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Aquifex aeolicus VF5 Pathway: creatinine degradation II

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Superclasses: Degradation/Utilization/Assimilation Amines and Polyamines Degradation Creatinine Degradation

Pathway Summary from MetaCyc:
General Background

Creatine is a naturally occurring amino acid that is used to store and supply energy to muscle cells in vertebrates. The name creatine is derived from the Greek kreas (flesh). The enzyme creatine kinase adds a phosphate to creatine (see creatine + ATP ↔ creatine-phosphate + ADP + H+), generating creatine-phosphate. The energy stored in the creatine-phosphate bond can be reused when creatine phosphate reacts with ADP to regenerate ATP. In fast-twitch skeletal muscles, a large pool of creatine-phosphate is available for immediate regeneration of ATP hydrolyzed during short periods of intense work. Because of the high cytosolic creatine kinase activity in these muscles, the creatine kinase reaction remains in a near-equilibrium state, keeping ADP and ATP almost constant, and buffering the cytosolic phosphorylation potential that is crucial for proper functioning of cellular ATPases [Wyss00]. Creatine is found in the blood, brain, and muscle of many organisms. Creatinine is a breakdown product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body in a nonenzymatic process. Creatinine is not reabsorbed, and is mainly filtered by the kidney and excreted in the urine. Both creatine and creatinine can be used by microorganisms as carbon and nitrogen sources [Tsuru77]. At least three different routes by which different microbes degrade creatinine have been discovered [Wyss00].

About This Pathway

A second metabolic pathway for the degradation of creatinine was discovered in Pseudomonas putida 77 [Yamada85], and later detected in several organisms, including Pseudomonas, Brevibacterium, Moraxella , Micrococcus,Arthrobacter, Clostridium and Tissierella [Hermann92, Wyss00].

In this pathway, creatinine is not hydrolyzed back to creatine. Instead, it is deaminated to N-methylhydantoin, releasing an amonia molecule, by the action of creatinine deaminase (also known as creatinine iminohydrolase). In all organisms studied so far, a single enzyme shares both creatinine deaminase and cytosine deaminase [Wyss00]. N-methylhydantoin is then hydrolyzed to N-carbamoylsarcosine, by the action of N-methylhydantoin amidohydrolase, at the expense of one ATP molecule [Kim87]. N-carbamoylsarcosine is deaminated further to sarcosine by N-carbamoylsarcosine amidohydrolase, releasing a second ammonia molecule. In the last step of this pathway, which is shared with creatinine degradation I, sarcosine is hydrolyzed to glycine and formaldehyde, by either sarcosine dehydrogenase or sarcosine oxidase.

All of the enzyme involved in this pathway are highly inducible when the bacteria grow on creatinine as the main source of nitrogen, and in some cases, carbon.

Many organisms, including Bacillus, Corynebacterium, Flavobacterium, Escherichia and Proteus as well as some fungi (including Cryptococcus neoformans and Cryptococcus bacillisporous) were reported to be able to catalyze only the first step of this pathway, accumulating N-methylhydantoin. Apparently, the reason for this wide distribution is the fact that the enzyme catalyzing this reaction, creatinine deiminase, is the abundant enzyme cytosine deaminase [Kim87a]. Since most of these organisms lack the enzymes that catalyze subsequent steps, this first step may be considered a side effect of cytosine deaminase rather than a true degradation pathway [Wyss00].

Since mammals do not have a creatininase function, creatinine is absorberd in the kidneys and released into urine. As a result, measuring the level of creatinine in the blood and urine provides an accurate measure of renal function. Assays for measuring creatinine concentration based on the enzymes that participate in this pathway have been developed [Siedel88, Ogawa95].

Pathway Evidence Glyph:

Key to pathway glyph edge colors: ?

  An enzyme catalyzing this reaction is present in this organism
  No enzyme catalyzing this reaction has been identified in this organism
  The reaction and any enzyme that catalyzes it (if one has been identified) is unique to this pathway

Created in MetaCyc 08-Sep-2005 by Caspi R , SRI International
Imported from MetaCyc 08-Aug-2014 by Subhraveti P , SRI International


Hermann92: Hermann M, Knerr HJ, Mai N, Gross A, Kaltwasser H (1992). "Creatinine and N-methylhydantoin degradation in two newly isolated Clostridium species." Arch Microbiol 157(5);395-401. PMID: 1510564

Kim87: Kim JM, Shimizu S, Yamada H (1987). "Amidohydrolysis of N-methylhydantoin coupled with ATP hydrolysis." Biochem Biophys Res Commun 142(3);1006-12. PMID: 3827889

Kim87a: Kim, J. M., Shimizu, S., Yamada, H. (1987). "Cytosine demainase that hydrolyzes creatinine to N-methylhydantoin in various cytosine deaminase-forming microorganisms." Arch. Microbiol. 147:58-63.

Ogawa95: Ogawa J, Nirdnoy W, Tabata M, Yamada H, Shimizu S (1995). "A new enzymatic method for the measurement of creatinine involving a novel ATP-dependent enzyme, N-methylhydantoin amidohydrolase." Biosci Biotechnol Biochem 59(12);2292-4. PMID: 8611752

Siedel88: Siedel, J., Deeg, R., Seidel, H., Moellering, H., Staepels, J., Gauhl, H., Ziegenhorn, J. (1988). "Fully enzymatic colorimetric assay of serum and urine creatinine which obviates the need for sample blank measurements." Anal. Letters 21:1009-1017.

Tsuru77: Tsuru, D. (1977). "On the catabolism of creatinine, and the related enzymes in microorganisms." Nucleic Acids Amino Acids 35:31-37.

Wyss00: Wyss M, Kaddurah-Daouk R (2000). "Creatine and creatinine metabolism." Physiol Rev 80(3);1107-213. PMID: 10893433

Yamada85: Yamada, H., Shimizu, S., Kim, J. M., Shinmen, Y., Sakai, T. (1985). "A novel metabolic pathway for creatinine degradation in Pseudomonas putida 77." FEMS Microbiol. Let. 30:337-340.

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

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

Ishizaki06: Ishizaki K, Schauer N, Larson TR, Graham IA, Fernie AR, Leaver CJ (2006). "The mitochondrial electron transfer flavoprotein complex is essential for survival of Arabidopsis in extended darkness." Plant J 47(5);751-60. PMID: 16923016

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

Mayhew74: Mayhew SG, Whitfield CD, Ghisla S, Schuman-Jorns M (1974). "Identification and properties of new flavins in electron-transferring flavoprotein from Peptostreptococcus elsdenii and pig-liver glycolate oxidase." Eur J Biochem 44(2);579-91. PMID: 4365840

Roberts96: Roberts DL, Frerman FE, Kim JJ (1996). "Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution." Proc Natl Acad Sci U S A 93(25);14355-60. PMID: 8962055

Roberts99: Roberts DL, Salazar D, Fulmer JP, Frerman FE, Kim JJ (1999). "Crystal structure of Paracoccus denitrificans electron transfer flavoprotein: structural and electrostatic analysis of a conserved flavin binding domain." Biochemistry 38(7);1977-89. PMID: 10026281

Sato03: Sato K, Nishina Y, Shiga K (2003). "Purification of electron-transferring flavoprotein from Megasphaera elsdenii and binding of additional FAD with an unusual absorption spectrum." J Biochem 134(5);719-29. PMID: 14688238

Whitfield74: Whitfield CD, Mayhew SG (1974). "Purification and properties of electron-transferring flavoprotein from Peptostreptococcus elsdenii." J Biol Chem 249(9);2801-10. PMID: 4364030

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