Serine carbon catabolism

Serine - Serine has many important biological roles, including the biosynthesis of phosphopholipids and cysteine. Serine also contributes activated one-carbon units to the pool of tetrahydrofolate coenzymes. Serine can be made in a variety of ways, including the way shown here and Figure 21.24. Serine is catabolized by conversion to glycine or by action of serine-threonine dehydratase (Figure 21.25). 

The carbon chain of cysteine and cystine is derived from serine by a mechanism discussed in the chapter, Metabolism of Sulfur-Containing Compounds. The sole source of tyrosine for the vertebrates is phenylalanine, as is explained in the chapter. Carbon Catabolism of Amino Acids. 

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

The carbon skeletons of six amino acids are converted in whole or in part to pyruvate. The pyruvate can then be converted to either acetyl-CoA (a ketone body precursor) or oxaloacetate (a precursor for gluconeogenesis). Thus amino acids catabolized to pyruvate are both ke-togenic and glucogenic. The six are alanine, tryptophan, cysteine, serine, glycine, and threonine (Fig. 18-19). Alanine yields pyruvate directly on transamination with... 

In the biosynthesis of serine from glycine, (25) serves as the methylene donor. The reverse of this reaction is important in the catabolism of serine and provides a major source of the one-carbon units needed in biosynthesis (80MI11003). In addition to tetrahydrofolate, pyridoxal phosphate is required as a coenzyme in this transformation. The topic will be taken up again in the next section. 

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.).

The carbon skeleton of methionine is converted to a-ketobutyrate (Figure 20.17), which is catabolized to propionyl-CoA and then to succinate. The sulfur atom is transferred to serine in the cystathionase reaction to yield cysteine. Cysteine is nonessential, because it can be derived from serine and methionine. 

The major point of entry for one-carbon fragments into substituted folates is methylene-tetrahydrofolate, which is formed by the catabolism of glycine, serine, and choline. 

Disposal of Surplus One-Carbon Fragments With the exception of serine hydroxymethyltransferase (Secdon 10.3.1.1), aU of the reactions shown in Figure 10.4 as sources of one-carbon subsdtuted folates are essentially catabolic reactions. When there is a greater entry of single carbon units into the folate pool than is required for biosynthetic reactions, the surplus can be oxidized to carbon dioxide byway of 10-formyl-tetrahydrofolate, thus ensuring the avaUabUity of tetrahydrofolate for catabolic reactions. 

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-... 

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. 

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-... 

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). 

In summary, the biochemical function of folate coenzymes is to transfer and use these one-carbon units in a variety of essential reactions (Figure 2), including de novo purine biosynthesis (formylation of glycinamide ribonucleotide and 5-amino-4-imidazole carboxamide ribonucleotide), pyrimidine nucleotide biosynthesis (methylation of deoxyuridylic acid to thy-midylic acid), amino-acid interconversions (the interconversion of serine to glycine, catabolism of histidine to glutamic acid, and conversion of homocysteine to methionine (which also requires vitamin B12)), and the generation and use of formate. 

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