Acetyl CoA.

A big step in understanding metabolic integration is to see the important crossroads in the pathways. We have discussed glucose-6-phosphate in this light. Glycolysis, gluconeogenesis, glycogen metabolism, and the pentose phosphate pathway all pass through glucose-6-phosphate. Depending on the type of tissue, its status under signaling, the cell's metabolome and energy charge, metabolic flux will be moving along these pathways through glucose-6-phosphate. It can get complicated. The MCAT does not seem to be too brutal about it, although you definitely want to remember that only liver or kidney cells are able to perform gluconeogenesis.

Another key crossroads is acetyl CoA, the product of glycolysis-PDC, fatty acid oxidation, and some of the amino acid degradation pathways. Acetyl CoA can proceed to the citric acid cycle, fatty acid synthesis, or ketone body synthesis. As the product of pyruvate dehydrogenase, acetyl CoA could proceed either to the citric acid cycle or to fatty acid synthesis but not, generally, ketone body synthesis. As the product of β-oxidation, acetyl CoA would proceed to the citric acid cycle or to ketone body synthesis but not fatty acid synthesis.

A key takeaway is that both glycolysis-PDC and β-oxidation feed the citric acid cycle.

A second takeaway is that, just as acetyl-CoA is the product of the breakdown of fatty acids, it's also the building block of fatty acids (The actual detailed enzymatic pathway of fatty acid synthesis is not required foreknowledge for the MCAT, but you want to know the basic shape of it). In fatty acid synthesis, the acetyl CoA actually still does combine with oxaloacetate to form citrate but instead of going on with the citric acid cycle, the citrate is routed to shuttle the two carbon units to the cytosol for fatty acid synthesis.

The third takeaway is to understand why acetyl CoA from glycolysis-PDC could make it to fatty acid synthesis but not the acetyl CoA from β-oxidation. It would make no sense for the acetyl CoA produced by fatty acid breakdown to then be turned around and used to build fatty acids. This would be what is known as a futile cycle. (Malonyl-CoA is an intermediate in fatty acid synthesis. This inhibits fatty acids from associating with carnitine for shuttling into the mitochondria for breakdown).

The fourth takeaway is to understand why the acetyl CoA from glycolysis-PDC would not be routed to ketone body synthesis as could happen with the acetyl CoA from β-oxidation. If a liver cell has enough glucose to feed the tissues of the body, it will just send the glucose. It would not be directing acetyl CoA towards ketone body synthesis. The state of ketosis is the fasted state not the fed state. In other words, it would make no sense for large amounts of acetyl CoA produced through glycolysis-PDC to be routing into ketone body synthesis. Glycolysis runs in the liver in the fed state, but the acetyl CoA goes to fatty acid synthesis. Where this doesn't apply, though, is in diabetes. In diabetes, the liver cell is not receiving the message that there's plenty of glucose. Either the pancreas isn't producing insulin (type I diabetes) or the liver is resistant to it (type II diabetes). The liver is acting as if the body is in the fasted state. It acts like the body is starving even though it's actually fed. In that case, acetyl-CoA from glycolysis-PDC does flow into ketone body synthesis, which can lead to diabetic keto-acidosis.