Threonine degradation

In the laboratory, serine hydroxymethyltransferase will catalyze the conversion of threonine to glycine and acetaldehyde in one step, but this is not a significant pathway for threonine degradation in mammals. 

There are two significant pathways for threonine degradation. One pathway leads to pyruvate via glycine (Fig. 18-19). The conversion to glycine occurs in two steps, with threonine first converted to 2-amino-3-... 

These amino acids are converted to succinyl-CoA isoleucine also contributes two of its carbon atoms to acetyl-CoA (see Fig. 18-21). The pathway of threonine degradation shown here occurs in humans a pathway found in other organisms is shown in Figure 18-19. 

Under physiological conditions, alcohol may be formed in intermediary metabolism as an intermediate product, e. g. in pyruvate decarboxylation and threonine degradation. Here minimal amounts of alcohol may arise (blood alcohol concentration of about 0.0009-... 

S. C. Bell and J. M. Turner, Bacterial catabolism of threonine. Threonine degradation initiated by L-threonine acetaldehyde-lyase (aldolase) in species of Pseudomonas, Bioctem. /., 166 209 (1977). 

The a-oxoamine synthases family is a small group of fold-type I enzymes that catalyze Claisen condensations between amino acids and acyl-CoA thioesters (Figure 16). Members of this family are (1) 8-amino-7-oxononanoate (AON) synthase (AONS), which catalyzes the first committed step in the biosynthesis of biotine, (2) 5-aminolevulinate synthase (ALAS), responsible for the condensation between glycine and succinyl-CoA, which yields aminolevulinate, the universal precursor of tetrapyrrolic compounds, (3) serine palmitoyltransferase (SPT), which catalyzes the first reaction in sphingolipids synthesis, and (4) 2-amino-3-ketobutyrate CoA ligase (KBL), involved in the threonine degradation pathway. With the exception of the reaction catalyzed by KLB, all condensation reactions involve a decarboxylase step. 

Glycine can be synthesized from serine and, to a minor extent, threonine. The major route from serine is by a reversible reaction that involves FH4 and pyridoxal phosphate (Fig. 39.6). Tettahydrofolate is a coenzyme that transfers one-carbon groups at different levels of oxidation. It is derived from the vitamin folate and is discussed in more detail in Chapter 40. The minor pathway for glycine production involves threonine degradation (this is an aldolase-like reaction because threonine contains a hydroxyl group located two carbons from the carbonyl group). 

As discussed previously, the major route of threonine degradation in humans is by threonine dehydratase (see section 111.D.2.). In a minor pathway, threonine degradation by threonine aldolase produces glycine and acetyl CoA in the liver. 

Many pyrroles arise mainly as products of the MaiUard reaction of carbohydrates and prohne. Unsubstituted pyrrole and some alkylsubstituted pyrroles also result from pyrolysis of other amino acids. For example, pyrrole appears in the pyrolysate of glycine, serine, threonine or prohne, 1-methylpyrrole arises from hydrox-yproline, and 2-methylpyrrole and 3-ethyl-4-methylpyrrole are products of serine and threonine degradation. In general, pyrroles... 

Whereas SHMT in vivo has a biosynthetic function, threonine aldolase catalyzes the degradation of threonine both l- and D-spedfic ThrA enzymes are known [16,192]. Typically, ThrA enzymes show complete enantiopreference for their natural a-D- or a-t-amino configuration but, with few exceptions, have only low specificity for the relative threo/erythro-configuration (e.g. (122)/(123)) [193]. Likewise, SHMT is highly selective for the L-configuration, but has poor threo/erythro selectivity [194]. For biocatalytic applications, the knovm SHMT, d- and t-ThrA show broad substrate tolerance for various acceptor aldehydes, notably induding aromatic aldehydes [193-196] however, a,P-unsaturated aldehydes are not accepted [197]. For preparative reactions, excess of (120) must compensate for the unfavorable equilibrium constant [34] to achieve economical yields. 

Removal of a-amino nitrogen by transamination (see Figure 28-3) is the first catabolic reaction of amino acids except in the case of proline, hydroxyproline, threonine, and lysine. The residual hydrocarbon skeleton is then degraded to amphibolic intermediates as outhned in Figure 30-1. 

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