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MetaCyc Pathway: choline degradation I
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: choline degradation I

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: choline betaine anabolism

Superclasses: BiosynthesisAmines and Polyamines BiosynthesisBetaine Biosynthesis
Degradation/Utilization/AssimilationAmines and Polyamines DegradationCholine Degradation

Some taxa known to possess this pathway include : Homo sapiens, Hordeum vulgare, Pseudomonas aeruginosa, Pseudomonas putida, Sinorhizobium meliloti Rm2011

Expected Taxonomic Range: Metazoa, Proteobacteria, Viridiplantae

General Background

Bacteria and plants often accumulates choline, since it can easily be converted to glycine betaine, a common osmoprotectant [Le84]. Many organisms can also use choline as a sole source for both carbon and nitrogen by catabolizing it via glycine betaine [Smith88, Lisa83] (see glycine betaine degradation I).

While the conversion of choline to glycine betaine for the purpose of accumulating the latter as an osmoprotectant is considered biosynthetic (see glycine betaine biosynthesis I (Gram-negative bacteria), glycine betaine biosynthesis II (Gram-positive bacteria), and glycine betaine biosynthesis III (plants)), the conversion of choline to glycine betaine for the purpose of further catabolism should be considered as a choline degradation pathway. Two such pathways have been demonstrated: Certain Gram-negative bacteria such as Synrhizobium meliloti, as well as some plants, degrade choline to glycine betaine using a combination of two different dehydrogenases (this pathway), while certain Gram-positive bacteria, as well as certain fungi, achieve this by the activity of a single enzyme, choline oxidase (see choline degradation II).

About This Pathway

The conversion of choline to glycine betaine in this pathway is performed by the action of two dehydrogenases. Choline dehydrogenase converts choline to betaine aldehyde, while betaine aldehyde dehydrogenase converts the aldehyde to glycine betaine.

It has been proposed that choline degradation in R. meliloti can be used as a mechanism for osmoregulation. When the bacteria grow at normal osmolarity conditions, they degrade choline, using it as a carbon and nitrogen source. However, under inhibiting osmotical conditions, enzyme activities that lead to glycine betaine degradation decrease, while 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 [Smith88].

Similarly, while Pseudomonas aeruginosa catabolizes both choline and glycine betaine under low osmolarity conditions, it accumulates the latter under high osmolarity, presumably by down regulating the enzyme glycine betaine transmethylase, which converts glycine betaine to N,N-dimethylglycine (DMG), while maintaining the activity of the enzymes of this pathway [Serra02].

In the plant Hordeum vulgare the formation and accumulation of glycine betaine via choline degradation was studied under salt and low temperature stress conditions [Mitsuya11]. GB accumulation increased under salt stress. The first step is catalyzed by peroxisomal choline monooxygenase (CMO) which converts choline to glycine betaine with NADPH as the co-factor. In barley, interestingly, this enzyme's localization is restricted to perioxisomes whereas in spinach and other higher plants it is localized in the chloroplast. Plant choline degradation pathways differ from bacterial pathways primarily due to the cellular localization of the two enzymes [Fujiwara08]. This in turn determines how and when the enzymes are regulated under stress conditions and during recycling of compounds. Expression pattern of the two enzymes, CMO and betaine aldehyde dehydrogenase (BADH), varied; CMO was abundant in leaves and BADH was abundant in awn and florets [Ishitani95]. As many plants do not synthesis GB, studies are underway to find out how and where this compound is produced, transported and degraded [Wu11, Zhang08] so effective bioengineering strategies can be worked out.

Superpathways: choline-O-sulfate degradation

Variants: β-alanine betaine biosynthesis, choline degradation II, choline degradation III, choline degradation IV, glycine betaine biosynthesis I (Gram-negative bacteria), glycine betaine biosynthesis II (Gram-positive bacteria), glycine betaine biosynthesis III (plants), glycine betaine biosynthesis IV (from glycine), glycine betaine biosynthesis V (from glycine)

Created 11-Aug-1998 by Ying HC, SRI International
Revised 23-May-2005 by Caspi R, SRI International


Fujiwara08: Fujiwara T, Hori K, Ozaki K, Yokota Y, Mitsuya S, Ichiyanagi T, Hattori T, Takabe T (2008). "Enzymatic characterization of peroxisomal and cytosolic betaine aldehyde dehydrogenases in barley." Physiol Plant 134(1);22-30. PMID: 18429940

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

Le84: Le Rudulier, D., Strom, A. R., Dandekar, A. M., Smith, L. T. (1984). "Molecular biology of osmoregulation." Science 224:1064-1068.

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

Mitsuya11: Mitsuya S, Kuwahara J, Ozaki K, Saeki E, Fujiwara T, Takabe T (2011). "Isolation and characterization of a novel peroxisomal choline monooxygenase in barley." Planta. PMID: 21769646

Serra02: Serra AL, Mariscotti JF, Barra JL, Lucchesi GI, Domenech CE, Lisa AT (2002). "Glycine betaine transmethylase mutant of Pseudomonas aeruginosa." J Bacteriol 184(15);4301-3. PMID: 12107149

Smith88: Smith LT, Pocard JA, Bernard T, Le Rudulier D (1988). "Osmotic control of glycine betaine biosynthesis and degradation in Rhizobium meliloti." J Bacteriol 170(7);3142-9. PMID: 3290197

Wu11: Wu S, Su Q, An L, Ma S (2011). "A choline monooxygenase gene promoter from Salicornia europaea increases expression of the beta-glucuronidase gene under abiotic stresses in tobacco (Nicotiana tabacum L.)." Indian J Biochem Biophys 48(3);170-4. PMID: 21793308

Zhang08: Zhang Y, Yin H, Li D, Zhu W, Li Q (2008). "Functional analysis of BADH gene promoter from Suaeda liaotungensis K." Plant Cell Rep 27(3);585-92. PMID: 17924116

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

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

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

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

Canovas00: Canovas D, Vargas C, Kneip S, Moron MJ, Ventosa A, Bremer E, Nieto JJ (2000). "Genes for the synthesis of the osmoprotectant glycine betaine from choline in the moderately halophilic bacterium Halomonas elongata DSM 3043, USA." Microbiology 146 ( Pt 2);455-63. PMID: 10708384

deRidder73: de Ridder JJ, Kleverlaan NT, Verdouw-Chamalaun CV, Schippers PG, van Dam K (1973). "Uncoupler-stimulated oxidation of choline by rat-liver mitochondria." Biochim Biophys Acta 325(3);397-405. PMID: 4778287

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

Gadda03: Gadda G, McAllister-Wilkins EE (2003). "Cloning, expression, and purification of choline dehydrogenase from the moderate halophile Halomonas elongata." Appl Environ Microbiol 69(4);2126-32. PMID: 12676692

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

Haubrich81: Haubrich DR, Gerber NH (1981). "Choline dehydrogenase. Assay, properties and inhibitors." Biochem Pharmacol 30(21);2993-3000. PMID: 6797435

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

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

Landfald86: Landfald B, Strom AR (1986). "Choline-glycine betaine pathway confers a high level of osmotic tolerance in Escherichia coli." J Bacteriol 1986;165(3);849-55. PMID: 3512525

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Mandon03: Mandon K, Osteras M, Boncompagni E, Trinchant JC, Spennato G, Poggi MC, Le Rudulier D (2003). "The Sinorhizobium meliloti glycine betaine biosynthetic genes (betlCBA) are induced by choline and highly expressed in bacteroids." Mol Plant Microbe Interact 16(8);709-19. PMID: 12906115

Marchitti08: Marchitti SA, Brocker C, Stagos D, Vasiliou V (2008). "Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily." Expert Opin Drug Metab Toxicol 4(6);697-720. PMID: 18611112

Mills06: Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA, Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT (2006). "Mutations in antiquitin in individuals with pyridoxine-dependent seizures." Nat Med 12(3);307-9. PMID: 16491085

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

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by Pathway Tools version 19.5 (software by SRI International) on Sun May 1, 2016, biocyc14.