Dental Biochemistry 2015 Lecture 9 Glycolysis Michael Lea

Dental Biochemistry 2015 Lecture 9 - Glycolysis Michael Lea

Lecture Outline • • Function of glycolysis Metabolic sequence Rate limiting steps Distinction between anaerobic and aerobic glycolysis

Suggested Reading • Meisenberg and Simmons. Principles of Medical Biochemistry, 3 rd edition, pages 347 -353, 374 -379

Function of Glycolysis • The function of glycolysis is to convert glucose to three carbon compounds with the formation of ATP • Glycolysis occurs in all the cells of the body and the enzymes are located mainly in the cytosol.

Metabolic Sequence • Glycolysis is a sequence of ten reactions in which glucose is converted to pyruvate. • There is an initial requirement for ATP but glycolysis results in a net production of ATP. • There is one oxidative step in which NAD is reduced to NADH.

Hexokinases • The phosphorylation of glucose is catalyzed by hexokinases. • The predominant hexokinases in most tissues have a high affinity for glucose and will be saturated at circulating glucose concentrations • In liver and pancreatic islets there is a hexokinase with a high Km value (low affinity). This enzyme is called glucokinase. Fluctuations in circulating glucose concentration will affect the velocity of the reaction catalyzed by glucokinase.

Inhibition of Glycolysis by Fluoride • Fluoride inhibits the enzyme enolase and thereby decreases the production of lactic acid by glycolysis. • Note that fluoride also makes the calcium phosphate in teeth more resistant to solubilization at low p. H.

Rate-limiting Steps • Regulation is mainly exerted at the 3 essentially irreversible reactions catalyzed by hexokinase, phosphofructokinase and pyruvate kinase. • The most important rate-limiting step is that catalyzed by phosphofructokinase. • Phosphofructokinase is inhibited by high concentrations of ATP. • Note that the activity of glucose transporters (GLUTs) can affect the intracellular glucose concentration. Insulin increases the activity of GLUT 4 and this is particularly important for muscle and adipose tissue.

Distinction between anaerobic and aerobic glycolysis • Under anaerobic conditions in mammalian cells, pyruvate is reduced to lactate using NADH as the coenzyme. • Under aerobic conditions, pyruvate is oxidized to form acetyl coenzyme A which can be oxidized to yield carbon dioxide in the citric acid cycle.

Pasteur and Warburg Effects • The rate of glycolysis is usually greater under anaerobic conditions than aerobic conditions. The inhibition of glycolysis by oxygen is known as the Pasteur effect. • Cancer cells tend to have high rates of glycolysis and a decreased Pasteur effect. This common feature of cancer cells is known as the Warburg effect.

Lecture Objectives • After studying this lecture material you should be able to • Describe where glycolysis occurs • Explain the importance of glycolysis • Describe all the reactions of glycolysis particularly the 3 irreversible reactions, the formation of ATP and the NAD requiring reaction. • Identify the key regulated step • Explain the distinction between anaerobic and aerobic glycolysis