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Flashcards in Regulation of enzymes Deck (26):
1

Regulation of enzymes by... (2)

-by changing the concentration of enzyme
-by changing the conformation of the active site

2

Regulation of enzymes
-by changing the concentration of enzyme (2)

-enzyme synthesis
-enzyme degradation

3

Regulation of enzymes
-by changing the conformation of the active site (4)

-proteolytic cleavage,
-allosteric regulators,
-covalent modification,
-protein–protein interactions

4

The rate of reaction is proportional to..

the amount of enzyme present

5

Regulation of enzyme quantity

The absolute quantity of an enzyme reflects the net balance between its rate of synthesis and its rate of degradation.

6

Regulated enzyme synthesis
-regulated by...
-slow or fast?
-synthesis of certain enzymes depends upon...
-other characteristics

-increasing (induction) or decreasing (repression) the rate of gene transcription.
-usually slow.
-the presence of inducers
-excess of a metabolite may slow synthesis by repression
-Both induction and repression involve cis elements, specific DNA sequences located upstream of regulated genes, and transacting regulatory proteins.

7

Regulated enzyme synthesis
-Steps

1.Protein synthesis begins with the process of gene transcription, transcribing the genetic code for that protein from DNA into messenger RNA.
2.The code in messenger RNA is then translated into the primary amino acid sequence of the protein.

8

Regulated Protein Degradation

-All proteins in the cell can be degraded with a characteristic half-life within lysosomes.
-And by highly selective and systems, proteosomes and caspases.

9

Allosteric effectors (activators and inhibitors)
-definition
-function

-compounds that bind to the allosteric site (a site separate from the
catalytic site).
-They cause a conformational change that affects the affinity of the enzyme for the substrate.

10

Advantages of Allosteric effectors (4)

-Allosteric inhibitors have a much stronger effect on enzyme velocity than inhibitors in the active catalytic site.
-Allosteric effectors do not occupy the catalytic site, they may function as activators.
-The effect is rapid
-These features are essential for feedback regulation of metabolic pathways.

11

Covalent modification
-The activity of many enzymes is regulated through .... by ..... or ... by ....

-phosphorylation by a protein kinase
-dephosphorylation by a protein phosphatase

12

Phosphorylation (4)

-Serine/threonine protein kinases transfer a phosphate from ATP to the hydroxyl group of a specific serine on the target enzyme;
-Phosphate creates conformation change at the catalytic site.
-The conformational change makes certain enzymes more active and other enzymes less active.
-The effect is reversed by a specific protein phosphatase that removes the phosphate by hydrolysis.

13

Phosphate
-characteristics

It is a bulky, negatively charged residue that interacts with other nearby amino acid residues of the protein to create a conformational change at the catalytic site.

14

Protein kinase A (4)

-It is a serine/threonine protein kinase.
-It phosphorylates a number of enzymes that regulate different metabolic pathways.
-Provides a means for hormones to control metabolic pathways.
-increase the intracellular concentration of the allosteric regulator cAMP (hormonal second messenger)

15

Conformational changes from Protein- Protein interactions

Modulator proteins
-they are protein allosteric effectors.

-ex: small G proteins

16

Modulator proteins
-function
-it performs its function by...

bind to other proteins and regulate their activity:

-By causing a conformational change at the catalytic site.
-By blocking the catalytic site.

17

Proteolytic cleavage

-enzymes that are secreted as proenzymes need to undergo proteolytic cleavage to become fully functional
-it is irreversible
-zmogens
-ex: proteolytic enzymes of the stomach and pancreas.

18

Zymogens

the precursor proteins of proteases (enzymes that cleave specific peptide bonds).


-proteolytic cleavage

19

Regulation of metabolic pathways
-rate limiting step (3)

-Regulatory enzyme, catalyzes the rate- limiting step in the pathway.
-slowest step and is usually not readily reversible.
-changes in the rate-limiting step can influence flux through the rest of the pathway.

20

Regulation of metabolic pathways
-feedback regulation (3)

-situation in which the end-product of a pathway controls its own rate of synthesis.
-involves allosteric regulation of the rate-limiting enzyme by the end-product of a pathway.
-The end-product of a pathway may also control its own synthesis by inducing or repressing the gene for transcription of the rate- limiting enzyme in the pathway

21

Regulation of metabolic pathways
-feed- forward regulation

-ex: in disposal of toxic compounds
-occur through an increased supply of substrate to an enzyme with a high Km.
-allosteric activation of a rate-limiting enzyme through a compound related to substrate supply

22

Counter- regulation of opposing pathways

-the pathway for synthesis of a compounds usually differs from the pathway of the degradation of that compound.
-a pathway can therefore have a different regulatory enzyme than the opposing degradative pathway.
-one pathway can be activated while the other is inhibited.

Ex: glycogen synthesis is activated while glycogen degradation is inhibited.

23

Compartmentation of enzymes

1.Into multi-enzyme complexes or organelles.
Ex: enzymes of the TCA cycle are all located within the mitochondrion.

2.Enzymes catalyzing sequential reactions into multi- enzyme complexes.
Intermediated of the pathway can be transferred from the active site on one enzyme to the active site on another enzyme.

24

Homeostasis involves...

maintaining a relatively constant intracellular and intraorgan environment despite wide fluctuations in the external environment.

25

Control of metabolite flux involves....

-changes in the concentration.
-changes in the catalytic activity

or both of an enzyme.

26

Feed- forward vs. Feed- back regulation

Forward --> through a compound related to substrate supply.

Back --> end- product of a pathway controls its own rate of synthesis