Amino acid metabolism threonine

Sterol biosynthesis Bile acid biosynthesis C2rSteroid hormone metabolism Androgen and estrogen metabolism Nucleotide Metabolism Purine metabolism Pyrimidine metabolism Nucleotide sugar metabolism Amino sugar metabolism Amino Acid Metabolism Glutamate metabolism Alanine and aspartate metabolism Glycine, serine, and threonine metabolism... 

A subclass of lyases, involved in /J-hydroxy-a-amino acid metabolism, utilizes pyridoxal 5 -phosphate (PLP) as a prosthetic group for imine/enamine type activation. These enzymes are not only of interest for the synthesis of the naturally occurring prototypes L-serine (Sect. 6.8) or L-threonine, but also offer a potential entry to rare or non-natural analogs. 

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. 

See also Citric Acid Cycle Intermediates in Amino Acid Metabolism, Metabolism of Serine, Glycine, and Threonine, Metabolism of Valine, Leucine, Isoleucine, and Lysine, Metabolism of Sulfur-Containing Amino Acids... 

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

Figure 9-3. Fates of the carbon skeletons upon metabolism of the amino acids. Points of entry at various steps of the tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis are shown for the carbons skeletons of the amino acids. Note the multiple fates of the glucogenic amino acids glycine (Gly), serine (Ser), and threonine (Thr) as well as the combined glucogenic and ketogenic amino acids phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). Ala, alanine Cys, cysteine lie, isoleucine Leu, leucine Lys, lysine Asn, asparagine Asp, aspartate Arg, arginine His, histidine Glu, glutamate Gin, glutamine Pro, proline Val, valine Met, methionine.

The formation of succinyl coenzyme A from methylmalonyl coenzyme A, part of the metabolism of odd-chain fatty acids, cholesterol, and the amino acids valine, isoleucine, threonine, and methionine... 

Cyclosporins, produced by the filamentous fungus Tolypocladium niveum and by numerous strains of Fusaria and Neocosmospora, are a class of cyclic undecapep-tides which are composed of hydrophobic aliphatic amino acids [73-75], They exhibit antiinflammatory, immunosuppressive, antifungal, and antiparasitic properties [74], The main metabolite, cyclosporin A, is in clinical use worldwide under the trade name SANDIMMUN to prevent allograft rejection [77,78], Besides cyclosporin A, there are 24 naturally occuring cyclosporins which have substitutions of amino acids in positions 1, 2, 4, 5, 7, and 11 and/or contain unmethylated peptide bonds in positions 1,4,6,9,10, or 11 [79-82], Cyclosporin A contains three nonproteinogenic amino acids D-alanine in position 8, L-a-aminobutyric acid in position 2, and, in position 1, the unusual amino acid 4(R)-4-[(E)-2-butenyl]-4-methyl-L-threonine (Bmt) (Fig. 8). All three amino acids have to be synthesized by a pathway independent of the primary metabolism. In addition, several peptide bonds of the cyclosporin molecule are A -mcthylated similar to the depsipeptides enniatin, beauvericin and PF1022A-related peptides. 

L-Threonine is one of the three major amino acids produced by fermentation processes [45]. Currently, more than 4,000 tons of L-threonine are produced annually by fermentation [46]. In this section, we examine the L-threonine biosynthetic pathway and its regulation, and discuss how the carbon flux can be maximized towards L-threonine biosynthesis by metabolic engineering. The detailed description on L-threonine biosynthetic pathways and regulations involved is shown in Fig. 1. 

Fig. 2 Metabolic pathways in C. glutamicum for biosynthesis of the aromatic amino acids tryptophan, tyrosine, and phenylalanine (a) and amino acids belonging to the aspartate family including lysine, methionine, threonine, and isoleucine (b). Metabolic regulation by feedback inhibition is indicated by dotted lines...

Pyridoxal 5 -phosphate is an essential cofactor for many enzymes responsible for the metabolic conversions of amino acids. The fourth step in its synthetic pathway in Escherichia coli is catalyzed by the divalent metal ion-dependent enzyme 4-hydroxythreonine-4-phosphate dehydrogenase (PdxA), which converts 4-hydroxy-l-threonine phosphate (HTP) to 3-amino-2-oxopropyl phosphate. The... 

Mutation. For industrial applications, mutations are induced by x-rays, uv irradiation or chemicals (nitrosoguanidine, EMS, MMS, etc). Mutant selections based on amino acid or nucleotide base analogue resistance or treatment with Nystatin or 2-deoxyglucose to select auxotrophs or temperature-sensitive mutations are easily carried out. Examples of useful mutants are strains of Candida membranefaciens, which produce L-threonine Hansenula anomala, which produces tryptophan or strains of Candida lipofytica that produce citric acid. An auxotrophic mutant of S. cerevisiae that requires leucine for growth has been produced for use in wine fermentations (see also Wine). This yeast produces only minimal quantities of isoamji alcohol, a fusel oil fraction derived from leucine by the Ehrlich reaction (10,11). A mutant strain of bakers yeast with cold-sensitive metabolism shows increased stability and has been marketed in Japan for use in doughs stored in the refrigerator (12). 

Most of the prokaryotic and many eukaryotic organisms (plants) are capable of synthesizing all the amino acids present in the protein. But higher animals including man possess this ability only for certain amino acids. The other amino acids, which are needed for normal functioning of the body but cannot be synthesized from metabolic intermediates, are called essential amino acids. These must be obtained from the diet and a deficiency in any one of the amino acids prevents growth and may even cause death. Methionine, Threonine, Tryptophan, Valine, Isoleucine, Leucine, Phenylalanine and Lysine are the essential amino acids, however, Histidine and Arginine are considered semi essential amino acids as it can be partly synthesized by the body. 

Propionyl-CoA is an intermediary product in the metabo-hsm of four essential amino acids (isoleucine, valine, threonine, and methionine), the aliphatic side-chain of cholesterol, pyrimidines (uracd and thymine), and the final product of the [3-oxidation of odd-chain fatty acids. Under normal circumstances, propionyl-CoA first is converted by a biotin-dependent carboxylase to methylmalonyi-CoA, then to succinyl-CoA by an adenosylcobalamin-dependent mutase, leading to oxidation in the tricarboxylic acid cycle. Primary or secondary defects of these two enzymes were among the first organic acidurias to be discovered, and their natural history has been characterized perhaps better than any other inborn error of organic acid metabolism. 

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