Malonate is an analog of succinate, which is a natural substrate for the Krebs c
ID: 95922 • Letter: M
Question
Malonate is an analog of succinate, which is a natural substrate for the Krebs cycle. Malonate inhibits succinate dehydrogenase, the enzyme that catalyzes the conversion of succinate to fumarate (which occurs during step 6 the second phase of the Krebs cycle). Now, consider the following experimental scenario that involves malonate: You add mitochondria and malonate to your reaction flask. You allow the reaction to proceed for one minute, then add succinate. What would happen to oxygen consumption in this experiment, then What would happen if add pyruvate? What would happen to oxygen consumption if you were to perform similar independent experiments by adding malate, fumarate, and ADP, to mitochondria containing malonate? Finally, Discuss the sequence of steps involving succinate, pyruvate, malate and fumarate relative to where malonate is acting. If needed, consult the diagrams in your lecture course textbook. What would happen to the concentration of each of the following molecules: citrate, isocitrate, a-ketoglutarate, succinate, oxaloacetate, malonate, ADP, and ATP in your hypothetical experiment if you treated mitochondria with excess amounts of malonate?
Explanation / Answer
The citric acid chain is a complex array of a chemical reaction. It converts the acetyl co-A to various biochemical compounds and finally produces the reduced molecules to generate ATP via ETC. The reaction has several steps each catalysed by the separate enzyme. The reduced molecules once enter the ETC, consume oxygen to produce ATP.
The compound malonate blocks the conversion of succinate to fumarate by blocking the enzyme succinate dehydrogenase. When the mitochondria and malonate are added in the reaction mix, the dehydrogenase enzyme is inhibited. The succinate added after a minute, will not be converted to fumarate.Since the reaction will not complete, the oxygen consumption decreases. When the pyruvate is added, the reaction is pushed forward.But since the cycle is incomplete due to the presence of malonate, the oxygen consumption will remain unchanged as earlier.
The presence of malate, fumarate and ADP, would bypass the conversion of succinate to fumarate. Hence the oxygen consumption will increase. The ADP is also an inducer to produce more of ATP.
The succinate is converted to fumarate and this reaction is inhibited by the malonate. The pyruvate acts as an inducer of the TCA cycle, and again the reaction proceeds and stops at succinate. The malate and fumarate occur after the succinate, hence the presence of malonate cannot stop the conversion of malate and fumarate to oxaloacetate and production of NADH.
If the mitochondria and excess malonate are mixed, the succinate would accumulate in the reaction mix. CItrate, isocitrate, ketoglutarate, will all reduce . the oxaloacetate also will be reduced. ADP would increase and ATP would decrease.
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