This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Degradation/Utilization/Assimilation → Amines and Polyamines Degradation → Glycine Betaine Degradation|
Some taxa known to possess this pathway include : Aphanothece halophytica, Arthrobacter, Corynebacterium sp., Pseudomonas aeruginosa, Pseudomonas putida, Rattus norvegicus, Sinorhizobium meliloti Rm2011
Glycine betaine (N,N,N-trimethylglycine) is a very efficient osmolyte found in a wide range of bacteria and plants, where it is accumulated at high cytoplasmic concentrations in response to osmotic stress, to act as an osmoprotectant [Osteras98].
The degradation of glycine betaine, as well as its potential precursor, choline, have been proposed to exist as a mechanism for osmoregulation in Sinorhizobium meliloti and other organisms. When the bacteria grow at inhibitory osmolarity the enzyme activities that lead to glycine betaine degradation decrease, while the enzyme activities that convert choline to glycine betaine either remain constant or increase. In this way, a high concentration of glycine betaine can be maintained in osmotically stressed cells [Bernard86, Smith88a].
The degradation of glycine betaine proceeds by sequential demethylation [Bernard86, Smith88a]. The first methyl group is removed by glycine betaine transmethylase, producing N,N-dimethylglycine (DMG). The second methyl group is removed by the enzyme dimethylglycine dehydrogenase, forming N-methylglycine, or sarcosine, and the third methyl is removed by sarcosine oxidase (or in some organisms, monomethylglycine dehydrogenase), producing glycine and formaldehyde.
Sarcosine oxidase is a complex enzyme, containing four cofactors, one of which is tetrahydrofolate (THF). In the presence of THF the enzyme does not produce formaldehyde, but instead transfers the single carbon unit to THF, resulting in glycine and methylenetetrahydrofolate. Glycine and methylenetetrahydrofolate are the substrates of the enzyme serine hydroxymethyltransferase, which removes the single carbon unit from methylenetetrahydrofolate and transfers it to glycine, producing L-serine. Since at least in some cases the gene encoding the serine hydroxymethyltransferase is adjacent to the genes encoding the sarcosine oxidase subunits, it is very likely that L-serine is indeed the final product of this degradation pathway [Wagner97]. Much work has been done with sarcosine oxidase from Corynebacterium sp. P-1 [Chlumsky93, Chlumsky95, Willie96, Eschenbrenner01], but similar enzymes from other organisms have also been characterized [Meskys01].
Chlumsky93: Chlumsky LJ, Zhang L, Ramsey AJ, Jorns MS (1993). "Preparation and properties of recombinant corynebacterial sarcosine oxidase: evidence for posttranslational modification during turnover with sarcosine." Biochemistry 32(41);11132-42. PMID: 7692961
Chlumsky95: Chlumsky LJ, Zhang L, Jorns MS (1995). "Sequence analysis of sarcosine oxidase and nearby genes reveals homologies with key enzymes of folate one-carbon metabolism." J Biol Chem 270(31);18252-9. PMID: 7543100
Eschenbrenner01: Eschenbrenner M, Chlumsky LJ, Khanna P, Strasser F, Jorns MS (2001). "Organization of the multiple coenzymes and subunits and role of the covalent flavin link in the complex heterotetrameric sarcosine oxidase." Biochemistry 40(18);5352-67. PMID: 11330998
Lisa83: Lisa TA, Garrido MN, Domenech CE (1983). "Induction of acid phosphatase and cholinesterase activities in Ps. aeruginosa and their in-vitro control by choline, acetylcholine and betaine." Mol Cell Biochem 50(2);149-55. PMID: 6406829
Meskys01: Meskys R, Harris RJ, Casaite V, Basran J, Scrutton NS (2001). "Organization of the genes involved in dimethylglycine and sarcosine degradation in Arthrobacter spp.: implications for glycine betaine catabolism." Eur J Biochem 268(12);3390-8. PMID: 11422368
Osteras98: Osteras M, Boncompagni E, Vincent N, Poggi MC, Le Rudulier D (1998). "Presence of a gene encoding choline sulfatase in Sinorhizobium meliloti bet operon: choline-O-sulfate is metabolized into glycine betaine." Proc Natl Acad Sci U S A 1998;95(19);11394-9. PMID: 9736747
Anfora07: Anfora AT, Haugen BJ, Roesch P, Redford P, Welch RA (2007). "Roles of serine accumulation and catabolism in the colonization of the murine urinary tract by Escherichia coli CFT073." Infect Immun 75(11);5298-304. PMID: 17785472
Beckmann97: Beckmann K, Dzuibany C, Biehler K, Fock H, Hell R, Migge A, Becker TW (1997). "Photosynthesis and fluorescence quenching, and the mRNA levels of plastidic glutamine synthetase or of mitochondrial serine hydroxymethyltransferase (SHMT) in the leaves of the wild-type and of the SHMT-deficient stm mutant of Arabidopsis thaliana in relation to the rate of photorespiration." Planta 202(3);379-86. PMID: 9232907
Brizio00: Brizio C, Otto A, Brandsch R, Passarella S, Barile M (2000). "A protein factor of rat liver mitochondrial matrix involved in flavinylation of dimethylglycine dehydrogenase." Eur J Biochem 267(14);4346-54. PMID: 10880957
Brizio04: Brizio C, Brandsch R, Bufano D, Pochini L, Indiveri C, Barile M (2004). "Over-expression in Escherichia coli, functional characterization and refolding of rat dimethylglycine dehydrogenase." Protein Expr Purif 37(2);434-42. PMID: 15358367
Burman04: Burman JD, Harris RL, Hauton KA, Lawson DM, Sawers RG (2004). "The iron-sulfur cluster in the L-serine dehydratase TdcG from Escherichia coli is required for enzyme activity." FEBS Lett 576(3);442-4. PMID: 15498577
Capela01: Capela D, Barloy-Hubler F, Gouzy J, Bothe G, Ampe F, Batut J, Boistard P, Becker A, Boutry M, Cadieu E, Dreano S, Gloux S, Godrie T, Goffeau A, Kahn D, Kiss E, Lelaure V, Masuy D, Pohl T, Portetelle D, Puhler A, Purnelle B, Ramsperger U, Renard C, Thebault P, Vandenbol M, Weidner S, Galibert F (2001). "Analysis of the chromosome sequence of the legume symbiont Sinorhizobium meliloti strain 1021." Proc Natl Acad Sci U S A 98(17);9877-82. PMID: 11481430
Chen94: Chen D, Swenson RP (1994). "Cloning, sequence analysis, and expression of the genes encoding the two subunits of the methylotrophic bacterium W3A1 electron transfer flavoprotein." J Biol Chem 269(51);32120-30. PMID: 7798207
Chistoserdova94: Chistoserdova LV, Lidstrom ME (1994). "Genetics of the serine cycle in Methylobacterium extorquens AM1: cloning, sequence, mutation, and physiological effect of glyA, the gene for serine hydroxymethyltransferase." J Bacteriol 176(21);6759-62. PMID: 7961431
Cicchillo04: Cicchillo RM, Baker MA, Schnitzer EJ, Newman EB, Krebs C, Booker SJ (2004). "Escherichia coli L-serine deaminase requires a [4Fe-4S] cluster in catalysis." J Biol Chem 279(31);32418-25. PMID: 15155761
Contestabile00: Contestabile R, Angelaccio S, Bossa F, Wright HT, Scarsdale N, Kazanina G, Schirch V (2000). "Role of tyrosine 65 in the mechanism of serine hydroxymethyltransferase." Biochemistry 39(25);7492-500. PMID: 10858298
Cook85a: Cook RJ, Misono KS, Wagner C (1985). "The amino acid sequences of the flavin-peptides of dimethylglycine dehydrogenase and sarcosine dehydrogenase from rat liver mitochondria." J Biol Chem 260(24);12998-3002. PMID: 4055729
DelgadoReyes01: Delgado-Reyes CV, Wallig MA, Garrow TA (2001). "Immunohistochemical detection of betaine-homocysteine S-methyltransferase in human, pig, and rat liver and kidney." Arch Biochem Biophys 393(1);184-6. PMID: 11516176
Delle94: Delle Fratte S, Iurescia S, Angelaccio S, Bossa F, Schirch V (1994). "The function of arginine 363 as the substrate carboxyl-binding site in Escherichia coli serine hydroxymethyltransferase." Eur J Biochem 225(1);395-401. PMID: 7925461
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