Activities of threonine

The final reaction in the biosynthesis of threonine involves a /8-y rearrangement and the loss of phosphate from O-phosphohomoserine (Fig. 2). Threonine synthases have been isolated from Lemna (Schnyder et al., 1975) radish, sugarbeet (Madison and Thompson, 1975), peas (Schnyder et al., 1975 Thoen et al., 1978b), and barley (Aames, 1978). None of these enzymes has been extensively characterized but a requirement for pyridoxyl-5 -phosphate was demonstrated after partial purification of the barley and pea enzymes. Unlike several other enzymes associated with threonine synthesis, the activity of threonine synthase was not stimulated by monovalent cations. However, all of the plant enzymes are strongly activated by 5-adeno-sylmethionine (Section III,B,5). 

The dual metabolic function of threonine as an essential component of protein and as a precursor of isoleucine (Fig. 4) can be considered to represent a branch point in metabolism. The extent to which threonine will contribute to isoleucine biosynthesis is dependent upon the activity of threonine dehydratase, an enzyme that is well known to be subject to feed back inhibition by isoleucine. Threonine dehydratases isolated from a number of plants appear to have similar regulatory properties (Kagan et al., 1969a Dougall, 1970 Sharma and Mazumder, 1970 Bleckmanef al., 1971 E. Lissik and J. Bryan, in preparation). Positive cooperativity is observed in the presence of isoleucine, but the Vniax not altered. Valine can partially antagonize the... 

The concentration of AdoMet is approximately 40 fiM in germinating pea seeds (Dodd and Cossins, 1968) and approximately 14-30 fiM in L. paucicostata (Table I and Fig. 5). These concentrations are within the range in which activity of threonine synthase is very sensitive to changes in AdoMet concentration (Madison and Thompson, 1976 Aarnes, 1978 Thoen et al., 1978). The concentration of AdoMet in L. paucicostata that had been grown in the presence of exogenous methionine (Fig. 5) was approximately 300 p,M. At this concentration, threonine synthase is almost maximally stimulated by AdoMet (Madison and Thompson, 1976 Thoen etal, 1978). 

Evidence has been presented that L-threonine dehydrase 8S1), but not L-serine dehydrase, is an inducible enzyme in mice and rats. The activity of threonine dehydrase in the livers of these animals is increased up to four times the normal value by the intraperitoneal injection of substrate. No change in serine dehydrase activity was observed. This is substantiating evidence that two separate enzymes are involved for the two substrates. Similar effects could be shown in liver perfusion studies. The inducible character of L-threonine dehydrase in E. colt 232) has been observed (see discussion below). 

Phosphohomoserine serves as a precursor of both threonine and methionine in higher plants, and regulation of its utilization in both branches of the pathway would be expected. This appears to occur, in part, by 5-adenosylmethio-nine activation of threonine synthase (5). Results obtained with partially purified Lemna threonine synthase (Giovanelli et al, 1984) indicate that the enzyme is essentially inactive in the absence of -adenosylmethionine, which cooperatively activates the enzyme at concentrations of less than 100 /iM. Conceptually, methionine could be synthesized and converted to S-adenosylmethionine prior to enzyme activation and the synthesis of threonine. Both orthophosphate and AMP inhibit Lemna threonine synthase in vitro, but the physiological significance of these effects is uncertain (Giovanelli et al, 1986). 

Phosphohomoserine is a substrate for both threonine synthase and cystathionine y-synthase. Thus, although threonine synthase is not involved in the synthesis of either methionine or phosphohomoserine the properties of this enzyme are relevant to methionine synthesis as it competes with cystathionine y-synthase for the same substrate. Moreover, as discussed in the ensuing section, the activity of threonine synthase and the synthesis of phosphohomoserine are regulated by products of the methionine biosynthetic pathway. 5-Aden-osylmethionine is an extremely potent positive effector of threonine synthase, virtually serving as an absolute requirement for enzyme activity (Aames, 1978 Giovanelli et a/., 1984 Madison and Thompson, 1976 Thoen eta/., 1978). In the presence of SAM, Giovanelli et al. (1984) found that threonine synthase had an extremely high affinity for phosphohomoserine (A = 2.2-6.9 nM). 

Quaternary salts of the substances represented by tliese formulae have been prepared by Kogl, Veldstra and van der Laan as well as of the next lower homologues, the substituted butyraldehydes, and the methyl ethers of both series. Their pharmacological activities were negligible in comparison with that of muscarine, but as six stereoisomeric forms may be produced in each synthesis, the inactivity may be due to stereoisomerism, just as in the case of threonine (a-amino-)3-hydroxy-butyric acid) where West and Carter found that only the d —) form is... 

These enzymes are activated by the binding of cAMP or cGMP. When activated, cAKs and cGKs phosphorylate specific serine or threonine residues in target proteins control the activity of these proteins. 

G-protein-coupled receptor kinases (GRKs) are a family of enzymes that catalyze the phosphorylation of threonine or serine residues on G-protein-coupled receptors. Characteristically, GRKs only phosphorylate the ligand-activated form of the receptors. Phosphorylation by GRKs usually leads to impaired receptor/G-protein coupling. 

Sirolimus (SRL), also termed rapamycin is a macrolide lactone isolated from the ascomycete species Stre-ptomyces hygroscopicus. After binding to its cytosolic receptor FKBP-12 the resulting complex inhibits the multifunctional serine-threonine kinase mTOR (mammalian target of rapamycin). Inhibition of mTOR prevents activation of the p70S6 kinase and successive... 

MAPK cascades are composed of three cytoplasmic kinases, the MAPKKK, MAPKK, and MAPK, that are regulated by phosphorylation (Fig. 1) [1, 2]. The MAPKKK, also called MEKK for MEK kinase, is a serine/threonine kinase. Selective activation of MAPKKKs by upstream cellular stimuli results in the phosphorylation of MAPKK, also called MEK for MAP/ERK kinase by the MAPKKK. MAPKKK members are structurally diverse and are differentially regulated by specific upstream stimuli. The MAPKK is phosphorylated by the MAPKKK on two specific serine/ threonine residues in its activation loop. The MAPKK family members are dual specificity kinases capable of phosphorylating critical threonine and tyrosine residues in the activation loop of the MAPKs. MAPKKs have the fewest members in the MAPK signaling module. MAPKs are a family of serine/threonine kinases that upon activation by their respective MAPKKs, are capable of phosphorylating cytoplasmic substrates as well as... 

Peptidases have been classified by the MEROPS system since 1993 [2], which has been available viatheMEROPS database since 1996 [3]. The classification is based on sequence and structural similarities. Because peptidases are often multidomain proteins, only the domain directly involved in catalysis, and which beais the active site residues, is used in comparisons. This domain is known as the peptidase unit. Peptidases with statistically significant peptidase unit sequence similarities are included in the same family. To date 186 families of peptidase have been detected. Examples from 86 of these families are known in humans. A family is named from a letter representing the catalytic type ( A for aspartic, G for glutamic, M for metallo, C for cysteine, S for serine and T for threonine) plus a number. Examples of family names are shown in Table 1. There are 53 families of metallopeptidases (24 in human), 14 of aspartic peptidases (three of which are found in human), 62 of cysteine peptidases (19 in human), 42 of serine peptidases (17 in human), four of threonine peptidases (three in human), one of ghitamicpeptidases and nine families for which the catalytic type is unknown (one in human). It should be noted that within a family not all of the members will be peptidases. Usually non-peptidase homologues are a minority and can be easily detected because not all of the active site residues are conserved. 

Misra R, Srivastava N, Misra UK, et al. 1980. Effect of endosulphan on aniline hydroxylase activity of hepatic SER in rats fed lysine, threonine deficient and supplemented rice diets. Nutrition Reports International 21 425-428. 

This intermediate MAPK activator (MAPK kinase, MAPKK) is a 45 kDa phosphoprotein capable of phosphorylating MAPK on serine/threonine and tyrosine residues (Matsuda et al., 1992 Nakielny et al., 1992a Kosako et al., 1993). Like MAPK, the activity of MAPKK is regulated by phosphorylation. During oocyte maturation MAPKK is phosphorylated on threonine residues (Kosako et al., 1992), and this phosphorylation is required for its activity (Ahn et al., 1991 Gomez and Cohen, 1991 Kosako et al., 1992 Matsuda et al., 1992). MPF can activate both MAPKK and MAPK in vitro, with the activation of MAPK lagging behind that of MAPKK however, MPF cannot activate either purified MAPKK or MAPK that has been dephosphorylated by phosphatases (Matsuda et al., 1992). MAPKK and MAPK are therefore believed to function downstream of MPF (Fig. 3). 

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