Serine catabolic pathways

There are several catabolic pathways for serine (Appendix 8.3). 

Figure 20.15 Interrelationships between the serine and glycine metabolic pathways. FH4-"C" indicates 5,10-methylenetetrahydrofolate. (Adapted from Yoshida T, Kikuchi G. Comparative study on major pathways of glycine and serine catabolism in vertebrate livers. ) Biochem 72 1503-1516, 1972.)...

Ammonium ions are produced by the catabolism of a number of amino acids. Glutamate dehydrogenase is the major source of ammonium ions in the body. Ammonium ions are also produced from the catabolic pathways of serine, histidine, tryptophan, glycine, glutamine, and asparagine. L-Amino acid oxidase and... 

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

The concept of sparing of one nutrient by another was introduced earlier, where it was demonstrated that dietary carbohydrate can spare protein. Similarly, cysteine can spare methionine and tyrosine can spare phenylalanine. A certain proportion of dietary methionine is converted to cysteine. Mediionine normally supplies part of the body s needs for cysteine. With cysteine-free diets, methionine can supply all of the body s needs for cysteine. The methionine catabolic pathway that leads to cysteine production is shown in Figure 8.27. Only the sulfur atom of methionine appears in the molecule of cysteine serine supplies the carbon skeleton of cysteine. a-Ketobutyrate is a byproduct of the pathway. a-Ketobutyrate is further degraded to propionyl-CoA by BCKA dehydrogenase or pyruvate dehydrogenase. Propionyl-CoA is then converted to succinyl-CoA, an intermediate of the Krebs cycle. 

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

The major pathway of serine catabolism probably is by way of its enzymatic dehydration and subsequent spontaneous deamination to yield pyruvic acid (see Fig. 2). An evidence for this is the observation of Lien and Greenberg that alanine is the major amino acid formed from serine-3-C by liver mitochondrial preparations. The alanine could be fomed from the pyruvic acid by transamination. 

Serine, like alanine, is converted into pyruvate by a PLP-dependent pathway, but the two reaction sequences are not the same. Whereas alanine catabolism involves a PLP-dependent transamination, serine catabolism involves a PLP-dependent dehydration to form an intermediate enamine that is then hydrolyzed. 

Fia. 1. Glycine catabolism pathway 1, via serine and pyruvate pathway 2, via glyoxylic acid and formate pathway 3, via the glycine-succinate cycle. 

In addition to its conversion to glycine, shown in Fig. 1, other possible pathways of serine catabolism are represented in Fig. 2. 

A number of investigators have attempted to determine the major pathways of serine catabolism from distribution of the C Mabel of isotopic serine in glycogen and other amino acids in the intact rat (47, 4S) and in a variety of products in rat liver slices (49). The results indicated that the metabolic pathways of L-serine and D-serine are quite distinct. In other respects there is no general agreement. Koeppe and co-workers (47, 4S) determined that conversion to pyruvate is an important pathway of L-serine degradation, while an important product of unknown nature is formed as an intermediate from D-serine. Elwyn et al. (49) concluded that conversion to glycine is probably the major pathway for L-serine metabolism. 

More recently, Pearce and Heydeman suggested non-oxidative removal of ethylene glycol units as acetaldehyde by a membrane-bound, oxygen-sensitive enzyme of a novel type, i.e., diethylene glycol lyase (18). Schoberl suggested that PEG was catabolized by Ci step, liberating formate which was metabolized by a serine pathway (19). 

Figure 2. Aerobic catabolism of methylated sulfides (adapted from Kelly, 1988). 1) DMSO reductase (Hyphomicrobium sp.) 2) DMDS reductase (Thiobacillus sp. 3) trimethylsulfonium-tetrahydrofolate methyltransferase (Pseudomonas sp.) 4) DMS monooxygenase 5) methanethiol oxidase 6) sulfide oxidizing enzymes 7) catalase 8) formaldehyde dehydrogenase 9) formate dehydrogenase 10) Calvin cycle for CO2 assimilation (Thiobacillus sp.) 11) serine pathway for carbon assimilation (Hyphomicrobium sp.).

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. 

FIGURE a.27 Pathway for methionine cataboLsm and cysteine synthesis. Methionine is the source of the sulfur atom of cysteine. Serine is the source of the carbon skeleton of serine. In methionine catabolism, the carbon skeleton of methionine is converted to propionyl-CoA, which eventually enters the Krebs cycle at the point of succinyl-CoA. BCAA dehydrogenase catalyzes the oxidation of a ketobutyrate to propionyXloA-... 

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-... 

There are three known pathways for the catabolism of serine, pyruvate + H2O... 

The third catabolic route would be by the conversion of the 1 and 2 carbon atoms of serine to glycine with the concomitant producticm of methylene THF from C-3 (reaction 5). The enzyme catalyzing this reaction is serine hydroxymethyltransferase (E.C. 2.1.2.1). It has been found in a number of higher plants and partially purified from tobacco root (Prather and Sisler, 1966) and cauliflower bud (Mazelis and Liu, 1967). The glycine formed can then be degraded by the pathways described above (Section 1I,E). The methylene-THF can be oxidized to the Ai-formyl THF and then to CO2 and THF. This latter reaction has been reported in pea mitochondria by Clandinin and Cossins (1975). 

This leads us to another pathway for the catabolism of glycine which must be of very great significance. This is the conversion of glycine to serine (reaction 4). The subsequent fate becomes that of serine, which is discussed in the next section. 

---