that contain Aldehyde (-
CHO) functional group (e.g., Glucose)
• Ketose: Monosaccharides that contain Ketone
(=C=O) functional group (e.g., Fructose)

6. Conti…

7. Cont…
Naming of monosaccharides
 By convention, the letters ‘ose’ at the end of a biochemical name flags a molecule
as a sugar. Thus, there are glucose, galactose, sucrose, and many other ‘-oses’.
 Names form by adding suffix – ose to prefix that indicates the Number of Carbon
Atoms in the Monosaccharide
Examples:
Monosaccharide containing
 3 Carbon atoms is called a Tri-ose
 4 Carbon atoms >>a Tetr-ose
 5 Carbon atoms >> Pent-ose
 6 carbon atoms >> Hex-ose,
 Carbon atoms in Monosaccharide are numbered sequentially, with the Carbon
containing the Functional (Carbonyl) group having the lowest possible number

8. Cont…
 Further, prefix Aldo- or Keto- will be added to indicate the Carbonyl
Functional Group
The presence of aldehyde functional group as the first carbon atom, we will
write as follows
 Aldo-triose,
 Aldo-tetrose
 Aldo-pentose
 Aldo-hexose

10. Cont…
To denote the presence of the Ketone functional group as the
second carbon atom
Keto-triose
Keto-tetrose
Keto-pentose
Keto-hexose
Three-carbon sugars (Triose sugars) are the smallest
carbohydrates
Glyceraldehyde (an Aldotriose) and
Dihydroxyacetone (a Ketotriose

11. Cont…

16. Cont…
Reducing sugars
 Monosaccharides (simple sugars) like glucose are reducing sugars
 Reducing sugars are those that can:
 Reduce Cu2+ ions to Cu+ ions (Fehling’s solution) or
 Give Positive Silver Mirror Test by reducing Ammonical Silver (1) Nitrate to Metallic Silver
(Tollen’s reagent)
 Reducing property is due mainly to the presence in the sugar of Aldehyde group that is
oxidized to a Carboxylic Acid group
>>Aldose sugars have greater reducing powers than Ketose sugars
 That is, Fehling’s solution and Tollen’s reagent are not normally affected by Ketone
 In an alkaline medium, however, ketose sugars example, fructose form an aldos sugar
(glucose) and able to reduce Fehling’s solution and Tollen’s reagent
 In an acidic medium however, the reverse reaction occurs

17. 5.2. Oligosaccharides
Formed from two monosaccharides linked through
glycosidic bond
Disaccharides of physiological importance include:
Maltose
Is a malt sugar formed from two units of glucose
Sucrose
 formed from glucose and fructose
Lactose
Formed from galactose and glucose
Found in milk

18. Cont…
Sucrose, lactose, and maltose
•Maltose hydrolyzes to 2 molecules of
D-glucose
•Lactose hydrolyzes to a molecule of
glucose and a molecule of galactose
•Sucrose hydrolyzes to a molecule of
glucose and a molecule of fructose

19. 5.3. Polysaccharides
 Polysaccharides, as their name implies, are made by
joining together many sugars
 The functions of polysaccharides are varied
 They include energy storage, structural strength, and
lubrication
 Polysaccharides involved in energy storage include the
plant polysaccharides, amylose and amylopectin
 The polysaccharide involved in energy storage in animals
is glycogen and it is mostly found in the muscles and liver

20. Cont…
Polysaccharides vary in:
 Monomeric composition
 Type of glycosidc bond connecting the monosaccharide units
 Chain length and degree of branching, and
 Biological function
Homo-polysaccharides consist of only one type of monosaccharide linked
by glycosidic bonds
When the repeating unit is:
 Glucose, the homo-polysaccharide is Glucan or Glucosan
 Galactose >> Galactan
 Fructose >> Fructosan
Example of homo-polysaccharide: Starch, Glycogen, Cellulose

21. Cont…
Starches
 Major storage form of Glucose in most plants
 Two main constituents of starch are Amylopectin and Amylose
 Amylose is the simplest of the polysaccharides, being comprised solely of glucose units
joined in an alpha 1-4 linkage.
 Amylose is broken down by the enzyme alpha-amylase, found in saliva
 Amylopectin is related to amylose in being composed only of glucose, but it differs in
how the glucose units are joined together
 Alpha 1-4 linkages predominate, but every 30-50 residues, a ‘branch’ arises from an
alpha 1-6 linkage.
 Such branches make the structure of amylopectin more complex than that of
amylose.

23. Cont…
Glycogen
Glycogen is a polysaccharide that is physically
related to amylopectin in being built only of
glucose and in having a mix of alpha 1-4 and alpha
1-6 bonds.
Glycogen, however, has many more alpha 1-6
branches than amylopectin, with such bonds
occurring about every 10 residues.

24. Amylopectin

25. Cont…
Cellulose
 It is a polymer of glucose used to give plant cell walls structural integrity
and has the individual units joined solely in a beta 1-4 configuration
 That simple structural change makes a radical difference in its
digestibility
 Humans are unable to break down cellulose and it passes through the
digestive system as roughage
 Ruminant animals, such as cattle, however have bacteria in their rumens
that contain the enzyme cellulase
 It breaks the beta 1-4 links of the glucoses in cellulose to release the
sugars for energy

27. 5.4. Glycoconjugates
 Glycoconjugates are essential in living things.
 Glycosylation is a process that forms glycoconjugates.
 involved in cell to cell communications, such as cell-cell
recognition.
 They are also essential in long term immune protection.
 Examples of glycoconjugates are
 glycoproteins,
 glycopeptides,
 peptidoglycans,
 glycosides,
 glycolipids, and
 lipopolysaccharides

28. Unit 6: Objectives
Describe the Lipids
Differentiate Storage lipids, Lipids as signal, cofactors and
pigments.
Explain how Working with lipids, Signal transduction
pathways.
Describe Basic Elements of Cell Signaling Systems.
Explain Role of Second Messengers
,

29. Lipids
 Soluble in non-polar organic solvents
 Contain C, H, O
 Sometimes N & P
 Includes fats and oils – mostly triglycerides
 Fat: solid at room temperature
 Oil: liquid at room temperature
 More highly reduced than CHO
 more energy

30. Cont…
 Concentrated source of energy (9 kcal/gm)
 Energy reserve: any excess energy from
carbohydrates, proteins and lipids are stored as
triglycerides in adipose tissues
 Provide insulation to the body from cold
 Maintain body temperature
 Mechanical insulation
 Protects vital organs
 Electrical insulation
 Protects nerves, help conduct electro-chemical
impulses (myelin sheath)
 Supply essential fatty acids (EFA)

Linoleic acid and linolenic acid

31. Cont…
 Formation of cell membranes
 Phospholipids, a type of fat necessary for the synthesis
of every cell membrane (also glycoproteins and
glycolipids)
 Synthesis of prostaglandins from fatty acids
 Hormone-like compounds that modulates many
body processes

Immune system, nervous systems, and GI secretions

Regulatory functions: lower BP, blood clotting, uterine
contractions
 Help transport fat soluble vitamins
 Palatability and aroma
 Flavor and taste for some species!
 The satiety value – help control appetite
 Fullness; fats are digested slower

33. Conti..

34. Fatty Acid Structure

35. 6.1.Fatty Acids (Storage lipids)
 Building blocks for triglycerides and
phospholipids

37. Cont…
 Short chain: 2 to 6 C (volatile fatty acids)
 Medium chain: 8 – 12 C
 Long chain: 14 – 24 C
 As chain length increases, melting point
increases
 Fatty acids synthesized by plants and animals
have an even number of carbons
 Mostly long chain
 16C to 18C fatty acids are most prevalent

38. Fatty Acid Saturation
 Saturated - no double bonds
 Unsaturated – contain double bonds
 Monounsaturated – one double bond
 Polyunsaturated - >1 double bond
 The double bond is a point of
unsaturation
 As number of double bonds increases,
melting point decreases

39.  What are Essential Fatty Acids
And their Functions ?

40. Triacylglycerols
 Triacylglycerols are the primary storage form of long-chain fatty
acids.
 which are broken down for energy and used in the structural
formation of cells.
 Triacylglycerols are composed of glycerol (1,2,3-
trihydroxypropane) and 3 fatty acids to form a triester.
 Triacylglycerols are stored in adipocytes in vertebrates or as soils in
the seed of plants.
 The simplest lipid.

41. Conti…
1.Why do animals that live in cold climates
generally have more polyunsaturated fatty acid
residues in their fats than do animals that live
in warm climates?

43. Complex cell membrane lipids
Structural lipids
• Amphipathic molecules
– Polar head group and hydrophobic tail
• Bilayer: hydrophobic effect and van der Waals interaction
• Classes:
– phosphoglycerides
– sphingolipids
– Steroids
• Difference: 1. chemical structure, 2. abundance, and
3. function

44. sphingolipids
• Derived from sphingosine:
– an amino alcohol with a long hydrocarbon chain
– a long-chain fatty acid attached to the sphingosine amino
group
• eg. Sphingomyeline (SM): phosphocholine is attached to the
terminal hydroxyl group of sphingosine
• Amphipathic glycolipids: polar head groups are sugars
(GlcCer)

45. • Phospholipid bilayers
– The hydrocarbon chains of the phospholipids
• Properties:
– an impermeable barrier
• prevents the diffusion of water-soluble
(hydrophilic) solutes across the membrane
– Stability maintain
• By hydrophobic and van der Waals interaction
between the lipid chains

47. Cont….
glycerol – a 3-carbon polyalcohol acting as a backbone
for the phospholipids
2 fatty acids attached to the glycerol
phosphate group attached to the glycerol

48. Cont…
• Glycolipids are lipids with a carbohydrate
attached by a glycosidic bond.
• Their role is to maintain the stability of the cell
membrane and to facilitate cellular recognition,
which is crucial to the immune response and in
the connections that allow cells to connect to
one another to form tissues

49. Cnti…
• Cholesterol acts as a bidirectional regulator of membrane fluidity
because at high temperatures, it stabilizes the membrane and
raises its melting point, whereas at low temperatures it intercalates
between the phospholipids and prevents them from clustering
together and stiffening.
• This helps slightly immobilize the outer surface of the membrane
and make it less soluble to very small water-soluble molecules that
could otherwise pass through more easily. Without cholesterol, cell
membranes would be too fluid, not firm enough, and too
permeable to some molecules.
• At higher temperatures, lipid bilayers become more fluid (think
about butter melting on a hot day), and more permeable or
leaky. ... In mammals, cholesterol increases membrane packing to
reduce membrane fluidity and permeability. The fatty acids tails of
phospholipids also affect membrane fluidity.

52. Sterols
 Sterols are comprised of tetracyclic rings.
 Sterols can be conjugated to fatty acids, fatty acid esters, and
sugars.
 Sterols have a fundamental effect in membrane properties.
 They affecting fluidity, membrane transport and function of
membrane proteins.

53. 6.2.Lipids as signal, cofactors and pigments
lipids, present in much smaller amounts, have
active roles in the metabolic traffic as metabolites
and messengers.
 Some serve as potent signals—as hormones,
carried in the blood from one tissue to another.
as intracellular messengers generated in response
to an extracellular signal.

54. Cont..
 Others function as enzyme cofactors in electron-transfer reactions in
chloroplasts and mitochondria.
 Other group of lipids with a system of conjugated double bonds:
pigment molecules that absorb visible light.
 Some of these act as light-capturing pigments in vision and photo-
synthesis; others produce natural colorations.
 Prostaglandins,
 Thromboxanes
 Steroid hormones
 Sphingosine

55. 6.3. Working with lipids
Lipids are immiscible in water.
 organic solvents are used to extract and fractionate
lipids from a mixture of lipids.
 The source of lipids could be a cell or a tissue from
an organism.
 Extraction of lipids using organic solvents.

56. Cont…
After extraction, the separation of lipids is done by
different methods based on the polarity or solubility.
 Not all but some types of lipids are more prone to
degradation by enzymes or under certain conditions.
These conditions are also made use of to generate
simple lipids from compound lipids.

58. 6.4. Signal transduction pathways
 Cell signaling is defined as the communication procedure
which coordinates the various processes by cellular
communications.
 The cell senses extra cellular signals: – Hormones,
pheromones, heat, cold, light, osmotic pressure,
concentration change of glucose, K + , Ca2+ or cAMP.
 commutes them in intracellular signals: – Signalling
involves the same type of molecular modification as
metabolism: production and degradation of substances,
phosphorylation, activation of inhibition of reactions.

60. Cont…
Any fault in cell signaling interactions or
information processing leads to disease
progression such as cancer, or diabetes.
Therefore, diseases may be treated more
effectively by understanding its molecular
cascades or cell signaling pathway
What’s the difference Metabolism and Signal
Transduction?

61. Characteristics of Signal Transduction

62. 6.4.1. Gated ion channels
 Gated ion channels are proteins that form pores in cell membranes,
allowing ions to pass through in response to specific signals.
 These channels can be classified based on the stimulus that opens them:
1. Voltage Gated Ion Channels: Open in response to changes in
membrane potential.
2. Ligand-Gated Ion Channels: Open when a specific molecule (ligand)
binds to the channel.
3. Mechanically-Gated Ion Channels: Open in response to mechanical
forces such as stretch or pressure.
 These channels play vital roles in processes such as nerve impulse
transmission, muscle contraction, and cellular homeostasis.

63. 6.4.2. Receptors and secondary messengers
 RECEPTORS
 Different types of cells possess different types of receptors.
 which bind and recognize different ligands.
 G protein-coupled receptors (GPCRs)
 Enzyme linked receptors
 Ligand-gated channels
 Steroid hormone receptors
 Gate ion channel
 Signaling molecules/ligands like hormones or neurotransmitters
reach to the cell and bind to their specific receptors.
 Then second messengers are the molecules which are present
in the cell cytoplasm act to trigger a response.

64.  Second messengers act as chemical relays from the plasma
membrane into the cytoplasm for intracellular signal
transduction.
 Examples of second messenger molecules include cyclic
AMP, cyclic GMP, inositol trisphosphate, diacylglycerol, and
calcium.

65. 6.4.3. Protein phosphorylation and dephosphorilation
Phosphorylation and dephosphorylation are crucial regulatory
mechanisms in signal transduction:
1. Protein Kinases:
 Enzymes that transfer phosphate groups from ATP to specific amino
acids (serine, threonine, or tyrosine) on target proteins.
 This process often activates or deactivates the protein's function.
2. Protein Phosphatases:
 Enzymes that remove phosphate groups from proteins.
 reversing the action of kinases and thereby modulating the Protein's
activity.

67. 6.4.4. Defects in signaling pathways and its relation to cancer
•Defects or dysregulation in signaling pathways can lead to
uncontrolled cell growth and cancer.
Examples include:
1. Oncogenes: Mutated or overexpressed genes that promote cell
proliferation (e.g., mutated Ras proteins).
2. Tumor Suppressors: Genes that normally inhibit cell division and
promote apoptosis, which can lead to cancer when inactivated .
3. Signaling Pathway Mutations: Alterations in pathways can drive
oncogenesis.

68. 6.4.5. Signal transduction in microorganisms
 microorganisms respond to specific signals from
their environment and from other organisms.
 The organisms generally respond to these changes
by modulating their metabolic potential and gene
expression.
 They have mechanisms that allow them to sense the
density of members of their own species or in the
case of parasites
 symbionts of appropriate host organisms.
 micro-organisms can undergo extensive
morphological and physiological
change, eg sporulation or lateral flagella formation.

69. Cont…
They can modify their own environment, for
example, by growing in microbial mats to allow for
efficient nutrient utilization.
How do micro-organisms detect environmental
change?
How do they integrate environmental information
to generate an appropriate response?
 How do these mechanisms evolve so that they can
be adapted to the ecological strategy of specific
organisms?

70. 7. Central metabolic pathways and energy transduction(OBJECTIVES)
• Define
• Describe
• Explain
• Differentiated

71. 7.1.Bioenergetics
Bioenergetics is the study of the flow and transformation of
energy in living organisms.
 It involves understanding how cells extract energy from their
environment.
 How this energy is utilized to perform biological work.
 First Law of Thermodynamics: Energy cannot be created or
destroyed, only transformed from one form to another.
 Second Law of Thermodynamics: The entropy (disorder) of the
universe always increases in spontaneous processes.

73. Types of metabolism

74. 7.2. Phosphoryl group transfer and ATP
 ATP (adenosine triphosphate) is the primary energy currency of the
cell.
 It provides energy for various cellular processes through the transfer of
its high-energy phosphoryl groups.
1. ATP Structure: ATP consists of an adenine base, ribose sugar, and
three phosphate groups.
2. Phosphoryl Transfer: ATP can donate a phosphoryl group to other
molecules in phosphorylation reactions, which is crucial for activating
substrates and enzymes.
3. ATP Hydrolysis: The hydrolysis of ATP to ADP (adenosine
diphosphate) and inorganic phosphate (Pi) releases a large amount of
free energy, which is used to drive endergonic reactions.

75. 7.3. Biological oxidation –reduction reactions
 Oxidation-reduction (redox) reactions are chemical reactions that
involve the transfer of electrons between molecules.
 These reactions are fundamental to energy transduction in cells.
 Key components include:
1. Oxidation: Loss of electrons from a molecule.
2. Reduction: Gain of electrons by a molecule.
3. Electron Carriers: Molecules like NAD+ (nicotinamide adenine
dinucleotide) and FAD (flavin adenine dinucleotide)
 that shuttle electrons during redox reactions.

76. Cont…
 Redox Potential: The tendency of a molecule to gain or lose
electrons.
 Molecules with a higher redox potential are more likely to
accept electrons.
What are Central Metabolic Pathways ?
These pathways are the major routes by which cells extract
energy from nutrients and produce essential biomolecules.
1. Glycolysis
2. Citric Acid Cycle (Krebs Cycle)
3. Oxidative Phosphorylation
4. Pentose Phosphate Pathway

77. Cont…
Energy Transduction
 Involves converting energy from one form to another within the cell.
 This is primarily achieved through the coupling of exergonic and
endergonic reactions.
Key processes include:
1. Chemiosmosis: The movement of ions (typically H+) across a
semipermeable membrane, down their electrochemical gradient.
 which drives ATP synthesis.
1. Proton Motive Force (PMF): The electrochemical gradient of protons
across the inner mitochondrial membrane.
 which is used to generate ATP through ATP synthase.

78. 7.4. Glycolysis, gluconeogenesis, and the
pentose phosphate pathway

79. 7.4.1. Glycolysis: an overview
Glycolysis is the first of cellular respiration’s.
 key metabolic routes to generate energy in the form of ATP.
 The six-carbon ring of glucose is broken into two three
carbon sugars of pyruvate.
 Two different phases through a series of enzyme reactions.
 The initial phase of glycolysis consumes energy,
 The second phase accomplishes the conversion to pyruvate and provides
ATP and NADH for usage by the cell.
 Overall, glycolysis provides two pyruvate molecules, two ATP molecules, and two
NADH molecules for energy.
 In the cytoplasm, the entire reaction of glycolysis.

80. Cont…
Overall, glycolysis provides two pyruvate molecules, two ATP
molecules, and two NADH molecules for energy.
C6H12O6 + 2NAD+
+ 2ADP + 2Pi → 2 pyruvic acid,
(CH3(C=O)COOH + 2ATP + 2NADH + 2H+
In the cytoplasm, the entire reaction of glycolysis.
 Glycolysis can take place with or without oxygen.
 In the absence of oxygen, glycolysis permits cells to produce
limited amounts of ATP by fermentation.
What are Importance of Glycolysis?
How Control of Glycolysis?

83. 7.4.2 The fate of pyruvate under anaerobic conditions
 The presence or absence of oxygen determines the fates of the
pyruvate produced in glycolysis.
 When plenty of oxygen is available (aerobic conditions),
pyruvate is first converted to acetyl-CoA.
 However, in the absence of oxygen (that is, under anaerobic
conditions),
 the fate of pyruvate is different in different organisms.
What is Fermentation and It’s types?

84. 7.4.3. Regulation of glycolysis
Enzymatic control can be exercised by three different common
methods.
A. Allosteric effectors.
 The transient binding of molecules to the enzyme to change the
conformation.
 Effect is observed in milliseconds.
B. Covalent modification.
 Generally phosphorylation.
 Effect in seconds.
C. Transcription of enzyme.
 Effect observed in hours

85. 7.4.4. Gluconeogenesis
Gluconeogenesis is a metabolic pathway that
results in the biosynthesis of glucose from
certain non-carbohydrate carbon substrates.
It primarily occurs in the liver.
 But it can also occur in minor levels in the small
intestine and kidney.
Gluconeogenesis and glycogenolysis serve the same
purpose.
 What are Importance of Gluconeogenesis?

87. 7.4.5. The pentose phosphate pathway
 The pentose phosphate pathway is a metabolic pathway parallel to glycolysis.
 Generates NADPH and pentose (5-carbon sugars) as well as ribose 5-
phosphate.
 It involves glucose oxidation.
 its primary role is anabolic rather than catabolic.
 It is an important pathway that generates precursors for nucleotide
synthesis.
 PPP occurs in the cytosol of liver cells, adrenal cortex, and lactating
mammary glands.
 In plants, most steps take place in plastids.

88. Cont…
Reactions of the Pentose Phosphate Pathway
• The PPP consists of two distinct phases: the oxidative and non-oxidative phases.
1.Oxidative Phase of Pentose Phosphate Pathway
2. Non-Oxidative Phase of Pentose Phosphate Pathway
The overall reaction of the pentose phosphate pathway
3 Glucose-6-P + 6 NADP+→ 3 ribulose-5-P + 3 CO2 + 6 NADPH
3 Ribulose-5-P → 2 xylulose-5-P + Ribose-5-P
2 Xylulose-5-P + Ribose-5-P → 2 fructose-6-P + Glyceraldehyde-3-P
 PPP Regulation.
 Feedback inhibition
 The enzymes glucose-6-phosphate dehydrogenase (G6PDH)
 6-phosphogluconate dehydrogenase (6PGDH) are particularly crucial in this control.
 Hormones(insulin and glucagon)

90. 7.5. Metabolic regulation
A. Hormonal Regulation
1. Insulin:
o Secreted by the pancreas in response to high blood glucose levels.
o Promotes glucose uptake by cells, particularly in muscle and adipose tissue.
o Stimulates glycogenesis (synthesis of glycogen) in the liver.
o Inhibits gluconeogenesis (glucose production from non-carbohydrates) in the liver.
2. Glucagon:
o Secreted by the pancreas in response to low blood glucose levels.
o Stimulates glycogenolysis (breakdown of glycogen) in the liver.
o Promotes gluconeogenesis in the liver.
o Inhibits glycolysis and stimulates gluconeogenesis.

91. Cont…
B. Enzyme Regulation
1. Hexokinase/Glucokinase:
o Hexokinase (in most tissues) has a low Km, allowing it to function efficiently at low
glucose concentrations.
o Glucokinase (in the liver) has a high Km and is active at high glucose concentrations.
It is regulated by glucokinase regulatory protein (GKRP) in response to glucose and
fructose-6-phosphate levels.
2. Phosphofructokinase-1 (PFK-1):
o A key regulatory enzyme in glycolysis.
o Activated by AMP, ADP, and fructose-2,6-bisphosphate (F2,6BP).
o Inhibited by ATP and citrate.
3. Pyruvate Kinase:
o Activated by fructose-1,6-bisphosphate (F1,6BP).
• Inhibited by ATP and alanine

92. Cont…
C. Allosteric Regulation
1. Glucose-6-Phosphate:
o Activates glycogen synthase, promoting glycogenesis.
o Inhibits glycogen phosphorylase, reducing
glycogenolysis.
2. AMP:
o Activates glycogen phosphorylase, promoting
glycogenolysis during low energy states (high AMP
levels).

93. 7.6. The citric acid cycle
 The Krebs cycle or TCA cycle (tricarboxylic acid cycle).
 Krebs cycle was named after Hans Krebs.
 is a series of enzyme catalysed reactions occurring in the
mitochondrial matrix under aerobic condition.
 It is the common pathway for complete oxidation of
carbohydrates, proteins and lipids.
 They are metabolised to acetyl coenzyme A or other
intermediates of the cycle.
 Glucose is fully oxidized in this process.
 Energy is stored in ATP and other high energy
compounds like 3NADH (each 3ATP) and 1FADH2(2ATP).
 So, total 12ATP produced in Krebs cycle

95. 7.6.1. Reactions of the citric acid cycle
Krebs cycle products
Each citric acid cycle forms the following products:
2 molecules of CO2 are released. Removal of CO2 or decarboxylation of citric acid takes
place at two places:
1. In the conversion of isocitrate (6C) to 𝝰-ketoglutarate (5C)
2. In the conversion of 𝝰-ketoglutarate (5C) to succinyl CoA (4C)
1 ATP is produced in the conversion of succinyl CoA to succinate
3 NAD+ are reduced to NADH and 1 FAD+ is converted to FADH2 in the following reactions:
3. Isocitrate to 𝝰-ketoglutarate → NADH
4. 𝝰-ketoglutarate to succinyl CoA → NADH
5. Succinate to fumarate → FADH2
4.Malate to Oxaloacetate → NADH

96. 7.6.2. Regulation of the citric acid cycle

97. 7.6.3. TCA intermediates as precursors for
biosynthesis

98. 7.6.4. The glyoxylate cycle
 In plants and in some bacteria, but not in animals.
 acetyl-CoA can serve as the starting material for the biosynthesis of
carbohydrates.
 A pathway that bypasses the two oxidative decarboxylations of the
citric acid cycle
 Animals can convert carbohydrates to fats.
 glyoxysomes, are the sites of the glyoxylate cycle.
 The fatty acids stored in the seeds are broken down for energy during
germi-nation.
 Two enzymes are responsible for produce glucose from fatty acids.
1. Isocitrate lyase cleaves isocitrate, producing glyoxylate and succinate.
2. Malate synthase catalyzes the reaction of glyoxylate with acetyl-CoA
to produce malate.

100. 7.7. Fatty Acid catabolism
 Catabolism of the fatty acyl-CoA occurs in the mitochondrial matrix.
 a sequence of four reactions known collectively as β-oxidation.
STEP 1: First oxidation of an alkane (dehydrogenation)
 A fatty acyl-CoA is oxidized to yield a trans double bond between the α-
and β- carbons (the second and third carbons).
 FAD is oxidizing agent and is converted to FADH2, which moves into the electron
transport chain.
STEP 2: Hydration
 (addition of water across the double bond ) The trans alkene is then
hydrated to form a secondary alcohol .
 The hydroxyl group is placed on the β-carbon.
STEP 3: Second oxidation (oxidation of an alcohol )
 The secondary alcohol is then oxidized to a ketone by NAD+
acting as
the oxidizing agent.
STEP 4: Cleavage
Acetyl-CoA cleaves off to yield a fatty acid that is two carbons shorter than before.

101. 7.7.1. Digestion, mobilization and transport of fats
Digestion
Fats are not soluble in water.
Made in bile salt that are
Absorbed as micelles in small intestines.
Chylomicron (Lipoproteins) carries
 protein that carry fats
Store in adipose tissue.
Role of Hormones
 Can mobilize from adipose tissue.
Release as fatty acids
 epinephrene and glucagon real ease cAMP.
Mobilize fats.

102. 7.7.2. Oxidation of fatty acids
A. Fatty Acid Activation
 Before fatty acids can be oxidized, they must be “primed” for reaction
in an ATP-dependent acylation reaction to form fatty acyl-CoA.
 The process is catalyzed by a family of three acyl-CoA
synthetases (also called thiokinases).
B. Transport Across the Mitochondrial Membrane
 A long-chain fatty acyl-CoA cannot directly cross the inner
mitochondrial membrane.
1. The acyl group of a cytosolic acyl-CoA is transferred to
carnitine, thereby releasing the CoA to its cytosolic pool.
2. The resulting acyl-carnitine is transported into the
mitochondrial matrix by the transport system.
3. The acyl group is transferred to a CoA molecule from the
mitochondrial pool.
4. The product carnitine is returned to the cytosol.

103. Cont…
C. Oxidation
 Fatty acids are dismembered through the oxidation of
fatty acyl-CoA.

104. The stages of fatty acid oxidation
These four stages keep repeating until
the whole molecule is oxidized
Stage 1: Dehydrogenation
Stage 2: Hydration
Stage 3: Oxidation
Stage 4: Thiolysis

105. Cont…
D. Oxidation of Unsaturated Fatty Acids
 Double bonds at these positions in fatty acids pose three
problems for the -oxidation pathway.
A. The first enzymatic difficulty occurs on the left-hand
pathway.
B. Double Bond Inhibits Hydratase Action.
C. The Unanticipated Isomerization of 2,5-Enoyl-CoA by 3,2-
Enoyl-CoA Isomerase
E. Oxidation of Odd-Chain Fatty Acids
 Some plants and marine organisms, however, synthesize fatty
acids with an odd number of carbon atoms.
 The final round of oxidation of these fatty acids forms propionyl-
CoA.
F. Peroxisomal Oxidation
 Peroxisomal oxidation in animals functions to shorten very long
chain fatty acids.

106. 7.7.3. Ketone bodies
 Ketone bodies are three water-soluble compounds.
 that are produced as by-products when fatty acids are broken down
for energy in the liver and kidney.
 a process known as ketogenesis
 The three ketone bodies are acetone, acetoacetic acid and beta-
hydroxybutyric acid.
 transported from the liver to other tissues.
 where acetoacetate and beta-hydroxybutyrate can be reconverted
to acetyl-CoA to produce energy, via the Krebs cycle.

107. Cont..
 serve as important metabolic fuels for many peripheral tissues,
particularly heart and skeletal muscle.
 during starvation, ketone bodies become the brain’s
major fuel source.
 Ketone bodies are water-soluble equivalents of fatty acids.

108. 7.8. Amino acid oxidation
is a metabolic process where amino acids are
broken down to produce energy.
 Synthesize new molecules, or generate metabolic
intermediates.
 This process is essential for maintaining nitrogen
balance and providing substrates for
 gluconeogenesis
 ketogenesis, and
the citric acid cycle

109. Cont…
Overview of Amino Acid Oxidation
1. Transamination
 The first step in amino acid oxidation involves the transfer
of the amino group from an amino acid to an α-keto acid.
 This reaction is catalyzed by aminotransferases
(transaminases).
 The common acceptor of the amino group is α-
ketoglutarate, which converts to glutamate.
 This process is important when dietary carbohydrates and fats are
insufficient

110. Cont…
2. Deamination
 The removal of the amino group from glutamate to form
ammonia (NH3) and α-ketoglutarate.
 This reaction is catalyzed by glutamate dehydrogenase.
 Ammonia is converted to urea in the liver via the urea cycle
and excreted by the kidneys.

111. Cont…
3. Oxidation of the Carbon Skeleton
 The remaining carbon skeleton (α-keto acid) is further oxidized to
produce energy or serve as intermediates in metabolic pathways.
 The carbon skeletons of amino acids can enter various pathways
depending on their structure:
o Glucogenic amino acids: These are converted into pyruvate or citric
acid cycle intermediates, which can be used for gluconeogenesis.
o Ketogenic amino acids: These are converted into acetyl-CoA or
acetoacetate, which can be used for ketogenesis or fatty acid synthesis.
 Both glucogenic and ketogenic: Some amino acids can produce
both glucose and ketone bodies

112. 7.8.1. Metabolic fates of amino acids
 Amino acids (AAs) are precursors for proteins.
 Precursors for many other biological N-containing
compounds.
 Energy metabolites: When degraded, amino acids
produce glucose, carbohydrates and ketone
bodies.
 Excess dietary AAs are neither stored nor
excreted.
Rather, they are converted to common metabolic
intermediates.

113. 7.8.2. Nitrogen excretion and the urea cycle
 Atmospheric nitrogen N2 is most abundant but is too inert for use in m
ost biochemical processes
Urea Cycle
 Ammonia generated from deamination is toxic and must be converted to
urea in the liver.
 The urea cycle includes the following key steps:
1. Formation of carbamoyl phosphate from ammonia and bicarbonate.
2. Synthesis of citrulline from carbamoyl phosphate and ornithine.
3. Conversion of citrulline to argininosuccinate with aspartate.
4. Formation of arginine from argininosuccinate, releasing fumarate.
 Hydrolysis of arginine to urea and ornithine

115. 7.8.3. Pathways of amino acid degradation
 Each of the 20 common amino acids has a unique structure.
 Their metabolic pathways differ.
 The first reaction in the breakdown of an amino acid is removal of
its -amino group(transamination reactions).
 Excreting excess nitrogen and degrading the remaining carbon
skeleton or converting it to glucose.
 is synthesized from ammonia and aspartate.
 Both of these are derived mainly from glutamate, a product of
most deamination reactions.

116. 7.9. Oxidative phosphorylation
The major steps of oxidative phosphorylation in
mitochondria
Delivery of Electrons by NADH and FADH2
Reduced NADH and FADH2 transfer their electrons
to molecules near the beginning of the transport chain.
After transferring the electrons, they get oxidized to
NAD+ and FAD and are utilized in other steps of
cellular respiration.

117. 7.9.1. The chemiosmotic theory and the mechanism of ATP synthesis

The chemi-osmotic theory deals with the generation of ATP by ATP
synthase.

Theory is about an electrochemical link between respiration and
phosphorylation.
It was proposed by Peter Mitchell in 1961.

The electrons move from a higher energy level to a lower energy level,
thereby releasing energy.

Some of the energy is used to move the electrons from the matrix to the
intermembrane space.
Thus, an electrochemical gradient is established.

ATP synthase Structure???????????????????

118. Cont…
ATP Synthesis
 The H+ ions pass through an enzyme called ATP synthase while flowing back into the
matrix.
 This controls the flow of protons to synthesize ATP.
Chemiosmosis involves the creation of a proton gradient through
the electron transport chain,
Driving ATP synthesis via ATP synthase.
 These 2 sets of reactions are coupled and interrelated.
 The electrons that flow through electron transport chain is an exergonic
process.
 the synthesis of ATP is an endergonic process.
What is the role of ATP Synthase in ATP Production?

119. Cont…
 Energy will be transmitted from the electron transport chain to ATP
synthase by the movement of proteins.
 This process is termed as chemiosmosis.
 Endergonic Process is a chemical reaction in which energy is
absorbed.
 There will be a change in free energy and it is always positive.
 Exergonic Process is a chemical reaction in which there will be a
positive flow of energy from the system to the surrounding
environment.
 Chemical reactions are also considered exergonic when they are
spontaneous.

121. 7.9.2. The electron transport system
 The electron transport chain (ETC) is a series of protein complexes.
 Consists of three protein complexes (complexes I, III, and IV),
 two mobile carrier molecules— ubiquinone (coenzyme Q) and
cytochrome -c.
 It consists of electrons having high transfer potential.
 These reactions release a huge amount of energy on oxidation.
 The electrons are separated from the NADH and then passed to the oxygen with a
series of enzymes releasing a small amount of energy.
 All these series of enzymes having complexes is known as electron transport chain.
 This can be considered as one of the best examples to understand the concept of oxidative
phosphorylation.

123. 7.9.3. Regulation of oxidative phosphorylation
The Regulation of the cycle is the
NADH/NAD+ Ratio.
In addition to pyruvate dehydrogenase (PDH)
and oxoglutarate dehydrogenase.
 citrate synthase and isocitrate
dehydrogenase are also inhibited by NAD+
deficiency or an excess of NADH+H+.
 Except of isocitrate dehydrogenase,these
subject to product inhibition by acetyl-
CoA, succinyl- CoA, or citrate.