Principles of Biochemistry/Glycolysis

Glycolysis is the first step of glucose catabolism. Glycolysis is divided into two categories: aerobic (chemical reactions that occur with the presence of oxygen) and anaerobic (chemical reactions that do not require oxygen). An example of anaerobic glycolysis is fermentation. Glucose is the reactant; while ATP and NADH are the products of the Glycolysis reaction. There are three stages in an aerobic glycolysis reaction: 1) decarboxylation of pyruvate 2) Citric Acid Cycle (also known as the Krebs Cycle) 3) Electron transport chain. Glycolysis consists of a total of 10 chemical reactions that starts with the breakdown of glucose into pyruvate and NADH which takes place in the cytoplasm. Step 1: Phosphorylation of Glucose This reaction is irreversible under intracellular condition, transferase class Catalyzed by hexokinase-soluble and cytosolic protein (glucokinase in liver) Requires ATP, and Mg2+ as substrates, generates ADP ΔG′°= -16.7 kJ/mol Step 2: Conversion of Glucose 6-Phosphate to Fructose 6-Phosphate This reaction is reversible, isomerase class Catalyzed by phosphohexo isomerase Requires Mg2+ as a substrate ΔG′°= 1.7 kJ/mol Step 3: Phosphorylation of Fructose 6-Phospate to Fructose 1,6-Bisphosphate Irreversible reaction, transferase class Catalyzed by phosphofructokinase-1 which is highly regulate allosteric enzyme Requires ATP, and Mg2+ as substrates, generates ADP ΔG′°= -14.2 kJ/mol Step 4: Cleavage of Fructose 1,6-Bisphosphate Reversible reaction, lyase class Catalyzed by aldose Yields 2 different triose phosphates: G3P (an aldose), and DHAP (a ketose) ΔG′°= 23.8 kJ/mol Step 5: Interconversion of the Triose Phosphate Reversible reaction, isomerase class Catalyzed by triose phosphate isomerase ΔG′°= 7.5 kJ/mol Step 6: Oxidation of Glyceraldehyde 3-Phosphate to 1,3-Bisphosphoglycerate Reversible reaction, oxidoreductase class Catalyzed by glyceraldehyde 3-phosphate dehydrogenase Requires NAD+, yields NADH ΔG′°= 6.3 kJ/mol Step 7: Phosphoryl Transfer from 1,3-Bisphosphoglycerate to ADP Reversible reaction, transferase class Catalyzed by phosphoglycerate kinase Requires ADP and Mg2+, generates ATP ΔG′°= -18.5 kJ/mol Step 8: Conversion of 3-Phosphoglycerate to 2-Phosphoglycerate Reversible reaction, isomerase class Catalyzed by phosphoglycerate mutase Requires Mg2+ ΔG′°= 4.4 kJ/mol Step 9: Dehydration of 2-phosphoglycerate to Phosphoenolpyruvate Reversible reaction,, lyase class Catalyzed by enolase ΔG′°= 7.5 kJ/mol Step 10: Transfer of the Phosphoryl Group from Phosphoenolpyruvate to ADP Irreversible reaction, transferase class Catalyzed by pyruvate kinase Requires ADP, Mg2+, K+, generates ATP ΔG′°= -31.4 kJ/mol The product pyruvate first appears in enol form, then tautomerizes to keto form. The net reaction for Glycolysis is : Glucose+2ADP+2P1+2NAD+ --> 2 Pyruvate + 2ATP+2NADH+2H++2H2O Fermentation Glycolysis in fermentation occurs under anaerobic condition, thus, NAD+ has to be regenerated. In order to do obtain NAD+, pyruvate is reduced into ethanol or lactic acid. During fermentation, only 2 ATP per glucose are produced; therefore, it is not too efficient. There are two types of fermentation: 1) Alcohol fermentation which occurs in yeast and some bacteria and 2) Lactic acid fermentation which occurs in some fungi and bacteria, and muscles cells.