Protein acetoacetylation

When both building block units are m place on the acyl carrier protein carbon-carbon bond formation occurs between the a carbon atom of the malonyl group and the carbonyl carbon of the acetyl group This is shown m step 1 of Figure 26 3 Carbon-carbon bond formation is accompanied by decarboxylation and produces a four carbon acetoacetyl (3 oxobutanoyl) group bound to acyl earner protein... 

The introduction to Section 26 8 pointed out that mevalonic acid is the biosynthetic pre cursor of isopentenyl pyrophosphate The early steps m the biosynthesis of mevalonate from three molecules of acetic acid are analogous to those m fatty acid biosynthesis (Sec tion 26 3) except that they do not involve acyl earner protein Thus the reaction of acetyl coenzyme A with malonyl coenzyme A yields a molecule of acetoacetyl coenzyme A... 

During periods of hunger, muscle proteins serve as an energy reserve for the body. They are broken down into amino acids, which are transported to the liver. In the liver, the carbon skeletons of the amino acids are converted into intermediates in the tricarboxylic acid cycle or into acetoacetyl-CoA (see p. 175). These amphibolic metabolites are then available to the energy metabolism and for gluconeogenesis. After prolonged starvation, the brain switches to using ketone bodies in order to save muscle protein (see p. 356). 

The following experiments shed some light. Kinetic studies of sucdnyl-CoA-acetoacetate CoA transferase indicate a ping-pong mechanism. The enzyme alternates between two distinct forms, one of which has been shown to contain bound CoA.932-934 The E-CoA intermediate formed from enzyme plus acetoacetyl-CoA was reduced with 3H-containing sodium borohydride and the protein was completely hydrolyzed with HC1. Tritium-containing a-amino-8-hydroxyvaleric acid was isolated. Since thioesters (as well as oxygen esters) are cleaved in a two-step process... 

Answer Lysine and leucine are exclusively ketogenic. These amino acids are degraded entirely to acetyl-CoA and acetoacetyl-CoA, and no parts of their carbon skeletons can be used for glucose synthesis. Leucine is especially common in proteins. Its degradation makes a substantial contribution to ketosis under starvation conditions. 

The catabolism of lysine merges with that of tryptophan at the level of (3-ketoadipic acid. Both metabolic pathways are identical from this point on and lead to the formation of acetoacetyl-CoA (Figure 20.21). Lysine is thus ketogenic. It does not transaminate in the classic way. Lysine is a precursor of carnitine the initial reaction involves the methylation of e-amino groups of protein-bound lysine with SAM. The N-methylated lysine is then released proteolytically and the reaction sequence to carnitine completed. See Equation (19.6) for the structure of carnitine. 

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