CARBOHYDRATE METABOLISM EMP.pdf

CARBOHYDRATE METABOLISM GLYCOLYSIS (EMP Pathway) GLYCOLYSIS  The glycolytic pathway is also called the Embden-Meyerhof Pathway (EM Pathway) and is employed by all tissues for the utilization of glucose to generate energy (in the form of ATP) and intermediates for other metabolic pathway...

CARBOHYDRATE METABOLISM GLYCOLYSIS (EMP Pathway) GLYCOLYSIS  The glycolytic pathway is also called the Embden-Meyerhof Pathway (EM Pathway) and is employed by all tissues for the utilization of glucose to generate energy (in the form of ATP) and intermediates for other metabolic pathways. Pyruvate is the end product of glycolysis in cells with mitochondria in an adequate supply of oxygen.  In anaerobic glycolysis, the glucose is converted to pyruvate, which is reduced by NADH to form lactate and there is no net formation of ATP.  Aerobic glycolysis yields net 8 molecules of ATP per molecule of glucose, whereas anaerobic glycolysis results in net 2 molecules of ATP generation from one molecule of glucose. GLYCOLYTIC PATHWAY  Glycolysis, a series of ten reactions that occur in the cytoplasm, is a process in which one glucose molecule is converted into two molecules of pyruvate. The glycoly tic pathway comprises of two stages: 1. In the first phase, energy is utilized in the synthesis of phosphorylated form of glucose. 2. In the second phase, energy is generated in the form of ATP. 8 molecules of ATP are produced per molecule of glucose metabolized when pyruvate is the end product and only 2 mólecules of ATP are produced per molecule of glucose metabolized when lactate is the end product. FIRST PHASE 1. PHOSPHORYLATION OF GLUCOSE- Glucose is converted to glucose-6-phosphate since phosphorylated intermediates do not readily penetrate cell membrane and this commits glucose to further metabolism in the cell. Hexokinase catalyses this irreversible reaction in most tissues and in liver; glucokinase is the predominant enzyme for the phosphorylation of glucose. 2. Isomerization of glucose-6-phosphate: This step is catalyzed by phosphoglucoisomerase to form fructose-6-phosphate. This is' a reversible reaction  Phosphorylation of fructose-6-phosphate: This is an irreversible reaction, catalyzed by phosphofructokinase (PFK- I) a most important regulatory enzymes of glycolysis. PFK-1 is activated by high concentrations of AMP and fructose-2,6- bisphosphate. ATP is converted to ADP.  Cleavage of fructose-l,6-bisphosphate: Aldolase cleaves fructose-1,6-bisphosphate to dihydroxyacetone phosphate and glyceraldehyde-3-phosphate in the reversible reaction  Isomerization of dihydroxyacetone phosphate: Triosephosphate isomerase interconverts dihydroxyacetone phosphate and glyceraldehyde-3- phosphate. Dihydroxyacetone phosphate must be isomerized to glyceraldehyde-3- phosphate for further metabolism in the glycolytic sequence. This isomerization results in the production of two molecules of glyceraldehyde-3- phosphate from the cleavage of fructose- l,6-bisphosphate. SECOND PHASE  OXIDATION OF GLYCERALDEHYDE-3-PHOSPHATE: The conversion of glceraldehyde- 3-phosphate to 1,3-bisphosphoglycerate is catalysed by glyceraldehyde- 3-phosphate dehydrogenase and the required cofactors are NAD' and Pi. The NADH formed is reoxidized either via the respiratory chain or by the NADH linked conversion of pyruvate to lactate. The high-energy phosphate group at carbon 1 of 1,3-bisphosphoglycerate conserves much of the free energy produced by the oxidation of glyceraldehyde-3-phosphate.  FORMATION OF ATP FROM 1,3-BIPHOSPHOGLYCERATE and ADP: The high-energy phosphate group of 1,3- biphosphoglycerate is used to synthesise ATP from ADP catalysed by phosphoglycerate kinase and is a reversible reaction. The reaction product is 3-phosphoglycerate. Two molecules of ATP are produced since two molecules of 1,3-biphosphoglycerate are formed from one molecule of glucose.  SHIFT OF THE PHOSPHATE GROUP FROM CARBON 3 TO CARBON 2: This reversible reaction is catalyzed by phosphoglycerate mutase.  DEHYDRATION OF 2-PHOSPHOGLYCERATE: Enolase causes dehydration of 2- phosphoglycerate to phosphoenol pyruvate.  FORMATION OF PYRUVATE: Pyruvate kinase converts phosphoenolpyruvate to pyruvate in this irreversible reaction with the release of high-energy phosphate to form ATP. This is the 2nd example of substrate level phosphorylation. This is one of the regulatory sites of glycolysis. Pyruvate kinase is an enzyme activated by fructose-1,6-bisphosphate and inactivated by glucagon via cyclic AMP. ENERGY PRODUCTION IN GLYCOLYSIS