Biochemistry Exam 4 - Metabolic Control Mechanisms

Front 1

Control of Amount of Active Enzyme

Back 1

1) Tissue Characteristics
-differentiation due to differential gene expression; organs have different metabolic roles

2) Alterations in rate of protein synthesis and/or breakdown (Major Site of Regulation)

Front 2

Control of Amount of Substrate

Back 2

1) Transport
a) membranes cause compartmentalization
b) selective permeability properties exist in a given membrane type due to expression of specific transporters
c) substrate concentration < Km and therefore in the first order range (changes in concentration cause changes in reaction rate)

2) Interactions with other metabolic systems
- branch points; can drain or replenish substrate levels thereby altering enzyme activity

Front 3

Non-covalent Mechanisms (allosteric) which affect protein activity

Back 3

1) readily reversible
2) dependent on presence & concentration of modifiers
3) rapid --> seconds

Front 4

Effects of Catalytic Activity at Constant Enzymatic & Substrate Concentrations

Back 4

1) Activators & Inhibitors (Allosteric) --> Major Site of Regulation
2) Modification of Catalytic capacity of enzymes (active-inactive conversions) --> Major Site of Regulation
3) Environmental (pH, osmotic effects, etc.)

Front 5

Covalent Mechanisms which affect Protein Activity

Back 5

1) Stable, not readily reversible
2) Usually require 2 enzymes, one to add the group & one to remove it
-Exception to this is proteolytic modification which is completely IRREVERSIBLE
3) Moderately Fast --> minutes

Ex. Proteolytic Modification
a) conversion of precursor to active forms; this is a very improtant mechanism in blood clotting, in peptide hormone synthesis, and in digestion
b) Inactivation of enzymes via proteolytic digestion (degradation, turnover)

Front 6

Adenosylribosylation

Back 6

-catalyzed by ADP ribosyl transferases, which among others are important in the action of certain potent bilogical toxins (cholera, diptheria, & pertussis)

A) Mechanism
-transfer of ADP ribose from NAD to arginine ot other amino acid residues

B) Examples
-Guanyl nucleotide binding proteins of adenylate cyclase are ADP ribosylated by baterial toxins which have enzyme activity

Front 7

Cholera Toxins

Back 7

-activates Gs
-catalyzes the ADP ribosylation of Gs & some other G proteins

Front 8

Pertussis Toxin

Back 8

-inhibits Gi

Front 9

Gs Protein

Back 9

-turns on adenylate cyclase

Front 10

Gi Protein

Back 10

-turns off adenylate cyclase

Front 11

Source of ADP ribose

Back 11

NAD
-->nicotinomide is the product

Front 12

Phosphorylation

Back 12

-Phosphate from ATP (or GTP) is covalently attachems to serine, threonine, or tyrosine residue of proteins
-can cause a change in Km, Vmax, or in the sensitivity of the enzyme to an allosteric effector
-accomplished by --> PROTEIN KINASE

Front 13

cAMP - dependent protein kinase (protein kinase A, PKA)

Back 13

-PKA is activated by cAMP
-phosphorylates many different proteins