Lecture 24. Enzyme regulation

Friday 4 November 2016

Control of enzyme activity. Aspartate transcarbamoylase (ATCase) and allosteric control in enzymes. Control by covalent modification: Phosphorylation, kinases, and phosphatases. Drug design. Cytochromes P450.

Reading: VVP4e - Ch.12, pp.376-391.

---

Summary

There are numerous ways in which the activity of enzymes are regulated. More generally, the regulation of protein function by specific ligand interactions (including interactions with other proteins) and covalent modifications are key features in the organizational and control mechanisms of living organisms. The regulatory strategies we will consider are the following:

1. Allosteric control. Examples: Hemoglobin and aspartate transcarbamoylase (ATCase).

2. Multiple forms of enzymes ("isozymes")

3. Reversible covalent modification (Primary example: phosphorylation and dephosphorylation by kinases and phosphatases, respectively. The text discusses the example of glycogen phosphorylase, which is activated by phosphorylation)

4. Proteolytic activation (Examples: processing of proenzyme forms of digestive enzymes; blood clotting cascade - see zymogens)

Drug design

Historically, pharmacology has relied on empirical observations. More recently, as knowledge about biological function at the molecular level has accumulated, it has fostered attempts to exploit understanding of molecular mechanisms in development of therapeutic interventions. (12: 394-400)