Integration and Control Pasco 2
Integration and Control Pasco 2
UNIVERSITY OF GHANA
(All ri ghts reserved)
I. (a) State reasons why the flux through a metabolic pathway needs to be regulated.
(10 points)
- Living systems are open systems with metabolic pathways which comprise equilibrium and non-equilibrium reactions.
- The presence of different energy fuels in different tissues, and different energy requirements at different (nutritional & physiological) states,
there is the need for metabolic regulation.
- Metabolic pathways are generally under hormonal and/or nervous control.
- Fuels flow from one organ to the other in other to meet needs of specific organs
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(b) What are the factors that control the rate of flux through the citric acid cycle.
(10 points)
1. Substrate availability (oxaloacetate, acetyl-CoA and NAD+)
2. Inhibition by accumulating products (succinyl-CoA, citrate and ATP).
3. Allosteric feedback inhibition of enzymes catalysing the early steps of the cycle.
(c) Name the key enzymes in citric acid cycle that are under regulation and indicate how
they are regulated. (10 points)
1. citrate synthase,
2. isocitrate dehydrogenase and
3. ketoglutarate dehydrogenase
Substrate availability for citrate synthase (acetyl-CoA and oxaloacetate) depends on:
1. The metabolic state of the cell and thus may limit the rate of citrate formation.
2. NADH, a product of isocitrate and -ketoglutarate dehydrogenases activity may accumulate
leading to inhibition of both enzymes at high NADH/NAD+ ratio.
3. ATP inhibits citrate synthase and isocitrate dehydro-genase.
....
2. What is the importance of metabolic regulation? Name three major junctions in
metabolism and state the importance of each junction in the integration of
metabolism. (15 points)
Maintaining a constant cellular environment requires complex metabolic regulation that coordinates
the use of nutrient pools
Hormones coordinate metabolic relations between different tissues, often by regulating the reversible modification of key enzymes
Metabolism is regulated through control of
-the amounts of enzymes
-their catalytic activities
-the accessibility of substrates.
Glucose-6-phosphate----- PPP
Pyruvate----WAG TCS
Acetyl CoA--- CAC, FA synthesis, Cholesterol synthesis, ketone bodies (acetoacetate- WYKLF)
3. Glutamate serves as the major source of amino groups in metabolism. Identify the
key enzyme in glutamate metabolism and write equations for the reactions they
catalyze. (15 points)
4. Give examples of two amino acids and show how they interact with the Krebs cycle.
What is the metabolic importance of the interaction? (20 points)
5. Glucose, glycerol, and fructose are all effective antiketogenic agents (i.e. they
decrease the level of circulating ketone bodies). Give a rationale as to how these
agents.J2,,,, <. .f::. '.. . (20 points)