Module 7: V4 - V6 Flashcards
What are the recurring motifs in regulation?
compartmentalisation: where do the reactions occur?
allosteric regulation: enzymes catalysing committed and usually irreversible steps
organ specialisation: compared metabolism of brain, liver, muscle and adipose
covalent regulation and enzyme levels (hormonal regulation)
What is the definition of allosteric?
of or involving a change in the shape and activity of an enzyme that results from the binding of a regulatory molecule at a site other than the active site
What are irreversible steps equivalent to?
control points e.g. three irreversible steps in glycolysis
Why don’t allosteric enzymes display Michaelis-Menten kinetics?
this is because an allosteric enzyme can exist in either the T-state or the R-state and various factors will determine the proportion of these states
When will allosteric enzymes display Michaelis-Menten kinetics?
if the T-state or R-state is isolated
Which irreversible step of glycolysis does PFK-1 catalyse?
conversion of fructose-6-phosphate to fructose-1,6-biphosphate
Which modulators are used in allosteric regulation of PFK-1?
ATP and citrate are allosteric inhibitors of PFK-1
AMP, ADP and F-2,6-bisP are allosteric activators of PFK-1
Which state of an enzyme do allosteric inhibitors stabilise?
the T-state
Which state of an enzyme do allosteric activators stabilise?
the R-state
Where is F-2,6-BP production regulated?
in the liver and muscle (regulated differently between each of these locations)
Which inhibitors are used in allosteric regulation of hexokinase?
by the product of the reaction it catalyses which is glucose-6-phosphate
Which modulators are used in allosteric regulation of pyruvate kinase?
liver and muscle L-PK:
inhibited by ATP4- and alanine
activated by F-1,6-bisP
What is the difference between liver and muscle pyruvate kinase?
liver pyruvate kinase can undergo covalent modification muscle pyruvate kinase cannot
What is the major fuel for the human brain?
glucose
When can the brain adapt to ketone bodies? When does danger occur?
during starvation (> 3 days) danger occurs when [glucose] < 2.2 mM
What is the implication of the brain lacking fuel stores?
relies on a constant supply of blood glucose (via GLUT3, Km ~ 1.0 mM)
What does the brain consume at resting conditions?
60% of total gluconeogenesis glucose = 120 g/day
How much glycogen is stored in muscle?
75% of total body glycogen
can represent 1% of muscle weight after a meal (other 25% stored in liver)
What is the major fuel source in the resting state?
muscle utilises fatty acids (85% of energy)
What does the heart muscle use in preference to glucose?
ketone body, acetoacetate
How are muscle and liver metabolites connected?
by the Cori cycle
Why does adipose require glucose?
to perform major task of synthesising and storing triacylglycerol, which is mobilised during fasting
How much of total available energy does adipose store?
> 80%
How active is adipose during starvation? What results in this level of activity?
highly active as decreased insulin activates hormone-sensitive lipase which breaks down TAG
What can the liver utilise as fuel sources?
glucose, fatty acids, ketone bodies and amino acids
What does the liver prefer as a fuel source?
ɑ-keto acids derived from the degradation of amino acids in preference to glucose
How much of total body glycogen does the liver store?
1/4 of total body glycogen
How does the liver make 200g of glucose per day?
via gluconeogenesis (GNG) using lactate and alanine from muscle, glycerol from adipose and glucogenic amino acids from diet
How active is the liver during starvation?
highly active making glucose via GNG to maintain blood [glucose] primarily for the brain and RBCs + oxidises FAs for energy / formation of ketone bodies for the brain, heart muscle and other tissues
What are other functions of the liver?
synthesises TAGs, PLs and cholesterol and secretes as VLDL for lipoprotein transport and synthesises heme (altruistic organ)
What are the key differences between uncompetitive inhibition and allosteric regulation?
allosteric regulation involves modulators which bind non-covalently to the allosteric site and can result in either an ↑ or ↓ in binding to S
uncompetitive inhibition only involves molecules which ↓ binding to S + uncompetitive inhibitors can also bind irreversibly to the active binding site
Why can’t you describe the midpoint of an allosteric kinetics curve with a Km value?
this is because an allosteric kinetics curve is sigmoidal, not hyperbolic
ATP is a substrate and an allosteric inhibitor of PFK-1. How can that be and why would that be advantageous?
this is because ATP has a phosphate group which it can donate in enzymatic reactions
advantageous as it allows enzymes to phosphorylate molecules
