Threonine catabolic pathways

FIGURE 18-27 Catabolic pathways for methionine, isoleucine, threonine, and valine. 

Threonine can be broken down by tw o separate pathways. Serine dehydratase catalyzes the conv ersion of threonine to 2-ketobutyrate plus an ammonium ion 2-ketobutyrate is then converted by branched-chaln keto acid (BCKA) dehydrogenase to propionyl-CoA plus carbon dioxide. Propionyl-CoA catabolism is described later in this chapter. Threonine can also be broken down by a complex that has been suggested to be composed of threonine dehydrogerraseand acetoacetone synthase (Tressel ef al., 1986). Here, threonine catabolism results in the production of acetyl CoA plus glycure. 

Amino Add Catabolic Pathways Starting with Oxidation Catabolism of Serine, Threonine, and Histidine... 

The Catabolic Pathways of Threonine, Glycine, Serine, Cysteine, and Alanine. 

Three pathways of threonine catabolism have been found in heterotrophs. 

During the catabolism of fatty acids with an odd number of carbon atoms and the amino acids valine, isoleucine and threonine the resultant propionyl-CoA is converted to succinyl-CoA for oxidation in the TCA cycle. One of the enzymes in this pathway, methylmalonyl-CoA miitase, requires vitamin B12 as a cofactor in the conve sion of methylmalonyl-CoA to succinyl-CoA. The 5 -deoxyadenosine derivative of cobalamin is required for this reaction. 

Serine is one of the two hydroxyamino acids, the other being threonine. Serine has two major pathways of catabolism. The first, and apparently predominant, direction in many mammals is catalyzed by serine dehydratase, where water is removed between the alpha and beta carbons of serine. A rearrangement of the double bond forms an amino acid with spontaneous hydrolysis to form pyruvate and ammonia. Pyruvate then can be metabolized as discussed in previous chapters. This enzyme is primarily active in the liver, where the ammo-... 

L-Homoserine is found in many tissues as a intermediate in amino acid metabolism, including threonine, isoleucine, and methionine. Catabolism of aspartate to homoserine is shown here. The biosynthetic pathway from homoserine to methionine is shown in Figure 21.6. 

Valine, leucine, and isoleucine - The synthetic pathway from threonine and pyruvate to valine, leucine and isoleucine is outlined in Figure 21.26. The last four reactions in the biosynthesis of valine and isoleucine are catalyzed by the same four enzymes. Threonine dehydratase, which catalyzes the first step in conversion of threonine to isoleucine, is inhibited by isoleucine. Leucine, isoleucine, and valine are all catabolized via transamination followed by oxidative decarboxylation of the respective keto-acids (see here) and oxidation. The oxidation is similar to fatty acid oxidation, except for a debranching reaction for each intermediate. 

One of the pathways to propanoyl-CoA is from catabolism of the amino acid threonine (Chapter 12). Thus, threonine (threonine dehydratase, EC 4.3.1.19, cofactor pyridoxal phosphate) undergoes deamination to give 2-oxobutanoate (a-ketobutyrate) as shown below. Then, 2-oxobutanoate (a-ketobutyrate) undergoes decarboxylation (perhaps as shown in Scheme 11.30) with formation of propanoyl dihydro-lipoamide in a (cofactor) thiamine diphosphate mediated step. Finally, as in Scheme 11.31, propanoyl-CoA is formed. An alternative pathway uses aferrodoxin to effect the decarboxylation of 2-oxobutanoate (a-ketobutyrate) Ferredoxins are small proteins containing iron and sulfur atoms in iron-sulfur clusters. 

Propionic acid fermentation is not limited to propionibacteria it functions in vertebrates, in many species of arthropods, in some invertebrates imder anaerobic conditions (Halanker and Blomquist, 1989). In eukaryotes the propionic acid fermentation operates in reverse, providing a pathway for the catabolism of propionate formed via p-oxidation of odd-numbered fatty acids, by degradation of branched-chain amino acids (valine, isoleucine) and also produced from the carbon backbones of methionine, threonine, thymine and cholesterol (Rosenberg, 1983). The key reaction of propionic acid fermentation is the transformation of L-methylmalonyl-CoA(b) to succinyl-CoA, which requires coenzyme B12 (AdoCbl). In humans vitamin B deficit provokes a disease called pernicious anemia. 

Probable pathways for the catabolism of threonine are shown in Fig. 3. The enzymatic formation of glycine from threonine was first reported by Braunstein and Vilenkina. It has been confirmed by Meltzer and Sprinson and in the laboratories of the writer. - ... 

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