Mic 428 - Lecture# 11 Regulation of Gene Expression

1. Mic 428 - Lecture# 11 Regulation of Gene Expression Outline Requires review of Chapter 7 before coming to class. The complexity of regulation. Overview of regulation. Constitutive and inducible enzymes. Major modes of regulation in the cell: 1. Control of enzyme activity. Post translational control.

2. Mic 428 - Lecture# 11 Regulation of Gene Expression Outline Feedback inhibition. Allosteric regulation and rate-limiting enzymes. Types of allosteric regulation. Isoenzymes. 2. Control of the amount of enzyme present: transcriptional control and translational control (NEXT CLASS).

3. Complexity of regulation Hundreds of different enzymatic reactions happening simultaneously. Need to respond rapidly to changes in their environment. Complicated developmental pathways.

4. CONSTITUTIVE INDUCIBLE Some enzymes are needed in the same amount under any growth condition. Some enzymes are not permanently needed in the same amount under any growth condition.

5. Two major modes of regulation: Control of enzyme activity After the enzyme has been produced Post translational control Control of the amount of an enzyme At the level of transcription Next class At the level of translation

6. Overview of regulation The product of gene A is enzyme A, which is synthesized constitutively and carries out its reaction. Enzyme B is also synthesized constitutively but its activity can be inhibited. The synthesis of the product of gene C can be prevented by control at the level of translation. The synthesis of the product of gene D can be prevented by control at the level of transcription.

7. Regulation of enzyme activity Inhibiting enzyme activity: Enzymes are synthesized with full enzymatic activity and then the activity is reduced or inhibited by certain compounds in the cell. These compounds are usually related to the metabolic pathway in which the enzyme functions.

8. We have seen some of these cases. Do you remember any?

9. Feedback inhibition

10. Feedback inhibition of enzyme activity

11. How is it possible for the end product of a pathway to inhibit the enzyme that acts on a substrate quite unrelated to it? By means of allosteric regulation The regulated enzyme is referred to as the rate-limiting enzyme.

12. Mechanism of enzyme inhibition by an allosteric effector

13. In branched metabolic sequences, the beginning of each branch is often controlled allosterically

14. Feedback inhibition in a branched biosynthetic pathway

15. Types of allosteric regulation: 1. Simple feedback inhibition. 2. Concerted feedback inhibition. 3. Sequential feedback inhibition.

16. 1. Simple feedback inhibition.

17. 2. Concerted feedback inhibition. A B C D E F More than one metabolite interacts with the enzyme

18. 3. Sequential feedback inhibition. A Two or more metabolites interact with an enzyme B C F D G E H

19. Some biosynthetic pathways are regulated by isoenzymes that catalyze the same reaction but are subject to different regulatory controls.

20. The common pathway leading to the synthesis of the aromatic amino acids contains three isozymes. Each of these enzymes is specifically feedback-inhibited by one of the aromatic amino acids. Note how an excess of all three amino acids is required to completely shut off the synthesis of DAHP.

21. Processing of preproinsulin

22. Protein splicing