Carbohydrate anabolism

A SEMINAR REPORT
ON
CARBOHYDRATE ANABOLISM
Submitted By: Submitted To:
Anshul kumar Dr. Monika Asthana
M.Sc. 1st
Semester Incharge
Biotechnology Dpt. Of Biotechnology
Submitted To:
School Of Life Sciences
Dr. Bhim Rao Ambedkar University Agra
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Carbohydrate
A carbohydrate is a biomolecule consisting of carbon(C), hydrogen(H)
and oxygen(O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1
(as in water) and thus with the empirical formula Cm(H2O)n (where m may
be different from n). This formula holds true for monosaccharides. Some
exceptions exist; for example, deoxyribose, a sugar component
of DNA, has the empirical formula C5H10O4.
The term is most common in biochemistry, where it is a synonym
of saccharide, a group that includes sugars, starch, and cellulose. The
saccharides are divided into four chemical groups:
monosaccharides, disaccharides, oligosaccharides, and polysaccharides.
Monosaccharides and disaccharides, the smallest (lower molecular weight)
carbohydrates, are commonly referred to as sugars. The word saccharide
comes from the Greek word (sákkharon), meaning "sugar". While the
scientific nomenclature of carbohydrates is complex, the names of the
monosaccharides and disaccharides very often end in the suffix -ose, as in
the monosaccharides fructose (fruit sugar) and glucose (starch sugar) and
the disaccharides sucrose (cane or beet sugar) and lactose (milk sugar).
Carbohydrates perform numerous roles in living organisms.
Polysaccharides serve for the storage of energy (e.g. starch and glycogen)
and as structural components (e.g. cellulose in plants and chitin in
arthropods). The 5-carbon monosaccharide ribose is an important
component of coenzymes (e.g. ATP, FAD and NAD) and the backbone of
the genetic molecule known as RNA. The related deoxyribose is a
component of DNA. Saccharides and their derivatives include many other
important biomolecules that play key roles in the immune
system, fertilization, preventing pathogenesis, blood clotting,
and development.

STRUCTURES OF SOME CARBOHYDRATES
Deoxyribose

Anabolism
Anabolism is the process by which the body utilizes the energy released by
catabolism to synthesize complex molecules. These complex molecules
are then utilized to form cellular structures that are formed from small and
simple precursors that act as building blocks.

Carbohydrate Anabolism
In this process simple organic acids can be converted into
monosaccharides such as glucose and then used to assemble
polysaccharides such as starch.

In the given chemical reaction the substrate pyruvate (pyruvic acid)
converted into a monosaccharide carbohydrate, glucose.
Stages of anabolism
There are three basic stages of anabolism.
 Stage 1- Involves production of precursors such as amino
acids, monosaccharides, isoprenoids and nucleotides.
 Stage 2- Involves activation of these precursors into reactive
forms using energy from ATP
 Stage 3- Involves the assembly of these precursors into
complex molecules such as proteins, polysaccharides,
lipids and nucleic acids.
Carbohydrate anabolism completed by many different types
of pathways such as gluconeogenesis in all organisms, Calvin cycle
in plants only and glyoxylate cycle which specifically occurs in micro-
organisms only.

Gluconeogenesis
Gluconeogenesis (GNG) is a anabolic pathway that results in the
generation of glucose from certain non-carbohydrate carbon substrates.
Gluconeogenesis is one of several main mechanisms
used by humans and many other animals to maintain blood glucose levels,
avoiding low levels (hypoglycemia). Other means include the degradation
of glycogen (glycogenolysis) and fatty acid catabolism.
Gluconeogenesis is a ubiquitous process, present in
plants, animals, fungi, bacteria, and other microorganisms. In vertebrates,
gluconeogenesis takes place mainly in the liver and, to a lesser extent, in
the cortex of the kidneys. In ruminants, this tends to be a continuous
process. In many other animals, the process occurs during periods
of fasting, starvation, low-carbohydrate diets, or intense exercise. The
process is highly endergonic until it is coupled to the hydrolysis
of ATP or GTP, effectively making the process exergonic. For example, the
pathway leading from pyruvate to glucose-6-phosphate requires 4
molecules of ATP and 2 molecules of GTP to proceed spontaneously.
Gluconeogenesis is often associated with ketosis. Gluconeogenesis is also
a target of therapy for type 2 diabetes, such as the antidiabetic
drug, metformin, which inhibits glucose formation and stimulates glucose
uptake by cells. In ruminants, because dietary carbohydrates tend to be
metabolized by rumen organisms, gluconeogenesis occurs regardless of
fasting, low-carbohydrate diets, exercise, etc.
Gluconeogenesis use pyruvate, lactate, propionate, Gluconic
amino acids and glycerol as a precursor for the production of carbohydrate
compounds.

Pyruvate as a precursor
After the glycolysis is completed and pyruvic acid is produced as a end
product. But glucose cannot be produced by reversing the glycolysis
process because there are three irreversible steps in glycolysis.
 1-Glucose to glucose-6-phosphate
 2-Fructose-6-phosphate to fructose-1,6-biphosphate
 3- 3-phosphoglycerate to 1,3-biphosphoglycerate
Gluconeogenesis from pyruvate share 7 reversible steps of glycolysis and
the 3 irreversible steps are bypassed by the separate sets of enzymes e.g;
pyruvate carboxylase, PEP carboxykinase, fructose-1,6-biphosphatase and
glucose-6-phosphatase respectively.
Conversion of pyruvate to phosphoenol-pyruvate:-
This conversion generally requires two exergonic reactions. Pyruvate is first
transported from the cytosol into mitochondria or is generated from alanine
within mitochondria by transamination, in which the a-amino group is
transferred from alanine (leaving pyruvate) to an a-keto carboxylic acid.
Then pyruvate carboxylase, a mitochondrial enzyme that requires the
coenzyme biotin, converts the pyruvate to oxaloacetate by
dephosphorylation of two ATP to ADP+Pi.
Because the mitochondrial membrane has no
transporter for oxaloacetate, before export to the cytosol the oxaloacetate
formed from pyruvate must be reduced to malate by mitochondrial malate
dehydrogenase, at the expense of NADH. Malate leaves the
mitochondrion through a specific transporter in the inner mitochondrial
membrane and in the cytosol it is reoxidized to oxaloacetate, with the
production of cytosolic NADH. The oxaloacetate is then converted to PEP
by phosphoenol pyruvate carboxykinase. This Mg2+
-dependent reaction
requires GTP as the phosphoryl group donor: The reaction is reversible
under intracellular conditions; the formation of one high-energy phosphate
compound (PEP) is balanced by the hydrolysis of another (GTP).

Conversion of fructose-1, 6-biphosphate to fructose-6-
phosphate:-
Fructose-1,6-biphosphate have two inorganic phosphate on their first and
last carbon atom respectively which undergoes the process de-
phosphorylation as a result one of the phosphate group is loosed by
compound with the help of enzyme fructose-1,6-biphosphatase(Mg2+
dependent) and results in the formation of fructose-6-phosphate.This
fructose-6-phosphate compound undergoes isomerisation and converted
into glucose-6-phosphate.
Conversion of glucose-6-phosphate into glucose:-
The third bypass is the final reaction of gluconeogenesis, the
dephosphorylation of glucose 6-phosphate to yield glucose. Reversal of the
Hexokinase reaction would require phosphoryl group transfer from glucose
6-phosphate to ADP, forming ATP, an energetically unfavorable reaction.
The reaction catalyzed by glucose 6-phosphatase does not require
synthesis of ATP; it is a simple hydrolysis of a phosphate ester This Mg21-
activated enzyme is found on the luminal side of the endoplasmic reticulum
of hepatocytes, renal cells, and epithelial cells of the small intestine, but not
in other tissues, which are therefore unable to supply glucose to the blood.
If other tissues had glucose 6-phosphatase, this enzyme’s activity would
hydrolyze the glucose 6-phosphate needed within those tissues for
glycolysis. Glucose produced by gluconeogenesis in the liver or kidney or
ingested in the diet is delivered to these other tissues, including brain and
muscle, through the bloodstream.

Pyruvate gluconeogenesis Is Energetically
Expensive:-
The sum of the biosynthetic reactions leading from pyruvate to free blood
glucose is:
2 Pyruvate + 14ATP + 12GTP + 12NADH + 2H+
+ 4H2O
Glucose + 4ADP + 2GDP + 6Pi + 2NAD+
For each molecule of glucose formed from pyruvate, six high-energy
phosphate groups are required, four from ATP and two from GTP. In
addition, two molecules of NADH are required for the reduction of two
molecules of 1,3-bisphosphoglycerate. Clearly, Equation is not simply the
reverse of the equation for conversion of glucose to pyruvate by glycolysis,
which would require only two molecules of ATP:
Glucose + 2ADP + 2Pi + NAD+
2 pyruvate + 2ATP + 2NADH + 2H+
+ 2H2O
The synthesis of glucose from pyruvate is a relatively expensive process.
Much of this high energy cost is necessary to ensure the irreversibility of
gluconeogenesis.

Lactate as a precursor
When the muscular of body perform an intense exercise, they use O2 very
faster than blood supplies to these tissues as a result they undergoes
anaerobic condition which shows decreasing in NAD/NADH ratio which
favours the fermentation reaction of pyruvate and produce lactate as a
product.
This lactic acid accumulated in muscles
results in muscles fatigue. Due to this condition these muscular tissues
need to extra energy so the lactate compound transported to liver tissues
where the gluconeogenesis process occurs and glucose in produced in
liver cells which used as an energy source.
 This cycle also known as Cori Cycle. Discovered by Carl Ferdinand
Cori and Gerty Cori.
 6ATP consumed during gluconeogenesis of two lactate molecules.

Glycerol as a precursor
Glycerol liberated in adipose tissues by the hydrolysis of fatty acid
triacylglyceride. But in adipose tissues enzyme glycerokinase in not
present it only present in liver and kidney which activate glycerol and
converted into glycerol-3-phosphate which is converted into
dihydroxyacetophosphate(DHAP) by enzyme glycerol-3-phosphate
hydrogenase. This DHAP molecule is an intermediate in glycolysis
which also undergoes gluconeogenesis and produce glucose with the
help of different types of specific catalytic enzymes.

Propionate as a precursor
Oxidation of odd chain fatty acid and the breakdown of some amino acids
(methionine and isoleucine) yields propionyl CoA with the action of enzyme
acyl CoA synthase which is a three carbon compound. When this 3
carbon compound produced Propionyl CoA carboxylase enzyme acts on
this in the presence of Mg2+
dependent ATP which converted into
AMP+PPi and biotin and converted to methyl melanoyl CoA in the presence
of enzyme propionyl CoA carboxylase following the dephosphorylation of
ATP now, this compound converted to succinyl CoA in the presence of
methyl melanoyl isomerase enzyme and B12. The latter is converted to
oxaloacetate and then malate in the Krebs cycle. Export of malate into the
cytosol leads to formation of oxaloacetate, phosphoenol pyruvate, and
other gluconeogenic intermediates as finally it produce glucose
monosaccharide which use as building block of many other biomolecules
and also as an energy source for body.

Regulation of gluconeogenesis
Gluconeogenesis process regulated by the means of enzymes, hormones
and also ATP.
1-Enzymatic regulation
 Pyruvate carboxylate:-Pyruvate to Oxaloacetate
 PEP carboxykinase:-Oxaloacetate to PEP
 Fructose-1,6-biphosphatase:-Fructose-1,6-biphpsphate to Fructose-
6-phosphate
 Glucose-6-phosphatase:-Glucose-6-phosphate to Glucose
 Glycerokinase:-Glycerol to Glycerol-3-phosphate
 Glycerol-3-phosphate dehydrogenase:-Glycerol-3-phosphate to
DHAP
 Acyl CoA synthase:-Propionate to Propionyl CoA
 Propionyl CoA carboxylase:-Propionyl CoA to Melanoyl CoA
 Methyl melanoyl isomerase:-Melanoyl CoA to succinyl CoA
2-Hormonal regulation
 Insulin:- Inhibit gluconeogenesis
 Glucocorticoids:- Promote gluconeogenesis
 Glucagon:- Promote gluconeogenesis
3-ATP
ATP acts as energy currency in gluconeogenesis because it is an
expensive process with respect to energy.

Significance of gluconeogenesis
 Brain, RBCs, Testes & Kidney medulla requires glucose for
continuous supply of energy.
 Human brain individually requires 120g of glucose out of 160g of
glucose requires by whole body per day.
 Glucose as a only source of energy to skeletal muscles.
 Gluconeogenesis maintains blood glucose level during fasting.

Calvin Cycle
The Calvin cycle, light-independent reactions, bio synthetic phase, dark
reactions, or photosynthetic carbon reduction (PCR)
cycle of photosynthesis is the chemical reactions that convert carbon
dioxide and other compounds into glucose. These reactions occur in
the stroma, the fluid-filled area of a chloroplast outside the thylakoid
membranes. These reactions take the products (ATP and NADPH) of light-
dependent reactions and perform further chemical processes on them.
There are three phases to the light-independent
reactions, collectively called the Calvin cycle:
1-Carbon fixation
2- Reduction reactions
3- Ribulose 1, 5-bisphosphate (RuBP) regeneration.
Though it is called the "dark reactions", the Calvin cycle does not actually
occur in the dark or during nighttime. This is because the process requires
reduced NADP which is short-lived and comes from the light-dependent
reactions. In the dark, plants instead release sucrose into the phloem from
their starch reserves to provide energy for the plant. The Calvin cycle thus
happens when light is available independent of the kind of photosynthesis
(C3 carbon fixation, C4 carbon fixation, and Crassulacean Acid Metabolism
(CAM); CAM plants store malic acid in their vacuoles every night and
release it by day to make this process work.

Energy consumed in Calvin cycle:-
 Net ATP consumed in one Calvin cycle= 9ATP
 Net NADPH consumed in one Calvin cycle=6NADP
 Total amount of energy consumed in One Calvin cycle=27ATP

Significance of Calvin cycle
 The product of Calvin cycle, glyceraldehyde-3-phosphate (G3P) can
be converted to many other molecules.
 e.g; Fatty acids
 Glycerol
 Amino acids
 Glyceraldehyde-3-phosphate converted to glucose-6-phosphate
which often metabolised for energy.

Glyoxylate Cycle
The glyoxylate cycle, a variation of the tricarboxylic acid cycle, is
an anabolic pathway occurring in plants, bacteria, protists, and fungi. The
glyoxylate cycle centers on the conversion of acetyl-CoA to succinate for
the synthesis of carbohydrates. In microorganisms, the glyoxylate cycle
allows cells to utilize simple carbon compounds as a carbon source when
complex sources such as glucose are not available. The cycle is generally
assumed to be absent in animals, with the exception of nematodes at the
early stages of embryogenesis. In recent years, however, the detection
of malate synthase (MS) and isocitrate lyase (ICL), key enzymes involved
in the glyoxylate cycle, in some animal tissue has raised questions
regarding the evolutionary relationship of enzymes
in bacteria and animals and suggests that animals encode alternative
enzymes of the cycle that differ in function from known MS and ICL in non-
metazoan species.
Plants as well as some algae and bacteria can use acetate as the carbon
source for the production of carbon compounds. Plants and bacteria
employee a modification of the TCA cycle called the glyoxylate cycle to
produce four carbon dicarboxylic acid from two carbon acetate units. The
glyoxylate cycle bypasses the two oxidative decarboxylation of the TCA
cycle and directly convert isocitrate through isocitrate lyase and malate
synthase into malate and succinate.

Significance of glyoxylate cycle
 It occurs in bacteria when the cultured in acetate rich carbon source.
 When higher fatty acids are oxydised into acetyl CoA without forming
pyruvic acids, then acetyl CoA enters into glyoxylate cycle.

Acknowledgement
Primarily I would thank God for being able to complete this
report with success. Then I would like to thank my teachers
namely Dr. Monika Asthana mam, Dr. Avnish Kumar sir, Dr.
Ankur Gupta sir and Dr. Bhavyata Dua mam whose valuable
guidance has been the ones that helped me patch this report
and make it full proof success his suggestions and his
instructions has served as the major contributor towards the
completion of the project.
Then I would like to thank my seniors namely Mr. Dheeraj sir
and Mr. Prashant Sharma who have helped me with their
valuable suggestions and guidance has been helpful in various
phases of the completion of this report.
Anshul Kumar

References
 Nelson D.L. & Cox M.M.(2013). Lehninger principles of biochemistry.
Sixth edition. New York. Susan Winslow

Contents
1. Carbohydrate
2. Structure of some carbohydrates
3. Anabolism
4. Carbohydrate anabolism
5. Stages of anabolism
6. Gluconeogenesis
 Pyruvate as a precursor
 Pyruvate gluconeogenesis is an energetically expensive
 Lactate as precursor
 Glycerol as a precursors
 Propionate as a precursors
 Regulation of gluconeogenesis
 Significance of gluconeogenesis
7. Calvin Cycle
 Energy consumed in Calvin Cycle
 Significance of Calvin Cycle
8. Glyoxylate Cycle
 Significance of glyoxylate cycle

Carbohydrate anabolism

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