Biohemistry

Metabolism of carbohydrate

Carbohydrate metabolism

  • Carbohydrates are the major source of energy in living cells.
  • The monosaccharide glucose is the central molecule in carbohydrate metabolism since all the major pathways of carbohydrate metabolism are connected with it.
  • The glucose is synthesized form non-carbohydrate precursors and it stored in the form of glycogen, when the body is required glucose it release from the glycogen.

Major pathways of carbohydrate metabolism

  1. Glycolysis (Embden-Meyerhof pathway)
    • The oxidation of glucose to pyruvate and lactate.
  2. Citric acid cycle (Krebs cycle or tricarboxylic acid cycle)
    • The oxidation of acetyl CoA to carbohydrate
    • It is the final common oxidative pathway for carbohydrates, fats, or amino acids, through acetyl CoA.
  3. Gluconeogenesis
    • Synthesis of glucose from non-sugar precursors, such as amino acids, glycerol, etc.
  4. Glycogenesis
    • Conversion of glucose to glycogen
  5. Glycogenolysis
    • The breakdown of glycogen to glucose.
  6. Hexose monophosphate shunt (pentose phosphate pathway or direct oxidative pathway)
    • This pathway is an alternative to the glycolysis and the TCA cycle for the oxidation of glucose.
  7. Uronic acid pathway
    • This pathway is also an alternative oxidative pathway for glucose.
    • It catalyzes the conversion of glucose to glucuronic acid, ascorbic acid, and pentoses.
  8. Galactose metabolism
    • The conversion of galactose to glucose and the synthesis of lactose.
  9. Fructose metabolism
    • The oxidation of fructose to pyruvate and the relation between fructose and glucose metabolism.
  10. Amino sugar and mucopolysaccharide metabolism
    • The synthesis of amino sugars and other sugars for the formation of mucopolysaccharides and glycoproteins.

Glycolysis

  • Glycolysis is defined as the sequence of reactions converting glucose (or glycogen) to pyruvate (Aerobic) or lactate (Anaerobic), with the production of ATP.
  • The complete pathway of glycolysis was elucidated in 1940.
  • Also referred to as Embden-Meyerhof pathway (E.M. pathway).

Salient features

  • Glycolysis takes place in all cells of the body. The enzymes of this pathway are present in the cytosomal fraction of the cell.
  • Glycolysis occurs in the absence or presence of oxygen i.e. aerobic and anaerobic.
  • Aerobic condition formed pyruvates and anaerobic condition formed lactate.
  • It is a major pathway for ATP synthesis in tissues lacking mitochondria.
  • In glycolysis pathway many intermediate branch pathway occurs so that glycolysis are useful for the synthesis of amino acids and fat.

Reactions of glycolysis

A. Energy investment phase

  1.  
    • Glucose is phosphorylated to glucose 6 – phosphate by hexokinase or Glucokinase.
    • Hexokinase is present in almost all the tissue and Glucokinase is found in the liver.
    • Hexokinase catalyzed the phosphorylation of various hexose i.e. fructose, mannose, etc. but Glucokinase catalyzed phosphorylation of only glucose molecules.
    • It is an irreversible reaction dependent on ATP and Mg2+.
    • Glucose 6 – phosphate is impermeable to the cell membrane.
    • It is a central molecule with a variety of metabolic fates i.e. glycolysis, glycogenesis, gluconeogenesis, and pentose phosphate pathway.
  2.    
    • Glucose 6-phosphate undergoes isomerization to form fructose 6-phosphate in the presence of the enzyme phosphohexose isomerase and Mg2+.
  3.   
    • Fructose 6-phosphate is phosphorylated to fructose 1, 6-bisphosphate by phosphofructokinase (PFK).
    • This is an irreversible and regulatory step in glycolysis.

B. Splitting phase

4.

  • The 6 carbon compound split into 2 three-carbon compounds.
  • Glucose 1, 6 – biphosphate is split to dihydroxyacetone phosphate and glyceraldehyde 3 – phosphate by the enzyme aldolase (fructose 1, 6- bisphosphate aldolase).

5.

  • Glyceraldehyde 3-phosphate and dihydroxyacetone phosphate undergo reversible interconversion by the enzyme phosphotriose isomerase. Thus, two molecules of glyceraldehyde 3-phosphate are obtained from one molecule of glucose.
  • The further process will involve two molecules of compounds.

C. Energy generation phase

6.

  • Glyceraldehyde 3 – phosphate yield high molecular compound 1, 3-bisphosphoglycerate in presence of enzyme glyceraldehyde 3 – phosphate dehydrogenase. This is the very important stage as it is involved the formation of f NADH + H+.
  • Inhibitor: Iodoacetate and arsenate.
  • In aerobic condition, NADH passes through the electron transport chain and 6 ATP are synthesized by oxidative phosphorylation.

7.

  • 1, 3-bisphosphoglycerate is converted to 3-phosphoglycerate with the enzyme phosphoglycerate kinase.
  • This step is called as subtract level phosphorylation and resulting in the synthesis of ATP without involvement of electron transport chain.
  • Phosphoglycerate kinase reaction is reversible.

8.

  • 3-Phosphoglycerate is converted to 2-phosphoglycerate by phosphoglycerate mutase. This is an isomerization reaction.

9.

  • The high energy compound phosphoenol pyruvate is generated from 2-phosphoglycerate by the enzyme enolase.
  • This enzyme requires Mg2+ or Mn2+ and is inhibited by fluoride.

10.

  • The last steps of aerobic condition in the presence of enzyme pyruvate kinase to form pyruvate.
  • It is the high energy phosphate from phosphoenolpyruvate to ADP, leading to the formation of ATP.
  • This step is also called subtract level phosphorylation and this reaction is irreversible.

Conversion of pyruvate to lactate

  • Under anaerobic conditions, pyruvate is reduced by NADH to lactate in presence of the enzyme lactate dehydrogenase.
  • The NADH utilized in this step is obtained from the reaction catalyzed by glyceraldehyde 3-phosphate dehydrogenase.
  • The formation of lactate allows the regeneration of NAD+ which can be reused by glyceraldehyde 3-phosphate dehydrogenase so that glycolysis proceeds even in the absence of oxygen to supply ATP.

Calculation of ATP

Method of enzyme synthesisNumber of ATP synthesized
Glyceraldehyde 3-phosphate dehydrogenase (2 NADH, ETC, oxidative phosphorylation)6(5)
Phosphoglycerate kinase (substrate level phosphorylation)2
Pyruvate kinase (substrate level phosphorylation)2
Two ATP are consumed in the reactions catalysed by hexokinase and phosphofructokinase-2
Net ATP synthesis in glycolysis in aerobic condition8(7)

Hello! My name is Smrutiranjan Dash, a pharmacy professional. belonging from, Bargarh, Odisha. I have acquired Master degree in Pharmacy (Pharmacology) form B.P.U.T, Rourkela, Odisha. Presently I am working as an Assistant Professor at The pharmaceutical college, Barpali.

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