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Submitted By :
Deepak J. Askar
M. Pharm 1 st sem
Roll No. 20073
Submitted To :
Prof. Jai Malik
• Carbohydrate metabolism is the whole of the biochemical processes responsible for
the metabolic formation, breakdown, and interconversion
of carbohydrates in living organisms.
- Carbohydrates are central to many essential metabolic pathways. Plants synthesize
carbohydrates from carbon dioxide and water through photosynthesis, allowing them
to store energy absorbed from the sunlight internally.
- Although humans consume a variety of carbohydrates, digestion breaks down
complex carbohydrates into a few simple monomers (monosaccharides) for
metabolism: glucose, fructose, and galactose. Glucose constitutes about 80% of the
products and is the primary structure that is distributed to cells in the tissues, where it
is broken down or stored as glycogen.
- The aerobic respiration, is the main form of cellular respiration used by humans,
glucose and oxygen are metabolized to release energy, with carbon
dioxide and water as by-products.
 MAJOR METABOLIC PATHWAYS OF CARBOHYDRATES METABOLISM
:
1.GLYCOLYSIS
2.CORI’S CYCLE
3.KREB CYCLE
4.GLUCONEOGENESIS
5.GLYCOGENESIS
6.GLYCOGENOLYSIS
7.Cahill Cycle
 MINOR METABOLIC PATHWAYS OF CARBOHYDRATES
METABOLISMS :
1.HMP SHUNT
2.URONIC ACID PATHWAYS
3.FRUCTOSE METABOLISM
4.GALACTOSE METABOLISM
Glycolysis (from the Greek Glykos, meaning sweet, and lysis,
meaning splitting) involves the breakdown of glucose, a simple
sugar, This process can occur in the presence or absence of
oxygen, that is, under aerobic or anaerobic conditions.
During the 1930s, the efforts of several German biochemists, including
Gustav Embden, Otto Meyerhof, and Jacob Parnas, determined that
glycolysis involves 10 steps, each one catalyzed by a different enzyme.
 Glycolysis: (EMP Pathway)
Step 1
ATP ADP
Glucose
Glucose is phosphorylated by ATP. Glucose-6-phosphate
is more easily trapped in the cell compared to glucose.
Glucose-6-Phosphate
Hexokinase
Step 2
The structure of glucose-6-phosphate is rearrangedto
fructose-6-phosphate.
Glucose-6-Phosphate
Phosphogluco
isomerase
Fructose-6-phosphate
Step 3
ATP ADP
Fructose-6-phosphate is phosphorylated
to make fructose-1,6-bisphosphate.
Phosphofructo
kinase
Fructose-6-phosphate
Fructose-1,6-bisphosphate
Fructose-1,6-bisphosphate
Dihydroxyacetone
phosphate
Glyceraldehyde-3-
phosphate (x2)
dihydroxyacetone phosphate and
glyceraldehyde-3-phosphate.
4. Fructose-1,6-bisphosphate is cleavedinto
Aldolase
4.
Isomerized to glyceraldehyde-3-phosphate.
5. Di-hydroxyl-acetone phosphateis
Isomerase
5.
Glyceraldehyde-3-
phosphate (x2)
1,3-bisphosphoglycerate (x2)
2 NAD+
Glyceraldehyde-3-
phosphate
dehydrogenase
2NADH
+2H+
Glyceraldehyde-3-phosphate is oxidized to 1,3-
bisphosphoglycerate. NADH is produced. In 1,3-bis-
phospho-glycerate,the phosphate group in theupper left
is destabilized, meaning that the bond will break in a
highly exergonicreaction.
Unstable Phosphate
Bond
6.
1,3-bisphosphoglycerate (x2)
Unstable Phosphate
Bond
2ATP 2ADP
Phosphoglycero–
kinase
7. A phosphate is removed from 1,3-bis-phospho-glycerate
to form 3-phosphor-glycerate. The removed phosphate is
transferred to ADP to make ATP via substrate-level
phosphorylation.
3-phosphoglycerate(x2)
3-phosphoglycerate(x2) 2-phosphoglycerate(x2)
Phosphoglycero–
mutase
8. The phosphate group in3 phosphoglycerate
is moved to a new location, creating 2-
phosphoglycerate
2-phosphoglycerate(x2)
Unstable phosphate
bond
Phosphoenolpyruvate(x2)
9. A water molecule is removed from 2-phosphor-glycerate to
form phosphor-enol-pyruvate. In phosphor-enol-pyruvate,
the phosphate group is destabilized, meaning that the bond
will break in a highly exergonic reaction.
Enolase
Unstable phosphate
bond
Phosphoenolpyruvate(x2) pyruvate(x2)
Pyruvate Kinase
2ADP 2ATP
10. A phosphate is removed from phosphor-enol-pyruvate
to form pyruvate. The removed phosphate is transferred
to ADP to make ATP via substrate-level phosphorylation.
Intermediate step between Glycolysis and Kreb’s Cycle:-
 KREB CYCLE
• Hans Adolf Krebs Biochemist; born in Germany. Worked in Britain. His
discoveryin 1937of the ‘Krebs cycle’ of chemical reactions was
critical to the understanding of cell metabolism
• And earned him the 1953 Nobel Prize for Physiology
or Medicine.
Phasesof Kreb Cycle
Step1-
• The Acetic acid subunit of Acetyl co – A combined with oxaloacetate to form a molecule of
citrate . The acetyl coenzyme A acts only as a transporter of acetic acid from
one enzyme to another.
Step 2 -
The citric acid molecule undergoes an isomerization. A hydroxyl group and a hydrogen molecule are
removed from the citrate structure in the form of water. The two carbons form a double bond until
the water molecule is added back. Thus, isocitrate is formed.
Step 3 -
•In this step, the isocitrate molecule is oxidized by a NAD molecule. The NAD molecule is reduced by
the hydrogen atom and the hydroxyl group. The NAD binds with a hydrogen atom and carries off the
other hydrogen atom leaving a carbonyl group. This structure is very unstable, so a molecule of CO2 is
released creating alpha-ketoglutarate
Step 4 -
• In this step, our friend, coenzymeA, returns to oxidize thealpha-ketoglutaratemolecule.
Amoleculeof NADis reducedagain to form NADHandleaveswith another hydrogen.
Thisinstabilitycausesacarbonylgroupto be releasedascarbondioxide andathioester
bond is formed in its placebetween the former alpha- ketoglutarateandcoenzymeAto
createamolecule of succinyl-coenzyme A complex.
Step 5 -
• A water molecule sheds its hydrogen atoms to coenzyme A. Then, a free-
floating phosphate group displaces coenzyme A and forms a bond with
the succinyl complex. The phosphate is
then transferred to a molecule of GDP to produce an energy molecule of
GTP. I t leaves behind amolecule of succinate .
Step 6 -
• In this step, succinate is oxidized by a molecule of FAD ( Flavin
adenine
• dinucleotide).The FAD removes two hydrogen atoms from the succinate and
forces a double bond to form between the two carbon atoms,
• thus creating fumarate .
Step 7 –
• An enzyme adds water to the fumarate molecule to form malate. The malate is
created by adding one hydrogen atom to a carbon atom and then
adding a hydroxyl group to acarbon next to a terminal carbonyl group.
Step 8 -
• In this final step, the malate molecule is oxidized by a NAD molecule. The carbon
that carried the hydroxyl group is now converted into a carbonyl group. The end
product is oxaloacetate which can then combine with acetyl- coenzyme A and
begin the Krebs cycle all over again.
 Energetics of Glycolysis And TCA Cycle:
 TotalEnergy/GlucoseInAerobicRespiration:-
• 3 molecules of ATP from each NADH and H+ produced (10 NADH + H+) x 3 ATP molecules
= 30 ATP molecules)
2 molecules of ATP from each FADH
• (2 FADH x 2ATP molecule= 4 ATP molecules)
• total: 34 ATP molecules
 CORI’S CYCLE (LACTIC ACID CYCLE)
• Lactate form by Glycolysis process in skeletal muscles and
Erythrocytes, is transported into the liver and kidney where It
Reforms into the Glucose, which again Becomes available via
circulation for oxidation in the tissues.
- USES :-
1. Prevents Lactate accumulation in the muscle.
2. Reutilize lactate from Muscle and Erythrocyte for
Gluconeogenesis.
 Cahill Cycle : (Glucose-Alanine Cycle)
• Uses of Glucose Alanine Cycle:-
• 1. Carries amino group to the liver.
• 2. Alanine use as a substrate for Gluconeogenesis During Starvation.
• 3. Amino acid is increased in blood During Starvation is Alanine.
 Gluconeogenesis:-
The Process of Formation of Glucose or Glycogen From Non- Carbohydrate Precursors is called as Gluconeogenesis.
 Pathway :
• CONVERSION OF PYRUVATE TO PHOSPHOENOL PYRUVATE (PEPA) - Pyruvate is transported from cytosol to
mitochondria or generated from alanine by transamination within mitochondria. Then, pyruvate carboxylase, an
enzyme that uses biotin as a coenzyme; converts pyruvate to oxaloacetate.
PYRUVATE + HCO₃⁻ + ATP OXALOACETATE + ADP + Pi
Because mitochondrial membrane has no transporter for oxaloacetate, so pyruvate is reduced to malate by malate
dehydrogenase at the expense of NADH.
OXALOACETATE + NADH + H⁺ ↔ L-MALATE + NAD⁺
Malate leaves the mitochondrion through a specific transporter in the inner mitochondrial membrane and in cytosol, it
is re-oxidised to oxaloacetate, with the production of cytosolic NADH.
MALATE + NAD⁺ OXALOACETATE + NADH + H⁺
The oxaloacetate is then converted to PEP by phosphoenolpyruvate carboxy-kinase.
OXALOACETATE + GTP ↔ PEPA + CO₂ + GDP
Glycogenesis:-
• Glycogen is the major storage form of carbohydrate in animals similar to starch in
plants.
• It is a homopolymer made up of repeated units of α- D glucose and each molecule is
linked to another by 1→4 glycosidic bond which is a link connecting the 1st C atom of
the active glucose residue to the 6th C atom of the approaching glucose molecule.
• Once there is a chain consisting of 8 to 10 glycosidic residues in the glycogen fragment,
branching begins by 1→6 linkages.
• Glycogenesis is the process of glycogen synthesis, in which glucose molecules are
added to chains of glycogen for storage.
• Steps involve in Glycogenesis:-
1.Glucose phosphorylation – In the initial phase, glucose is phosphorylated into glucose-6-
phosphate, a usual reaction in glycolysis. It is catalyzed by glucokinase (liver) and hexokinase
(muscle).
2.Conversion of Glu-6-P to Glu-1-P – An enzyme Phosphoglucomutase will catalyze the
conversion of Glucose-6-P is converted to Glu-1-Phosphate.
3.UTP (uridine triphosphate) attaches to Glu-1-P – The third step focuses on the reaction of
glucose-1-P to UTP thereby forming active nucleotide UDP-Glu (Uridine diphosphate glucose).
The one responsible for such reaction is the enzyme UDP-Glu-Pyro phosphorylase.
4.UDP-Glu attaches to glycogen primer – A small fragment of already existing glycogen will
serve as a primer in order to stimulate the synthesis of glycogen. The glucose from UDP-Glu will
be accepted by glycogenin. The initial glucose unit is attached to the hydroxyl group of tyrosine
of glyogenin. The first molecule of glucose is transferred to glycogenin, which will then takes up
for glucose residues forming a fragment of primer. It will be the one to accept all glucose
molecules.
5.Glycogen synthase synthesizes glycogen – Glycogen synthase transfers glucose from UDP-
Glu to glycogen (non-reducing end) forming alpha 1,4-linkages. The same enzyme catalyzes
the synthesis of the unbranched molecule with alpha-1,4-glycosidic linkages.
6.The formation of glycogen branches – The final step is the formation of glycogen branches
caused by the effect of branching enzyme, which transfers a small fragment of about five to
eight residues of glucose from the non-reducing end of the glycogen chain to another glucose
residue linked by alpha-1,6 bond. This action causes the formation of a new non-reducing end.
The final result is the elongation and branching out of the glycogen chain.
 Glycogenolysis :-
1.Glycogenolysis is a metabolic process by which
glycogen, the primary carbohydrate stored in the liver and
muscle cells of animals, is broken down into glucose to
provide immediate energy and to maintain blood glucose
levels during fasting.
2.Glycogen is catabolized by removal of a glucose
monomer through cleavage with inorganic phosphate to
produce glucose-1-phosphate.
This derivative of glucose is then converted to glucose-6-
phosphate, an intermediate in glycolysis.
3.It takes place in the muscle and liver tissues, where
glycogen is stored, as a hormonal response to epinephrine
and/or glucagon.
This Enzyme
Expressed only in
Liver, Kidney and
Intestine.
• Steps Involve in Glycogenolysis :
• 1. Breaking of Alpha- 1,4 Linkages:
• Glycogen Phosphorylase Cleave the alpha 1,4 Linkage.
• Release Glucose 1 Phosphate Not Free Glucose.
• Glycogen Phosphorylase Stop its action when it is at least 4 glucose residue
remain on Branch chain.
• 2. Removal Of Branches :
• 1. First Part is a Alpha- 1,4 alpha 1,4 Glucan Transferase :
• - Transfer trisaccharide residue to another forming a new alpha 1,4 linkage.
• 2. Second part is alpha- 1,6 Glucosidase ( Amylo - 1,6 Glucosidase )
• Hydrolyses The Branching point.
• Release Free Glucose Not Glucose 1 phosphate.
• 3. Conversion of Glucose 1 phosphate to Free Glucose :
• Glucose 1 phosphate converted into Glucose 6 Phosphate by Phosphoglucomutase.
• Glucose 6 phosphate convert into Glucose By Glucose 6 phosphatase (Liver, Kidney)
 Minor Pathways Of Carbohydrate Metabolism :
1. HMP Shunt / Pentose Phosphate pathway :
• Pentose phosphate pathway is also called Hexose monophosphate
pathway/ HMP shunt/ Phospho-gluconate pathway.
• It is an alternative route for the metabolism of glucose.
• It is more complex pathway than glycolysis. It is more anabolic in
nature.
• It takes place in cytosol. The tissues such as liver, adipose tissue,
adrenal gland, erythrocytes, testes and lactating mammary gland are
highly active in HMP shunt.
• It concern with the biosynthesis of NADPH and pentoses.
• Importance of Pentoses :-
1) The pentose and its derivatives are used for the synthesis of nucleic
acids(DNA, RNA) & many nucleotides(ATP, NAD+, CoA).
2) When an organism growing on pentose sugar(5c), this pathway is
used to produce carbohydrates for cell wall synthesis.
2. Uronic acid Pathway :-
1. An alternative oxidative Pathway for Glucose.
2. UDP Glucose converted to UDP Glucuronic
acid (Glucuronate) by Using NAD.
3. No ATP is Formed.
4. Site – Liver
5. Organelles – Cytosol
3. Fructose Metabolism :
•Fructose is an abundant sugar in the
human diet.
•This dietary monosaccharide is present
naturally in fruits and vegetables, either as
free fructose or as part of
the disaccharide sucrose, and as its
polymer inulin.
•Sucrose (table sugar) is a disaccharide
which when hydrolyzed yields fructose and
glucose.
•The metabolism of fructose from dietary
sources is referred to as fructolysis.
4. Galactose Metabolism :
• Galactose (galacto- + -ose, "milk sugar") sometimes abbreviated Gal,
is a monosaccharide sugar that is about as sweet as glucose, and
about 65% as sweet as sucrose. It is an aldohexose and a
C4 epimer of glucose. A galactose molecule linked with
a glucose molecule to form a lactose molecule.
• Galactan is a polymeric form of galactose found in hemicellulose, and
forming the core of the galactans, a class of natural polymeric
carbohydrates.
• References :
1. Carbohydrates and Glycobiology by Lehninger’s principles of Biochemistry by David L. Nelson
and Michael M. Cox, Chapter 7 pg. no. 239-267 .
2. www.wikipedia.org
3. Book of Biochemistry by U. Satyanarayana, and U. Chakrapani 3rd Edition, Section 3 pg.no. 244-
284.
4. Illustrated Biochemistry – Harper’s 26 th edition Pg. no. 130- 163.
5. Self assessment and Review of Biochemistry By Rebecca James, 4 th Edition 2018, Forewords by
Gobind Garg, Devesh Mishra, Apurv Mehra pg. no. 142 - 186
Metabolism of Carbohydrates

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Metabolism of Carbohydrates

  • 1. Submitted By : Deepak J. Askar M. Pharm 1 st sem Roll No. 20073 Submitted To : Prof. Jai Malik
  • 2. • Carbohydrate metabolism is the whole of the biochemical processes responsible for the metabolic formation, breakdown, and interconversion of carbohydrates in living organisms. - Carbohydrates are central to many essential metabolic pathways. Plants synthesize carbohydrates from carbon dioxide and water through photosynthesis, allowing them to store energy absorbed from the sunlight internally. - Although humans consume a variety of carbohydrates, digestion breaks down complex carbohydrates into a few simple monomers (monosaccharides) for metabolism: glucose, fructose, and galactose. Glucose constitutes about 80% of the products and is the primary structure that is distributed to cells in the tissues, where it is broken down or stored as glycogen. - The aerobic respiration, is the main form of cellular respiration used by humans, glucose and oxygen are metabolized to release energy, with carbon dioxide and water as by-products.
  • 3.  MAJOR METABOLIC PATHWAYS OF CARBOHYDRATES METABOLISM : 1.GLYCOLYSIS 2.CORI’S CYCLE 3.KREB CYCLE 4.GLUCONEOGENESIS 5.GLYCOGENESIS 6.GLYCOGENOLYSIS 7.Cahill Cycle
  • 4.  MINOR METABOLIC PATHWAYS OF CARBOHYDRATES METABOLISMS : 1.HMP SHUNT 2.URONIC ACID PATHWAYS 3.FRUCTOSE METABOLISM 4.GALACTOSE METABOLISM
  • 5. Glycolysis (from the Greek Glykos, meaning sweet, and lysis, meaning splitting) involves the breakdown of glucose, a simple sugar, This process can occur in the presence or absence of oxygen, that is, under aerobic or anaerobic conditions. During the 1930s, the efforts of several German biochemists, including Gustav Embden, Otto Meyerhof, and Jacob Parnas, determined that glycolysis involves 10 steps, each one catalyzed by a different enzyme.  Glycolysis: (EMP Pathway)
  • 6.
  • 7. Step 1 ATP ADP Glucose Glucose is phosphorylated by ATP. Glucose-6-phosphate is more easily trapped in the cell compared to glucose. Glucose-6-Phosphate Hexokinase
  • 8. Step 2 The structure of glucose-6-phosphate is rearrangedto fructose-6-phosphate. Glucose-6-Phosphate Phosphogluco isomerase Fructose-6-phosphate
  • 9. Step 3 ATP ADP Fructose-6-phosphate is phosphorylated to make fructose-1,6-bisphosphate. Phosphofructo kinase Fructose-6-phosphate Fructose-1,6-bisphosphate
  • 10. Fructose-1,6-bisphosphate Dihydroxyacetone phosphate Glyceraldehyde-3- phosphate (x2) dihydroxyacetone phosphate and glyceraldehyde-3-phosphate. 4. Fructose-1,6-bisphosphate is cleavedinto Aldolase 4. Isomerized to glyceraldehyde-3-phosphate. 5. Di-hydroxyl-acetone phosphateis Isomerase 5.
  • 11. Glyceraldehyde-3- phosphate (x2) 1,3-bisphosphoglycerate (x2) 2 NAD+ Glyceraldehyde-3- phosphate dehydrogenase 2NADH +2H+ Glyceraldehyde-3-phosphate is oxidized to 1,3- bisphosphoglycerate. NADH is produced. In 1,3-bis- phospho-glycerate,the phosphate group in theupper left is destabilized, meaning that the bond will break in a highly exergonicreaction. Unstable Phosphate Bond 6.
  • 12. 1,3-bisphosphoglycerate (x2) Unstable Phosphate Bond 2ATP 2ADP Phosphoglycero– kinase 7. A phosphate is removed from 1,3-bis-phospho-glycerate to form 3-phosphor-glycerate. The removed phosphate is transferred to ADP to make ATP via substrate-level phosphorylation. 3-phosphoglycerate(x2)
  • 13. 3-phosphoglycerate(x2) 2-phosphoglycerate(x2) Phosphoglycero– mutase 8. The phosphate group in3 phosphoglycerate is moved to a new location, creating 2- phosphoglycerate
  • 14. 2-phosphoglycerate(x2) Unstable phosphate bond Phosphoenolpyruvate(x2) 9. A water molecule is removed from 2-phosphor-glycerate to form phosphor-enol-pyruvate. In phosphor-enol-pyruvate, the phosphate group is destabilized, meaning that the bond will break in a highly exergonic reaction. Enolase
  • 15. Unstable phosphate bond Phosphoenolpyruvate(x2) pyruvate(x2) Pyruvate Kinase 2ADP 2ATP 10. A phosphate is removed from phosphor-enol-pyruvate to form pyruvate. The removed phosphate is transferred to ADP to make ATP via substrate-level phosphorylation.
  • 16. Intermediate step between Glycolysis and Kreb’s Cycle:-
  • 17.  KREB CYCLE • Hans Adolf Krebs Biochemist; born in Germany. Worked in Britain. His discoveryin 1937of the ‘Krebs cycle’ of chemical reactions was critical to the understanding of cell metabolism • And earned him the 1953 Nobel Prize for Physiology or Medicine.
  • 18.
  • 20. Step1- • The Acetic acid subunit of Acetyl co – A combined with oxaloacetate to form a molecule of citrate . The acetyl coenzyme A acts only as a transporter of acetic acid from one enzyme to another. Step 2 - The citric acid molecule undergoes an isomerization. A hydroxyl group and a hydrogen molecule are removed from the citrate structure in the form of water. The two carbons form a double bond until the water molecule is added back. Thus, isocitrate is formed. Step 3 - •In this step, the isocitrate molecule is oxidized by a NAD molecule. The NAD molecule is reduced by the hydrogen atom and the hydroxyl group. The NAD binds with a hydrogen atom and carries off the other hydrogen atom leaving a carbonyl group. This structure is very unstable, so a molecule of CO2 is released creating alpha-ketoglutarate
  • 21. Step 4 - • In this step, our friend, coenzymeA, returns to oxidize thealpha-ketoglutaratemolecule. Amoleculeof NADis reducedagain to form NADHandleaveswith another hydrogen. Thisinstabilitycausesacarbonylgroupto be releasedascarbondioxide andathioester bond is formed in its placebetween the former alpha- ketoglutarateandcoenzymeAto createamolecule of succinyl-coenzyme A complex. Step 5 - • A water molecule sheds its hydrogen atoms to coenzyme A. Then, a free- floating phosphate group displaces coenzyme A and forms a bond with the succinyl complex. The phosphate is then transferred to a molecule of GDP to produce an energy molecule of GTP. I t leaves behind amolecule of succinate .
  • 22. Step 6 - • In this step, succinate is oxidized by a molecule of FAD ( Flavin adenine • dinucleotide).The FAD removes two hydrogen atoms from the succinate and forces a double bond to form between the two carbon atoms, • thus creating fumarate . Step 7 – • An enzyme adds water to the fumarate molecule to form malate. The malate is created by adding one hydrogen atom to a carbon atom and then adding a hydroxyl group to acarbon next to a terminal carbonyl group. Step 8 - • In this final step, the malate molecule is oxidized by a NAD molecule. The carbon that carried the hydroxyl group is now converted into a carbonyl group. The end product is oxaloacetate which can then combine with acetyl- coenzyme A and begin the Krebs cycle all over again.
  • 23.  Energetics of Glycolysis And TCA Cycle:
  • 24.  TotalEnergy/GlucoseInAerobicRespiration:- • 3 molecules of ATP from each NADH and H+ produced (10 NADH + H+) x 3 ATP molecules = 30 ATP molecules) 2 molecules of ATP from each FADH • (2 FADH x 2ATP molecule= 4 ATP molecules) • total: 34 ATP molecules
  • 25.  CORI’S CYCLE (LACTIC ACID CYCLE) • Lactate form by Glycolysis process in skeletal muscles and Erythrocytes, is transported into the liver and kidney where It Reforms into the Glucose, which again Becomes available via circulation for oxidation in the tissues. - USES :- 1. Prevents Lactate accumulation in the muscle. 2. Reutilize lactate from Muscle and Erythrocyte for Gluconeogenesis.
  • 26.  Cahill Cycle : (Glucose-Alanine Cycle)
  • 27. • Uses of Glucose Alanine Cycle:- • 1. Carries amino group to the liver. • 2. Alanine use as a substrate for Gluconeogenesis During Starvation. • 3. Amino acid is increased in blood During Starvation is Alanine.
  • 28.  Gluconeogenesis:- The Process of Formation of Glucose or Glycogen From Non- Carbohydrate Precursors is called as Gluconeogenesis.  Pathway : • CONVERSION OF PYRUVATE TO PHOSPHOENOL PYRUVATE (PEPA) - Pyruvate is transported from cytosol to mitochondria or generated from alanine by transamination within mitochondria. Then, pyruvate carboxylase, an enzyme that uses biotin as a coenzyme; converts pyruvate to oxaloacetate. PYRUVATE + HCO₃⁻ + ATP OXALOACETATE + ADP + Pi Because mitochondrial membrane has no transporter for oxaloacetate, so pyruvate is reduced to malate by malate dehydrogenase at the expense of NADH. OXALOACETATE + NADH + H⁺ ↔ L-MALATE + NAD⁺ Malate leaves the mitochondrion through a specific transporter in the inner mitochondrial membrane and in cytosol, it is re-oxidised to oxaloacetate, with the production of cytosolic NADH. MALATE + NAD⁺ OXALOACETATE + NADH + H⁺ The oxaloacetate is then converted to PEP by phosphoenolpyruvate carboxy-kinase. OXALOACETATE + GTP ↔ PEPA + CO₂ + GDP
  • 29.
  • 30. Glycogenesis:- • Glycogen is the major storage form of carbohydrate in animals similar to starch in plants. • It is a homopolymer made up of repeated units of α- D glucose and each molecule is linked to another by 1→4 glycosidic bond which is a link connecting the 1st C atom of the active glucose residue to the 6th C atom of the approaching glucose molecule. • Once there is a chain consisting of 8 to 10 glycosidic residues in the glycogen fragment, branching begins by 1→6 linkages. • Glycogenesis is the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage.
  • 31.
  • 32. • Steps involve in Glycogenesis:- 1.Glucose phosphorylation – In the initial phase, glucose is phosphorylated into glucose-6- phosphate, a usual reaction in glycolysis. It is catalyzed by glucokinase (liver) and hexokinase (muscle). 2.Conversion of Glu-6-P to Glu-1-P – An enzyme Phosphoglucomutase will catalyze the conversion of Glucose-6-P is converted to Glu-1-Phosphate. 3.UTP (uridine triphosphate) attaches to Glu-1-P – The third step focuses on the reaction of glucose-1-P to UTP thereby forming active nucleotide UDP-Glu (Uridine diphosphate glucose). The one responsible for such reaction is the enzyme UDP-Glu-Pyro phosphorylase. 4.UDP-Glu attaches to glycogen primer – A small fragment of already existing glycogen will serve as a primer in order to stimulate the synthesis of glycogen. The glucose from UDP-Glu will be accepted by glycogenin. The initial glucose unit is attached to the hydroxyl group of tyrosine of glyogenin. The first molecule of glucose is transferred to glycogenin, which will then takes up for glucose residues forming a fragment of primer. It will be the one to accept all glucose molecules. 5.Glycogen synthase synthesizes glycogen – Glycogen synthase transfers glucose from UDP- Glu to glycogen (non-reducing end) forming alpha 1,4-linkages. The same enzyme catalyzes the synthesis of the unbranched molecule with alpha-1,4-glycosidic linkages. 6.The formation of glycogen branches – The final step is the formation of glycogen branches caused by the effect of branching enzyme, which transfers a small fragment of about five to eight residues of glucose from the non-reducing end of the glycogen chain to another glucose residue linked by alpha-1,6 bond. This action causes the formation of a new non-reducing end. The final result is the elongation and branching out of the glycogen chain.
  • 33.  Glycogenolysis :- 1.Glycogenolysis is a metabolic process by which glycogen, the primary carbohydrate stored in the liver and muscle cells of animals, is broken down into glucose to provide immediate energy and to maintain blood glucose levels during fasting. 2.Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate. This derivative of glucose is then converted to glucose-6- phosphate, an intermediate in glycolysis. 3.It takes place in the muscle and liver tissues, where glycogen is stored, as a hormonal response to epinephrine and/or glucagon.
  • 34. This Enzyme Expressed only in Liver, Kidney and Intestine.
  • 35. • Steps Involve in Glycogenolysis : • 1. Breaking of Alpha- 1,4 Linkages: • Glycogen Phosphorylase Cleave the alpha 1,4 Linkage. • Release Glucose 1 Phosphate Not Free Glucose. • Glycogen Phosphorylase Stop its action when it is at least 4 glucose residue remain on Branch chain. • 2. Removal Of Branches : • 1. First Part is a Alpha- 1,4 alpha 1,4 Glucan Transferase : • - Transfer trisaccharide residue to another forming a new alpha 1,4 linkage.
  • 36. • 2. Second part is alpha- 1,6 Glucosidase ( Amylo - 1,6 Glucosidase ) • Hydrolyses The Branching point. • Release Free Glucose Not Glucose 1 phosphate. • 3. Conversion of Glucose 1 phosphate to Free Glucose : • Glucose 1 phosphate converted into Glucose 6 Phosphate by Phosphoglucomutase. • Glucose 6 phosphate convert into Glucose By Glucose 6 phosphatase (Liver, Kidney)
  • 37.
  • 38.  Minor Pathways Of Carbohydrate Metabolism : 1. HMP Shunt / Pentose Phosphate pathway : • Pentose phosphate pathway is also called Hexose monophosphate pathway/ HMP shunt/ Phospho-gluconate pathway. • It is an alternative route for the metabolism of glucose. • It is more complex pathway than glycolysis. It is more anabolic in nature. • It takes place in cytosol. The tissues such as liver, adipose tissue, adrenal gland, erythrocytes, testes and lactating mammary gland are highly active in HMP shunt. • It concern with the biosynthesis of NADPH and pentoses.
  • 39. • Importance of Pentoses :- 1) The pentose and its derivatives are used for the synthesis of nucleic acids(DNA, RNA) & many nucleotides(ATP, NAD+, CoA). 2) When an organism growing on pentose sugar(5c), this pathway is used to produce carbohydrates for cell wall synthesis.
  • 40.
  • 41. 2. Uronic acid Pathway :- 1. An alternative oxidative Pathway for Glucose. 2. UDP Glucose converted to UDP Glucuronic acid (Glucuronate) by Using NAD. 3. No ATP is Formed. 4. Site – Liver 5. Organelles – Cytosol
  • 42. 3. Fructose Metabolism : •Fructose is an abundant sugar in the human diet. •This dietary monosaccharide is present naturally in fruits and vegetables, either as free fructose or as part of the disaccharide sucrose, and as its polymer inulin. •Sucrose (table sugar) is a disaccharide which when hydrolyzed yields fructose and glucose. •The metabolism of fructose from dietary sources is referred to as fructolysis.
  • 43. 4. Galactose Metabolism : • Galactose (galacto- + -ose, "milk sugar") sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C4 epimer of glucose. A galactose molecule linked with a glucose molecule to form a lactose molecule. • Galactan is a polymeric form of galactose found in hemicellulose, and forming the core of the galactans, a class of natural polymeric carbohydrates.
  • 44.
  • 45. • References : 1. Carbohydrates and Glycobiology by Lehninger’s principles of Biochemistry by David L. Nelson and Michael M. Cox, Chapter 7 pg. no. 239-267 . 2. www.wikipedia.org 3. Book of Biochemistry by U. Satyanarayana, and U. Chakrapani 3rd Edition, Section 3 pg.no. 244- 284. 4. Illustrated Biochemistry – Harper’s 26 th edition Pg. no. 130- 163. 5. Self assessment and Review of Biochemistry By Rebecca James, 4 th Edition 2018, Forewords by Gobind Garg, Devesh Mishra, Apurv Mehra pg. no. 142 - 186