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2. CARBOHYDRATE METABOLISM :
Carbohydrate break down to monosaccharides and absorbed into blood stream . In liver and muscles glucose gets converted to
glycogen by process of glycogenesis .(anabolism ) .and this glycogen gets stored in liver and muscle until needed.
When blood glucose level gets low , 2 hormones epinephrine and glucagon gets secreted to stimulate and convert glycogen to
glucose .and this process of conversion of glycogen to glucose is called glycolysis (catabolism ) .the end products are pyruvic acid
and ATP. Since glycolysis release less ATP , reaction gets continue to convert pyruvic acid to acetyl CoA and then citric acid in citric
acid cycle .majority of ATP is made from oxidation in citric acid cycle in connection of Electron transport chain.
During muscular activity ,pyruvic acid is converted into lactic acid instead of acetyl CoA .During rest lactic acid gets converted to
pyruvic acid ,this pyruvic acid gets converted to glucose with process is called gluconeogenesis.(anabolism ) .if body doesn’t need
glucose ,then it converted to glycogen by glycogenesis.
FOR DIAGRAM REF PAGE 145 CARBOHYDRATE SUMMARY
3.
4. GLYCOLYSIS : The glycolytic pathway is called Embeden –Meyerhof pathway (EM pathway ) .all tissue get involved in this process
of utilizing glucose to generate energy and intermediate for other metabolic pathway .
Pyruvate is the end product of glycolysis ,in cell with mitochondria and supply of oxygen .there is 2 types of glycolysis :
1. Aerobic glycolysis : here the oxygen is needed to reoxidise NADH formed during oxidation of glyceraldehyde -3-phosphate .It
yield 8 ATP .
2. Anaerobic glycolysis : the glucose gets converted to pyruvate that is reduced by NADH to form lactate and there is no net
information of ATP .It yield 2 ATP anaerobic glycolysis allows the continued production of ATP .in tissues that lack mitochondria.
GLYCOLYTIC PATHWAYS
Glycolysis is series of 10 reaction that convert glucose molecule into 2 molecule of pyruvate .the glycolytic pathway has two stages :
1.The synthesis of phosphorylated form of glucose where energy is being utilized.
2.In this stage ,energy gets generated in the form of ATP .when pyruvate is end product ,the 8 molecule of ATP gets generated per
glucose molecule metabolized . and when lactate is end product 2 ATP molecule are produced per glucose molecule metabolized.
First phase :
1. synthesis of phosphorylated form of glucose ,
2. isomerization of glucose 6 phosphate ,
3. phosphorylation of fructose 6 phosphate ,
4. cleavage of fructose 1,6 bisphosphate .
5. Isomerisation of dihydroxyacetone phosphate..
5. Phosphorylation of glucose : as phosphorylated intermediate do not penetrate the cell membrane so the glucose gets converted
to glucose 6 phosphate .in tissues hexokinase catalyze this irreversible reaction and in liver Glucokinase is predominate enzyme
.hexokinase is allosteric enzyme that is inhibited by glucose 6 phosphate
Hexokinase exist in many isozyme forms and can act upon by aldose or keto hexose but has low Km that means it has high affinity
for glucose .Glucokinase have high Km for glucose and is not inhibited by glucose 6 phosphate and is induced in body by
carbohydrate rich diet and insulin.
Isomerization Of Glucose 6 Phosphate : The Enzyme phosphoglucoisomerase catalyze this process and form fructose 6
phosphate .this is reversible reaction.
Phosphorylation of fructose 6 phosphate: the enzyme phosphofructokinase (PFK-1)T catalyze this irreversible reaction. This
enzyme gets activated by high concentration of AMP and fructose 2,6-biphosphate .the inhibitors are Citrate and ATP.
Cleavage of fructose 1,6 bisphosphate : fructose 1,6 bisphosphate gets cleaved to dihydroxyacetone phosphate and
glyceraldehyde 3 phosphate with the help of aldolase (enzyme) and is a reversible reaction .
Isomerization of dihydroxyacetone phosphate :trisphosphate isomerase interconverts dihydroxyacetone phosphate and
glyceraldehyde 3 phosphate .for further metabolism in glycolytic sequence dihydroxyacetone phosphate must be isomerized to
glyceraldehyde 3 phosphate and this isomerization results in formation of 2 molecules of glyceraldehyde 3 phosphate from fructose
1,6 bisphosphate
6. SECOND PHASE : This stage is energy producing stage from triose phosphate to pyruvate .
1.Oxidation of glyceraldehyde 3 phosphate
2. Formation of ATP from 1,3 bisphosphoglycerate and ADP
3.Shift of phosphate group from carbon 3 to carbon 2
4. Dehydration of 2- phosphogycerate
5.Formation of pyruvate
1. Oxidation of glyceraldehyde 3 phosphate :
Glyceraldehyde 3 phosphate dehydrogenase convert glyceraldehyde 3 phosphate to 1,3 bisphosphogycerate .this reaction require
cofactor NAD+ and Pi .NADH is reoxidised via respiratory chain for by NADH linked conversion of pyruvate to lactate . the energy
produced by oxidation of glyceraldehyde 3 phosphate conserve by high energy phosphate group at carbon 1 of 1,3 –
bisphosphoglycerate .this reaction is an example of substrate level phosphorylation where the production of high energy phosphate
is coupled directly to oxidation of substrate
2. Formation of ATP from 1,3 bisphosphoglycerate and ADP :
The high energy phosphate group of 1,3 biphosphogycerate is used to synthesize ATP From ADP catalyzed by phosphoglycerate
kinase and this is reversible reaction .the product formed is 3-phosphoglycerate and 2 molecules of ATP are formed.
Other way to form 3-phosphoglycerate :
1,3 bisphosphoglycerate is converted to 2,3 –bisphosphoglycerate (BPG) by the action of bisphosphoglycerate mutase which is
present in erythrocyte .2,3 bisphosphoglycerate is hydrolyse to 3 phosphogycerate by phosphatase .and no ATP is formed..it provide
2,3 –BPG that bind hb and decrease it affinity for oxygen .
7. 3. Shift of phosphate group from carbon 3 to carbon 2 : this is reversible reaction catalyzed by phosphoglycerate mutase .
4 .Dehydration of 2-phosphoglycerate :Enolase causes dehydration of phosphoglycerate to phosphoenol pyruvate .
5. Formation of pyruvate : Pyruvate kinase converts phosphoenolpyruvate to pyruvate .it is irreversible reaction and and release
high energy phosphate and form ATP .This is also an example of substrate phosphorylation .pyruvate kinase gets activated by
fructose 1,6 bisphosphate and inactivated by glucagon. ATP ,ALANINE ,fatty acids are also the inhibitors .
Now the first and second phase comprises of 10 steps together
FATE OF PYRUVATE :
Pyruvate has 3 different fates :
First fate :Under aerobic conditions ,pyruvate enters mitochondria and get converted to acetyl CoA . Acetyl CoA enters citric acid
cycle and it enters ETC where oxidation is completed and ATP is synthesized .
Second fate : under anaerobic conditions pyruvate is converted to lactate .
Third fate : In some organisms pyruvate gets converted to ethanol.
In all process ,NAD+ regenerated so that the glycolysis continues
FATE I : Formation of lactate and its consumption : reoxidation of NADH through the respiratory chain is prevented in anaerobic
conditions .regeneration of NAD+ from NADH is carried out by the action of lactose dehydrogenase on pyruvate resulting in lactate
and NAD+ and this allows the glycolytic cycle to continue even in absence of oxygen .the tissue that work under hypoxic condition
produce lactate .here is the advantage of using pyruvate for reoxidation of NADH coz pyruvate is the end product of glycolysis and
is readily available in cells
8. In exercising skeletal muscle ,lactate accumulate which is released in the blood and is taken by liver to convert it into glucose .this
process is called gluconeogenesis .in liver and heart ,the ratio of NADH/NAD is lower than in exercising muscle. These tissues
oxidize lactate to pyruvate .in liver ,pyruvate either converted to glucose by gluconeogenesis or oxidized in citric acid cycle.in hear
, lactate get oxidized to CO2and H20 via citric acid cycle .glycolysis in erythrocyte always results in lactate even under aerobic
conditions coz erythrocytes lack mitochondria .
Fate II : pyruvate get converted to acetyl CoA .
Oxidative decarboxylation of pyruvate : in cardiac muscle pyruvate gets converted to acetyl CoA .,Major fuel of citric acid cycle .
and building block of fatty acid synthesis .besides oxygen , it needs mitochondria participation withfunctional electron transport
chain .
Fate III : pyruvate related to microorganisms . In yeast and microorganism the carboxylation of pyruvate by pyruvate
decarboxylase to form ethanol .but it doesn’t occur in humans.6843141