Question

5

pt

homework

–

due 11/20

Draw how the glycolytic and CAC pathways

connect, their cellular locations and regulation

of the pathways. Include enzyme and

substrate/product names

Answer 1

Entry into the citric acid cycle is largely controlled through pyruvate dehydrogenase (above), the enzyme that produces acetyl CoA. However, there are two additional steps in the cycle that are subject to regulation. These are the two steps in which carbon dioxide molecules are released, and also the steps at which the first two NADH molecules of the cycle are produced.

Isocitrate dehydrogenase controls the first of these two steps, turning a six-carbon molecule into a five-carbon molecule. This enzyme is inhibited by ATP and NADH but activated by ADP.

α-Ketoglutarate dehydrogenase controls the second of these two steps, turning the five-carbon compound from the previous step into a four-carbon compound bound to CoA (succinyl CoA). This enzyme is inhibited by ATP, NADH, and several other molecules, including succinyl CoA itself.

Acetyl CoA regulator activates Enzyme H requlator inhibits enzyme Isocitvate ATP, NADH ADP I3OCITRATE DEHYDROGENASE -ketogutarale - KETOGLUTARATE ATP, NAD, Succinyl CoA DEHYDROGENASE Suociny CoA

Diagram showing regulation of the citric acid cycle. The conversion of isocitrate to α-ketoglutarate is catalyzed by the enzyme isocitrate dehydrogenase, while the conversion of α-ketoglutarate to succinyl CoA is catalyzed by the enzyme α-ketoglutarate dehydrogenase.

Isocitrate dehydrogenase is inhibited by ATP and NADH and positively regulated by ADP.

α-Ketoglutarate dehydrogenase is inhibited by ATP, NADH, and succinyl CoA.

Putting it all together:

There are lots of other regulatory mechanisms for cellular respiration besides the ones we've discussed here. For instance, the speed of the electron transport chain is regulated by levels of ADP and ATP, and many other enzymes are subject to regulation. However, these examples give you a feel for the kind of logic and strategies cells use to regulate metabolic processes.

At each stage, we can see similar elements. For instance, we see feedback inhibition at many stages, at the level of pathways and of individual reactions. Monitoring of the cell's energy state through levels of molecules like ATP, ADP, AMP, and NADH is another common feature.

The diagram below summarizes the key enzymes we’ve discussed, along with some of their most important regulators.

Glucose ATP, Citrate AMP VFuctose.6-phosphate PHOSPHOFRUCTO KINASE (PFK) = regulator activates enzyme regulator inhibts enzyme Fructose-l,o b1sphosphate Pyruvate Acetyl CoA PYRUVATE DEHYDROGENASE ATP, acetyl CoA, NADH ADP, Pynavate Isocilvae FATP, NADH ADP ISOCITRATE DEHYDROGENASE AOP d-ketooutaral - KETOGLUTARATE ATP, NADH, Succinyl CoA DEHYDROGENASE Succiny CoA T