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discounted EARLY registration ends Dec 31, 2014
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discounted EARLY registration ends Dec 31, 2014
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MetaCyc Pathway: acetone degradation I (to methylglyoxal)

Enzyme View:

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 Fatty Acid and Lipids Degradation Acetone Degradation

Some taxa known to possess this pathway include ? : Homo sapiens , Mammalia , Mus musculus , Rattus norvegicus

Expected Taxonomic Range: Mammalia

Summary:
General Background

There are two main sources for acetone production in organisms: the decarboxylation of acetoacetate (EC 4.1.1.4) and the dehydrogenation of isopropanol (EC 1.1.1.80). Acetoacetate decarboxylation is the major source of acetone in mammals, and arises from either lipolysis or amino acid degradation [Kalapos03]. Acetoacetate decarboxylation may happen either enzymatically or non-enzymatically. The enzyme responsible for this reaction, acetoacetate decarboxylase, was first identified in the bacterium Clostridium acetobutylicum. However, the existence of this enzymatic activity in mammals, including rat and humans has been documented [vanStekelenburg72, Koorevaar76].

The conversion of isopropanol to acetone is catalyzed by the class I isozymes of the hepatic alcohol dehydrogenase family [Nordmann73, Kalapos03]. Over the years, differences in the activity of enzymes from different sources have been noted [Davis84]. For example, horse liver alcohol dehydrogenase could not react with isopropanol [Theorell51].

About This Pathway

Once acetone is formed, it can be metabolized in several pathways. One of these pathways involves its conversion to methylglyoxal in two consecutive steps via acetol as intermediate.

The production of methylglyoxal from acetone was proposed in 1984, based on studies of acetone metabolism in the rat [Casazza84]. The possible role of cytochrome P450s in acetone metabolism was recognized in 1980 [Coleman80], and cytochrome P450 2E1 was identified as both the acetone and acetol monooxygenases in liver microsomes from rabbit, rat and mouse [Koop85, Johansson86, Bondoc99].

This pathway is inducible, and can be induced by several agents (acetone, ethanol, pyrazole, imidazole, etc.) or under different physiological and pathological circumstances, such as fasting or diabetes mellitus [Gonzalez89].

Variants: acetone degradation II (to acetoacetate) , acetone degradation III (to propane-1,2-diol)

Credits:
Created 15-Jan-2007 by Caspi R , SRI International


References

Bondoc99: Bondoc FY, Bao Z, Hu WY, Gonzalez FJ, Wang Y, Yang CS, Hong JY (1999). "Acetone catabolism by cytochrome P450 2E1: studies with CYP2E1-null mice." Biochem Pharmacol 58(3);461-3. PMID: 10424765

Casazza84: Casazza JP, Felver ME, Veech RL (1984). "The metabolism of acetone in rat." J Biol Chem 259(1);231-6. PMID: 6706932

Coleman80: Coleman DL (1980). "Acetone metabolism in mice: increased activity in mice heterozygous for obesity genes." Proc Natl Acad Sci U S A 77(1);290-3. PMID: 6928621

Davis84: Davis PL, Dal Cortivo LA, Maturo J (1984). "Endogenous isopropanol: forensic and biochemical implications." J Anal Toxicol 8(5):209-12. PMID: 6389978

Gonzalez89: Gonzalez FJ, Matsunaga T, Nagata K (1989). "Structure and regulation of P-450s in the rat P450IIA gene subfamily." Drug Metab Rev 20(2-4);827-37. PMID: 2806080

Johansson86: Johansson I, Eliasson E, Norsten C, Ingelman-Sundberg M (1986). "Hydroxylation of acetone by ethanol- and acetone-inducible cytochrome P-450 in liver microsomes and reconstituted membranes." FEBS Lett 196(1);59-64. PMID: 3943633

Kalapos03: Kalapos MP (2003). "On the mammalian acetone metabolism: from chemistry to clinical implications." Biochim Biophys Acta 1621(2);122-39. PMID: 12726989

Koop85: Koop DR, Casazza JP (1985). "Identification of ethanol-inducible P-450 isozyme 3a as the acetone and acetol monooxygenase of rabbit microsomes." J Biol Chem 260(25);13607-12. PMID: 4055750

Koorevaar76: Koorevaar G, Van Stekelenburg GJ (1976). "Mammalian acetoacetate decarboxylase activity. Its distribution in subfractions of human albumin and occurrence in various tissues of the rat." Clin Chim Acta 71(2);173-83. PMID: 963888

Nordmann73: Nordmann R, Ribiere C, Rouach H, Beauge F, Giudicelli Y, Nordmann J (1973). "Metabolic pathways involved in the oxidation of isopropanol into acetone by the intact rat." Life Sci 13(7);919-32. PMID: 4358273

Theorell51: Theorell, H., Bonnichsen, R. (1951). "Studies on liver alcohol dehydrogenase I. Equilibria and initial reaction velocities." Acta Chem. Scand. 5: 1105-1126.

vanStekelenburg72: van Stekelenburg GJ, Koorevaar G (1972). "Evidence for the existence of mammalian acetoacetate decarboxylase: with special reference to human blood serum." Clin Chim Acta 39(1);191-9. PMID: 4624981

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

Asai96: Asai H, Imaoka S, Kuroki T, Monna T, Funae Y (1996). "Microsomal ethanol oxidizing system activity by human hepatic cytochrome P450s." J Pharmacol Exp Ther 277(2);1004-9. PMID: 8627510

Autor70: Autor AP, Fridovich I (1970). "The interactions of acetoacetate decarboxylase with carbonyl compounds, hydrogen cyanide, and an organic mercurial." J Biol Chem 1970;245(20);5214-22. PMID: 5469163

Bohren89: Bohren KM, Bullock B, Wermuth B, Gabbay KH (1989). "The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases." J Biol Chem 264(16);9547-51. PMID: 2498333

Boleda93: Boleda MD, Saubi N, Farres J, Pares X (1993). "Physiological substrates for rat alcohol dehydrogenase classes: aldehydes of lipid peroxidation, omega-hydroxyfatty acids, and retinoids." Arch Biochem Biophys 307(1);85-90. PMID: 8239669

Bosron87: Bosron WF, Li TK (1987). "Catalytic properties of human liver alcohol dehydrogenase isoenzymes." Enzyme 37(1-2);19-28. PMID: 3569190

Boyer72: Boyer PD, editor (1972). "Chapter 8- Acetoacetate Decarboxylase." The Enzymes, Third Edition, Volume Six, Carboxylation and decarboxylation (nonoxidative) isomerization, Academic Press New York.

Burnell87: Burnell JC, Carr LG, Dwulet FE, Edenberg HJ, Li TK, Bosron WF (1987). "The human beta 3 alcohol dehydrogenase subunit differs from beta 1 by a Cys for Arg-369 substitution which decreases NAD(H) binding." Biochem Biophys Res Commun 146(3);1127-33. PMID: 3619918

Carr89: Carr LG, Xu Y, Ho WH, Edenberg HJ (1989). "Nucleotide sequence of the ADH2(3) gene encoding the human alcohol dehydrogenase beta 3 subunit." Alcohol Clin Exp Res 13(4);594-6. PMID: 2679216

Chrostek03: Chrostek L, Jelski W, Szmitkowski M, Puchalski Z (2003). "Gender-related differences in hepatic activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in humans." J Clin Lab Anal 17(3);93-6. PMID: 12696080

Chrostek03a: Chrostek L, Jelski W, Szmitkowski M, Puchalski Z (2003). "Alcohol dehydrogenase (ADH) isoenzymes and aldehyde dehydrogenase (ALDH) activity in the human pancreas." Dig Dis Sci 48(7);1230-3. PMID: 12870777

Cotton88: Cotton RW, Goldman D (1988). "Review of the molecular biology of the human alcohol dehydrogenase genes and gene products." Adv Alcohol Subst Abuse 7(3-4);171-82. PMID: 3066190

Danielsson94: Danielsson O, Shafqat J, Estonius M, Jornvall H (1994). "Alcohol dehydrogenase class III contrasted to class I. Characterization of the cyclostome enzyme, the existence of multiple forms as for the human enzyme, and distant cross-species hybridization." Eur J Biochem 225(3);1081-8. PMID: 7957198

Davis93: Davis JF, Felder MR (1993). "Mouse ethanol-inducible cytochrome P-450 (P450IIE1). Characterization of cDNA clones and testosterone induction in kidney tissue." J Biol Chem 268(22);16584-9. PMID: 8344939

Day91: Day CP, Bashir R, James OF, Bassendine MF, Crabb DW, Thomasson HR, Li TK, Edenberg HJ (1991). "Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage." Hepatology 14(5);798-801. PMID: 1937384

Duester86: Duester G, Smith M, Bilanchone V, Hatfield GW (1986). "Molecular analysis of the human class I alcohol dehydrogenase gene family and nucleotide sequence of the gene encoding the beta subunit." J Biol Chem 261(5);2027-33. PMID: 2935533

Duester99: Duester G, Farres J, Felder MR, Holmes RS, Hoog JO, Pares X, Plapp BV, Yin SJ, Jornvall H (1999). "Recommended nomenclature for the vertebrate alcohol dehydrogenase gene family." Biochem Pharmacol 58(3);389-95. PMID: 10424757

Fairbrother98: Fairbrother KS, Grove J, de Waziers I, Steimel DT, Day CP, Crespi CL, Daly AK (1998). "Detection and characterization of novel polymorphisms in the CYP2E1 gene." Pharmacogenetics 8(6);543-52. PMID: 9918138

Gerischer90: Gerischer U, Durre P (1990). "Cloning, sequencing, and molecular analysis of the acetoacetate decarboxylase gene region from Clostridium acetobutylicum." J Bacteriol 1990;172(12);6907-18. PMID: 2254264

Gillam94: Gillam EM, Guo Z, Guengerich FP (1994). "Expression of modified human cytochrome P450 2E1 in Escherichia coli, purification, and spectral and catalytic properties." Arch Biochem Biophys 312(1);59-66. PMID: 8031147

Grant03a: Grant AW, Steel G, Waugh H, Ellis EM (2003). "A novel aldo-keto reductase from Escherichia coli can increase resistance to methylglyoxal toxicity." FEMS Microbiol Lett 218(1);93-9. PMID: 12583903

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Report Errors or Provide Feedback
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 SRI International Pathway Tools version 18.5 on Wed Dec 17, 2014, biocyc13.