Lecture 24. Glycolysis
Tuesday 23 April 2019
Overview and context of glycolysis. Stages of glycolysis. Details of glycolytic enzymes, reactions and mechanisms. The five steps of the first stage of glycolysis. Phosphorylation of glucose (hexokinase and glucokinase). Isomerization of glucose 6-phosphate (phosphohexose isomerase). Phosphorylation of fructose 6-phosphate (phosphofructokinase) and subsequent cleavage reaction (aldolase). Isomerization of triose phosphates (TIM). GAPDH couples oxidation to formation of a high-energy acyl phosphate. Phosphoglycerate kinase catalyzes the first substrate-level phosphorylation, forming ATP. Phosphoglycerate mutase and enolase produce another high-energy phosphorylated species, PEP. Pyruvate kinase catalyzes the second substrate-level phosphorylation, forming ATP. Fates of pyruvate.
Reading: Lehninger - Ch.14, pp.533-548.
Summary
Reading summary. §14.1 Glycolysis. An overview: Glycolysis has two phases. Fig.14-2: The two phases of glycolysis. Fig.14-3: The chemical logic of the glycolytic pathway. Fates of pyruvate. ATP and NADH formation coupled to glycolysis. Energy remaining in pyruvate. Importance of phosphorylated intermediates. The preparatory phase of glycolysis reqires ATP. 1. Phosphorylation of glucose. 2. Conversion of glucose 6-phosphate to fructose 6-phosphate. 3. Phosphorylation of fructose 6-phosphate to fructose 1,6-bisphosphate. 4. Cleavage of fructose 1,6-bisphosphate. 5. Intercoversion of the two triose phosphates. The payoff phase of glycolysis yields ATP and NADH. The overall balance sheet shows a net gain of ATP. Glucose uptake is deficient in type I diabetes mellitus.
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In the concluding lectures, we turn our attention to the central metabolic pathway of glycolysis. which takes place in the cytoplasm of cells. Pyruvate, the product of glycolysis, is transported into the mitochondrial matrix before it is oxidized by pyruvate dehydrogenase complex
Supplementary and additional resources: gluconeogenesis;
Phosphorylation of glucose
The steps of glycolysis beginning with glyceraldehyde 3-phosphate (GAP) can be viewed as a "second stage" of glycolysis involving a series of three-carbon intermediate metabolites. The enzyme triose phosphate isomerase (or TIM) completes the conversion of D-glucose into two three-carbon molecules of glyceraldehyde 3-phosphate (GAP). From that point GAP is converted in five steps to pyruvate. Pyruvate can be considered the end product of glycolysis, and it has a number of possible fates.