Dental Biochemistry 2015 Lecture 9 - Glycolysis

1. Dental Biochemistry 2015Lecture 9 - Glycolysis Michael Lea

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

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

4. 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.

5. 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.

8. 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.

12. 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 pH.

14. 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 GLUT4 and this is particularly important for muscle and adipose tissue.

15. 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.

16. 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.

17. 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