Bacteria threonine metabolism

Grimdy FJ, Lehman SC, HenMn TM (2003) The L box regtrlon lysine sensing by leader RNAs of bacterial lysine biosynthesis genes. Proc Natl Acad Sci USA 100 12057-12062 Hartman JLIV (2007) Buffering of deoxyribonucleotide pool homeostasis by threonine metabolism. Proc Natl Acad Sci USA 104(10) 11700-11705 Henkin TM, Yanofsky C (2002) Regirlation by transcription attenuation in bacteria how RNA provides instructions for transcription termination/antitermination decisions. Bioessays 24 700-707... 

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. 

Probably the most common and widespread control mechanisms in cells are allosteric inhibition and allosteric activation. These mechanisms are incorporated into metabolic pathways in many ways, the most frequent being feedback inhibition. This occurs when an end product of a metabolic sequence accumulates and turns off one or more enzymes needed for its own formation. It is often the first enzyme unique to the specific biosynthetic pathway for the product that is inhibited. When a cell makes two or more isoenzymes, only one of them may be inhibited by a particular product. For example, in Fig. 11-1 product P inhibits just one of the two isoenzymes that catalyzes conversion of A to B the other is controlled by an enzyme modification reaction. In bacteria such as E. coli, three isoenzymes, which are labeled I, II, and III in Fig. 11-3, convert aspartate to (3-aspartyl phosphate, the precursor to the end products threonine, isoleucine, methionine, and lysine. Each product inhibits only one of the isoenzymes as shown in the figure. 

Fig. 1.8 Asaccharolytic fermentation produces ammonia and short-chain fatty acids. This group of fermentations by oral bacteria utilizes proteins, which are converted to peptides and amino acids. The free amino acids are then deaminated to ammonia in a reaction that converts nicotinamide adenine dinucleotide (NAD) to NADH. For example, alanine is converted to pyruvate and ammonia. The pyruvate is reduced to lactate, and ammonium lactate is excreted into the environment. Unlike lactate from glucose, ammonium lactate is a neutral salt. The common end products in from plaque are ammonium acetate, ammonium propionate, and ammonium butyrate, ammonium salts of short chain fatty acids. For example, glycine is reduced to acetate and ammonia. Cysteine is reduced to propionate, hydrogen sulfide, and ammonia alanine to propionate, water, and ammonia and aspartate to propionate, carbon dioxide, and ammonia. Threonine is reduced to butyrate, water, and ammonia and glutamate is reduced to butyrate, carbon dioxide, and ammonia. Other amino acids are involved in more complicated metabolic reactions that give rise to these short-chain amino acids, sometimes with succinate, another common end product in plaque.

The oxidation of threonine, valine, methionine, and isoleucine results in propionyl-CoA, which propionyl-CoA carboxylase converts into L-methylmalonyl-CoA, which is metabolized through methylmalonyl-CoA mutase to succinyl-CoA. Whereas the breakdown of the above amino acids is felt to contribute to -50 % of the propiony 1-CoA production, gut bacteria and the breakdown of odd-chain-length fatty acids also substantially contribute to propionyl-CoA production (-25 % each), with a minimal contribution by cholesterol metabolism [10-13] (Fig. 17.1). 

This chapter will focus on the global metabolic pathway of L-threonine together with regulation mechanisms and the progress in metabolic engineering of the dominating industrial bacteria, E. coli and C. glutamicum. 

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