Catabolism of CoA

Phosphopemtetheine, tnisingfrom either the catahoUsm of CoA or the inactivation of holo-acyl carrier protein (ACP), can he reutilized for CoA synthesis. Phosphopantetheine is a potent inhihitor of ptmtothenic acid kinase, the first step of de novo CoA synthesis. 

Alternatively, phosphopantetheine is dephosphorylated, again hy a relatively unspecific phosphatase. The resultemt peuitetheine is cleaved by pante-theinase, a specific amidase, to pantothenic acid emd cysteamine. The resultant cysteamine may be an important precursor of taurine (Section 14.5.1). Pan-tetheinase is found in both the liver and kidneys. The kidney isoenzyme acts on both pemtetheine emd (at a lower rate) on phosphopantetheine, whereas the liver enzyme acts only on pantetheine (Dupre etal., 1973 Wittweretal., 1983). 

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The catabolism of amino acids provides pyruvate, acetyl-CoA, oxaloacetate, fumarate, a-ketoglutarate, and succinate, ail of which may be oxidized by the TCA cycle. In this way, proteins may serve as excellent sources of nutrient energy, as seen in Chapter 26. 

Look al the catabolism of my fistic acid shown in Figure 29.4 to see the overall results of the /3-oxidation pathway. The first passage converts the 14-carbon myristoyl CoA into the 12-carbon lauroyl CoA plus acetyl CoA, the second passage converts lauroyl CoA into the 10-carbon caproyl CoA plus acetyl CoA, the third passage converts caproyl CoA into the 8-carbon capryloyl CoA, and so on. Note that the final passage produces two molecules of acetyl CoA because the precursor has four carbons. 

Figure 29.4 Catabolism of the 14-carbon myristicacid by the 0-oxidation pathway yields seven molecules of acetyl CoA after six passages.

Problem 29.3 How many molecules of acetyl CoA are produced by catabolism of the following fatty acids, and how many passages of the )S-oxiclation pathway are needed ... 

How many moles of acetyl CoA are produced by catabolism of the follow-ing substances ... 

How many grams of acetyl CoA (MW = 809.6 amu) are produced by catabolism of the following substances Which substances is the most efficient precursor of acetyl CoA on a weight basis ... 

Figure 15-1. Outline of the pathways for the catabolism of dietary carbohydrate, protein, and fat. All the pathways lead to the production of acetyl-CoA, which is oxidized in the citric acid cycle, ultimately yielding ATP in the process of oxidative phosphorylation.

Threonine. Threonine is cleaved to acetaldehyde and glycine. Oxidation of acetaldehyde to acetate is followed by formation of acetyl-CoA (Figure 30-10). Catabolism of glycine is discussed above. 

Figure 30-20. Catabolism of the 3-methylcrotonyl-CoA formed from i-leuclne. Asterisks Indicate carbon atoms derived from CO2.

Figure 30-21. Subsequent catabolism of the tiglyl-CoA formed from L-isoleucine.

Figure 30-22. Subsequent catabolism of the methacrylyl-CoA formed from i-valine (see Figure 30-19). (a-KA, a-keto acid a-AA, a-amino acid.)...

Methylmalonyl CoA mutase, leucine aminomutase, and methionine synthase (Figure 45-14) are vitamin Bj2-dependent enzymes. Methylmalonyl CoA is formed as an intermediate in the catabolism of valine and by the carboxylation of propionyl CoA arising in the catabolism of isoleucine, cholesterol, and, rarely, fatty acids with an odd number of carbon atoms—or directly from propionate, a major product of microbial fer-... 

The catabolism of all 21 amino acids gives rise to only six common intermediates acetyl-CoA, pyruvate, oxoglutarate, succinyl-CoA, fumarate or oxaloacetate (Table 8.10). 

The intermediary metabolism has multienzyme complexes which, in a complex reaction, catalyze the oxidative decarboxylation of 2-oxoacids and the transfer to coenzyme A of the acyl residue produced. NAD" acts as the electron acceptor. In addition, thiamine diphosphate, lipoamide, and FAD are also involved in the reaction. The oxoacid dehydrogenases include a) the pyruvate dehydrogenase complex (PDH, pyruvate acetyl CoA), b) the 2-oxoglutarate dehydrogenase complex of the tricarboxylic acid cycle (ODH, 2-oxoglutarate succinyl CoA), and c) the branched chain dehydrogenase complex, which is involved in the catabolism of valine, leucine, and isoleucine (see p. 414). 

Mechanism of Action Inhibit HMG-CoA reductase, preventing the conversion of HMG-CoA to mevalonate, an early step in cholesterol biosynthesis Depletion of cellular cholesterol stimulates the production of cell surface receptors that recognize LDL, leading to increased catabolism of LDL cholesterol ... 

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