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.
Synonyms: glycine betaine biosynthesis
|Superclasses:||Biosynthesis → Amines and Polyamines Biosynthesis → Betaine Biosynthesis|
Expected Taxonomic Range: Viridiplantae
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. In addition to its osmoprotectant activity, glycine betaine is also a potent protectant against mutagenic compounds [Ji03, Monobe05] and radiation-induced damage [Monobe03].
Glycine betaine can either be taken up directly from the environment, or synthesized. A common biosynthesis pathway for glycine betaine is from choline, utilizing a two-step pathway with betaine aldehyde as intermediate. This pathway is conserved in bacteria and plants, but shows divergence in the enzymes involved. Gram-negative bacteria, Gram-positive bacteria and higher plants all use a betaine aldehyde dehydrogenase (EC 18.104.22.168) to catalyze the conversion of betaine aldehyde to glycine betaine. The choline-to-betaine aldehyde reaction, however, is divergent: Gram-negative bacteria such as Escherichia coli, Pseudomonas aeruginosa, and Sinorhizobium meliloti utilize a choline dehydrogenase (EC 22.214.171.124) (see glycine betaine biosynthesis I (Gram-negative bacteria)), Gram-positive bacteria, such as Bacillus subtilis, use an alcohol dehydrogenase (EC 126.96.36.199) (see glycine betaine biosynthesis II (Gram-positive bacteria)), while high plants use a choline monooxygenase (EC 188.8.131.52) (this pathway).
Certain Gram-positive bacteria, such as Arthrobacter pascens and Arthrobacter globiformis, as well as the fungus Cylindrocarpon didymun, use yet another enzyme to catalyze this conversion: they use a soluble choline oxidase that catalyzes both steps (see choline degradation II).
There exists at least one more variation for the synthesis of glycine betaine, which is found in several halotolerant bacteria. The pathway was found in Halorhodospira halochloris (previously known as Ectothiorhodospira halochloris) and several other organisms, which synthesize glycine betaine from glycine through a series of methylation reactions [Nyyssola00] (see glycine betaine biosynthesis IV (from glycine)). However, since methylation reactions are among the most energy-consuming processes in nature (the regeneration of one active methyl group of S-adenosylmethionine costs the cell 12 ATP equivalents), it is not surprising that this pathway is less common.
About This Pathway
Glycine betain biosynthesis in plants differs from that in bacteria and animal. Plants convert choline to betaine aldehyde by the activity of choline monooxygenase, a Rieske type iron-sulfur-containing enzyme, whereas bacteria and animals catalyze this reaction utilizing either choline dehydrogenase or choline oxidase.
The two enzymes of this pathway have been characterized in plants including spinach and sugar beet. Arabidopsis is generally considered a non-glycine betaine accumulating plant [Hibino02], yet data suggests the endogenous glycine betaine level can be induced by cold acclimation and water stress [Xing01].
Variants: β-alanine betaine biosynthesis , choline degradation I , choline-O-sulfate degradation , glycine betaine biosynthesis I (Gram-negative bacteria) , glycine betaine biosynthesis II (Gram-positive bacteria) , glycine betaine biosynthesis IV (from glycine) , glycine betaine biosynthesis V (from glycine)
Unification Links: AraCyc:PWY1F-353
Hibino02: Hibino T, Waditee R, Araki E, Ishikawa H, Aoki K, Tanaka Y, Takabe T (2002). "Functional characterization of choline monooxygenase, an enzyme for betaine synthesis in plants." J Biol Chem 277(44);41352-60. PMID: 12192001
Nyyssola00: Nyyssola A, Kerovuo J, Kaukinen P, von Weymarn N, Reinikainen T (2000). "Extreme halophiles synthesize betaine from glycine by methylation." J Biol Chem 2000;275(29);22196-201. PMID: 10896953
Boch97: Boch J, Nau-Wagner G, Kneip S, Bremer E (1997). "Glycine betaine aldehyde dehydrogenase from Bacillus subtilis: characterization of an enzyme required for the synthesis of the osmoprotectant glycine betaine." Arch Microbiol 168(4);282-9. PMID: 9297465
Boyd91: Boyd LA, Adam L, Pelcher LE, McHughen A, Hirji R, Selvaraj G (1991). "Characterization of an Escherichia coli gene encoding betaine aldehyde dehydrogenase (BADH): structural similarity to mammalian ALDHs and a plant BADH." Gene 103(1);45-52. PMID: 1879697
Brocker10: Brocker C, Lassen N, Estey T, Pappa A, Cantore M, Orlova VV, Chavakis T, Kavanagh KL, Oppermann U, Vasiliou V (2010). "Aldehyde dehydrogenase 7A1 (ALDH7A1) is a novel enzyme involved in cellular defense against hyperosmotic stress." J Biol Chem 285(24);18452-63. PMID: 20207735
Falkenberg90: Falkenberg P, Strom AR (1990). "Purification and characterization of osmoregulatory betaine aldehyde dehydrogenase of Escherichia coli." Biochim Biophys Acta 1990;1034(3);253-9. PMID: 2194570
Gell02: Gell D, Kong Y, Eaton SA, Weiss MJ, Mackay JP (2002). "Biophysical characterization of the alpha-globin binding protein alpha-hemoglobin stabilizing protein." J Biol Chem 277(43);40602-9. PMID: 12192002
Gruez04: Gruez A, Roig-Zamboni V, Grisel S, Salomoni A, Valencia C, Campanacci V, Tegoni M, Cambillau C (2004). "Crystal structure and kinetics identify Escherichia coli YdcW gene product as a medium-chain aldehyde dehydrogenase." J Mol Biol 343(1);29-41. PMID: 15381418
Incharoensakdi00: Incharoensakdi A, Matsuda N, Hibino T, Meng YL, Ishikawa H, Hara A, Funaguma T, Takabe T, Takabe T (2000). "Overproduction of spinach betaine aldehyde dehydrogenase in Escherichia coli. Structural and functional properties of wild-type, mutants and E. coli enzymes." Eur J Biochem 267(24);7015-23. PMID: 11106411
Ishitani95: Ishitani M, Nakamura T, Han SY, Takabe T (1995). "Expression of the betaine aldehyde dehydrogenase gene in barley in response to osmotic stress and abscisic acid." Plant Mol Biol 27(2);307-15. PMID: 7888620
Lambou13: Lambou K, Pennati A, Valsecchi I, Tada R, Sherman S, Sato H, Beau R, Gadda G, Latge JP (2013). "Pathway of glycine betaine biosynthesis in Aspergillus fumigatus." Eukaryot Cell 12(6);853-63. PMID: 23563483
Missihoun11: Missihoun TD, Schmitz J, Klug R, Kirch HH, Bartels D (2011). "Betaine aldehyde dehydrogenase genes from Arabidopsis with different sub-cellular localization affect stress responses." Planta 233(2);369-82. PMID: 21053011
Mou02: Mou Z, Wang X, Fu Z, Dai Y, Han C, Ouyang J, Bao F, Hu Y, Li J (2002). "Silencing of phosphoethanolamine N-methyltransferase results in temperature-sensitive male sterility and salt hypersensitivity in Arabidopsis." Plant Cell 14(9);2031-43. PMID: 12215503
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
Park06: Park YJ, Yoo CB, Choi SY, Lee HB (2006). "Purifications and characterizations of a ferredoxin and its related 2-oxoacid:ferredoxin oxidoreductase from the hyperthermophilic archaeon, Sulfolobus solfataricus P1." J Biochem Mol Biol 39(1);46-54. PMID: 16466637
Pocard97: Pocard JA, Vincent N, Boncompagni E, Smith LT, Poggi MC, Le Rudulier D (1997). "Molecular characterization of the bet genes encoding glycine betaine synthesis in Sinorhizobium meliloti 102F34." Microbiology 1997;143 ( Pt 4);1369-79. PMID: 9141699
Rathinasabapath97: Rathinasabapathi B, Burnet M, Russell BL, Gage DA, Liao PC, Nye GJ, Scott P, Golbeck JH, Hanson AD (1997). "Choline monooxygenase, an unusual iron-sulfur enzyme catalyzing the first step of glycine betaine synthesis in plants: prosthetic group characterization and cDNA cloning." Proc Natl Acad Sci U S A 94(7);3454-8. PMID: 9096415
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