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Chemical Compound Review:

Thr-Met (2S)-2-[[(2R,3R)-2-amino-3- hydroxy...

Synonyms: AC1O532A

Pratta, M.A. et al., Yamamoto, H. et al., Krupa, R. et al., Mavromichalis, I. et al., Guinard, J. et al., et al.

Hu, Smith, Miller, Lohman, Case,

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Disease relevance of Thr-Met

For T439M, the Thr/Met genotype [odds ratio (OR) = 2.03, 95% confidence interval (CI) 1.04-3.98] and Thr/Met and Met/Met genotypes combined (OR = 2.37, 95% CI 1.23-4.56) demonstrated significant association with the development of colorectal cancer after adjusting for age, gender and smoking status [1].

High impact information on Thr-Met

The prevalence of the Thr/Met genotype (T/M) in all patients was not significantly different from that in the control group [2].
Mutation of residues 423 (Met/Ile), 444 (Thr/Met), and 506 (Asn/Ser) confer cholesteryl esterase activity on rat lung carboxylesterase. Ser-506 is required for activation by cAMP-dependent protein kinase [3].
Comparatively low eTS did not affect phenotype or Thr/Met level, however after Hser treatment HserP and Met accumulation were reduced compared with wild type and Thr was increased slightly [4].
The high-resolution X-ray structures have been determined for ten complexes formed between bovine beta-trypsin and P1 variants (Gly, Asp, Glu, Gln, Thr, Met, Lys, His, Phe, Trp) of bovine pancreatic trypsin inhibitor (BPTI) [5].
The Met/Met genotype was associated with a marked increase of 1.5 log units in the lipolytic sensitivity to the beta2-adrenoceptor agonist terbutaline (P=0.0008) as compared with the Thr/Thr and Thr/Met genotypes [6].

Biological context of Thr-Met

XRCC3-241Met homozygotes had an average DNA adduct level of 11.44 +/- 1.48 (+/-SE) compared with 7.69 +/- 0.88 in Thr/Met heterozygotes and 6.94 +/- 1.11 in Thr/Thr homozygotes (F = 3.206, P = 0.042) [7].
The cleavability of the chymotrypsin and elastase pa-mutants is most likely determined by replacement of Arg-1 by neutral amino acids such as Ile, Thr, Met or Leu, depending on the substrate specificity of the activating proteases [8].

Anatomical context of Thr-Met

Some essential AA (Lys, Arg, and branched-chain AA) were therefore taken up in excess of their output into milk proteins, but others (His, Thr, Met, and Phe) were almost exclusively extracted by the udder in a direct ratio to their output [9].

Associations of Thr-Met with other chemical compounds

PCR-restriction fragment length polymorphism (RFLP) assays were used to determine four genotypes of three DNA repair genes: XRCC1, 194 Arg/Trp and 399 Arg/Gln; XRCC3, 241 Thr/Met; and APE1, 148 Asp/Glu [10].

Gene context of Thr-Met

Cancer occurrence was strongly associated with the XRCC3 Met/Met polymorphic variant (OR = 9.45; (95% CI 8.77-11.65)), whereas Thr/Thr and Thr/Met variants were associated with significant reduction in colorectal cancer risk (OR = 0.16; 95% CI 0-0.26 and OR = 0.26; 95% CI 0.25-0.27, respectively) [11].
A new alpha 1-antitrypsin mutation, Thr-Met 85, (PI Zbristol) associated with novel electrophoretic properties [12].
Addition of Thr-Asn to the N-terminus (DP516) or substitution of the first two residues (Ala-Pro) of mature, native IL-1 beta with Thr-Met (DuP118) had no effect on the potency of the muteins in stimulating proteoglycan breakdown and inhibiting proteoglycan synthesis in vitro, or inducing mouse paw swelling in vivo [13].

Analytical, diagnostic and therapeutic context of Thr-Met

In Exp. 1, the addition of an amino acid mixture containing Lys, Trp, Thr, Met, Ile, and Val to the low-protein diet increased (P<.05) gain and gain: feed ratio, and these response traits were not different from those of pigs fed the 19.2% CP positive-control diet [14].

References

Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal cancer in a Japanese population. Yamamoto, H., Hanafusa, H., Ouchida, M., Yano, M., Suzuki, H., Murakami, M., Aoe, M., Shimizu, N., Nakachi, K., Shimizu, K. Carcinogenesis (2005) [Pubmed]
Coronary artery disease and polymorphisms in a receptor mediating shear stress-dependent platelet activation. Murata, M., Matsubara, Y., Kawano, K., Zama, T., Aoki, N., Yoshino, H., Watanabe, G., Ishikawa, K., Ikeda, Y. Circulation (1997) [Pubmed]
Mutation of residues 423 (Met/Ile), 444 (Thr/Met), and 506 (Asn/Ser) confer cholesteryl esterase activity on rat lung carboxylesterase. Ser-506 is required for activation by cAMP-dependent protein kinase. Wallace, T.J., Kodsi, E.M., Langston, T.B., Gergis, M.R., Grogan, W.M. J. Biol. Chem. (2001) [Pubmed]
Methionine and threonine synthesis are limited by homoserine availability and not the activity of homoserine kinase in Arabidopsis thaliana. Lee, M., Martin, M.N., Hudson, A.O., Lee, J., Muhitch, M.J., Leustek, T. Plant J. (2005) [Pubmed]
The crystal structures of the complexes between bovine beta-trypsin and ten P1 variants of BPTI. Helland, R., Otlewski, J., Sundheim, O., Dadlez, M., Smalås, A.O. J. Mol. Biol. (1999) [Pubmed]
Polymorphism of the AHSG gene is associated with increased adipocyte beta2-adrenoceptor function. Lavebratt, C., Dungner, E., Hoffstedt, J. J. Lipid Res. (2005) [Pubmed]
XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Matullo, G., Palli, D., Peluso, M., Guarrera, S., Carturan, S., Celentano, E., Krogh, V., Munnia, A., Tumino, R., Polidoro, S., Piazza, A., Vineis, P. Carcinogenesis (2001) [Pubmed]
Trypsin-resistant protease activation mutants of an influenza virus. Orlich, M., Linder, D., Rott, R. J. Gen. Virol. (1995) [Pubmed]
Effect of graded levels of duodenal infusions of casein on mammary uptake in lactating cows. 2. Individual amino acids. Guinard, J., Rulquin, H. J. Dairy Sci. (1994) [Pubmed]
Genetic regulation of ionizing radiation sensitivity and breast cancer risk. Hu, J.J., Smith, T.R., Miller, M.S., Lohman, K., Case, L.D. Environ. Mol. Mutagen. (2002) [Pubmed]
An association of polymorphism of DNA repair genes XRCC1 and XRCC3 with colorectal cancer. Krupa, R., Blasiak, J. J. Exp. Clin. Cancer Res. (2004) [Pubmed]
A new alpha 1-antitrypsin mutation, Thr-Met 85, (PI Zbristol) associated with novel electrophoretic properties. Lovegrove, J.U., Jeremiah, S., Gillett, G.T., Temple, I.K., Povey, S., Whitehouse, D.B. Ann. Hum. Genet. (1997) [Pubmed]
Effects of IL-1 muteins on cartilage degradation and as inducers of acute inflammation. Pratta, M.A., Arner, E.C., Rule, B.L., Galbraith, W. Agents Actions (1991) [Pubmed]
Limiting order of amino acids in a low-protein corn-soybean meal-whey-based diet for nursery pigs. Mavromichalis, I., Webel, D.M., Emmert, J.L., Moser, R.L., Baker, D.H. J. Anim. Sci. (1998) [Pubmed]

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