Highlights Lipid Metabolism II

1. Fatty acids with odd numbers of carbons stop the breakdown process when they get to the three carbon propionyl-CoA molecule. To convert it further, a carboxyl group is added and the molecule is rearranged to succinyl-CoA. This step requires vitamin B12.

2. Ketone bodies are the body's means to provide energy to the brain when glucose concentrations are VERY low. This can occur during starvation or with some types of diabetes. Ketone bodies are made by putting together acetyl-CoAs to make four carbon intermediates by reversing the reaction catalyzed by thiolase. The four carbon molecules are converted to a six carbon molecule (called HMG-CoA) and it is broken back down to a four carbon molecule and acetyl-CoA. Ketone bodies are carried in the blood to the brain. One of these intermediates is chemically unstable and breaks down to acetone, which is exhaled from the lungs. Thus, the smell of acetone on a person's breath may be a sign of a serious problem.

3. Unsaturated fatty acids produced biologically are almost always in the cis configuration. By contrast, partial hydrogenation of vegetable oils (to raise the melting point) causes trans bond to be produced and thus trans fats are made. Trans fats are linked to atherosclerosis. The reason is not completely clear, but the random positioning of the trans bonds may be a factor.

4. Fatty acids are synthesized in the cytoplasm and each step increases the size of the fatty acid by two carbons. Acetyl groups are shuttled out of the mitochondria using citrate. Thus, most fatty acids have even numbers of carbons. Many of the steps of fatty acid synthesis are CHEMICALLY similar to the reversal of beta oxidation.

5. Fatty acids in the process of being synthesized are attached to a molecule called ACP (acyl carrier protein) instead of CoA. Fatty acid biosynthesis begins with formation of a three carbon molecule called malony-CoA. This comes about from addition of a carboxyl group (biotin is a required coenzyme). The enzyme responsible for this reaction is acetyl-CoA carboxylase (note that this enzyme is DIFFERENT from fatty acid synthase below). Acetyl-CoA carboxylase is the only regulated enzyme in fatty acid biosynthesis and is activated by citrate and inhibited by palmitate. Malonyl-CoA is readily converted to malonyl-ACP.

6. In the next step of fatty acid biosynthesis, two carbons of the malonyl-ACP are joined to the growing fatty acid and the carboxyl group that was added is lost as carbon dioxide.

7. The enzyme responsible for fatty acid synthesis has multiple catalytic activities and is known as Fatty Acid Synthase. It contains all of the catalytic activities necessary to make fatty acids up to 16 carbons in size. Synthesis of longer fatty acids requires other enzymes and occurs in the endoplasmic reticulum.