- 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
- Glycolysis (Embden-Meyerhof pathway)
- The oxidation of glucose to pyruvate and lactate.
- 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.
- Synthesis of glucose from non-sugar precursors, such as amino acids, glycerol, etc.
- Conversion of glucose to glycogen
- The breakdown of glycogen to glucose.
- 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.
- 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.
- Galactose metabolism
- The conversion of galactose to glucose and the synthesis of lactose.
- Fructose metabolism
- The oxidation of fructose to pyruvate and the relation between fructose and glucose metabolism.
- Amino sugar and mucopolysaccharide metabolism
- The synthesis of amino sugars and other sugars for the formation of mucopolysaccharides and glycoproteins.
- 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).
- 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
- 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.
- Glucose 6-phosphate undergoes isomerization to form fructose 6-phosphate in the presence of the enzyme phosphohexose isomerase and Mg2+.
- 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
- 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).
- 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
- 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.
- 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.
- 3-Phosphoglycerate is converted to 2-phosphoglycerate by phosphoglycerate mutase. This is an isomerization reaction.
- 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.
- 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 synthesis||Number 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 condition||8(7)|