Propionic acid, metabolism

Propionyl-CoA carboxylase catalyzes the carboxylation of propionyl-CoA to form D-methylmalonyl-CoA in propionic acid metabolism, as shown in the reaction that follows ... 

Studies on Congenital Disorders in Propionic Acid Metabolism Using Gas Chromatography and Mass Spectrometry GC-MS News 5(4) 2-3 (1977) CA 88 185472p... 

Stadtman, E. R. and Vagelos, P. R. (1958) Propionic acid metabolism. International Symposium on Enzyme Chemistry, p. 86, Tokyo and Kyoto, 1957, Pan-Pacific Press, Tokyo. 

Vagelos, P. R. and Earl, J. M. (1959) Propionic acid metabolism. HI. jS-Hydroxpropionyl coenzyme A and malonyl semialdehyde coenzyme A, intermediates in propionate oxidation by Clostridium kluy-veri. J. Biol. Chem. 234, 2272. 

Hill, H.Z. and Goodman, S.I. (1974), Detection of inborn errors of metabolism. II. Defects in propionic acid metabolism. Clin. Genet., 6,73. 

The metabolism of carfentrazone-ethyl in animals and plants is similar. The major plant metabolites are carfentrazone-chloropropionic acid (C-CI-PAc), 3-desmethylcarfentrazone-chloropropionic acid (DM-C-CI-PAc), and 3-hydroxymethylcarfentrazone-chloropropionic acid (HM-C-CI-PAc). The major animal metabolites are carfentrazone-chloropropionic acid (C-CI-PAc) and carfentrazone-propionic acid (C-PAc). The tolerance expression for livestock and plant commodities is carfentrazone-ethyl plus the ester hydrolysis product, C-CI-PAc. 

In mammals and in the majority of bacteria, cobalamin regulates DNA synthesis indirectly through its effect on a step in folate metabolism, catalyzing the synthesis of methionine from homocysteine and 5-methyltetrahydrofolate via two methyl transfer reactions. This cytoplasmic reaction is catalyzed by methionine synthase (5-methyltetrahydrofolate-homocysteine methyl-transferase), which requires methyl cobalamin (MeCbl) (253), one of the two known coenzyme forms of the complex, as its cofactor. 5 -Deoxyadenosyl cobalamin (AdoCbl) (254), the other coenzyme form of cobalamin, occurs within mitochondria. This compound is a cofactor for the enzyme methylmalonyl-CoA mutase, which is responsible for the conversion of T-methylmalonyl CoA to succinyl CoA. This reaction is involved in the metabolism of odd chain fatty acids via propionic acid, as well as amino acids isoleucine, methionine, threonine, and valine. 

Zmijewski, M., Gillespie, T.A., Jackson, D.A. etal. (2006) Application of biocatalysis to drug metabolism preparation of mammalian metabolites of a biaryl-bis-sulfonamide AMPA (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) receptor potentiator using Actinoplanes missouriensis. Drug Metabolism and Disposition The Biological Fate of Chemicals, 34, 925—931. 

Several mutant strains of R. eutropha that were made to possess defective competing metabolic pathways with the PHA biosynthetic pathway were developed for the enhanced PHA production. The isocitrate dehydrogenase leaky mutant of R. eutropha accumulated P(3HB) more favorably at a lower car-bon/nitrogen molar ratio and at a lower carbon concentration than the parent strain [82]. In batch culture, the final cell and P(3HB) concentrations, and P(3HB) yield on glucose were slightly increased. Also, in the P(3HB-co-3HV) biosynthesis, the molar fraction of 3HV and the 3HV yield on propionic acid increased due to the enhanced conversion of propionic acid to 3-hydroxyvaleryl-CoA rather than to acetyl-CoA and C02 in this mutant. Another mutant R. eu-... 

Valine, methionine, isoleucine, and threonine are all metabolized through the propionic acid pathway (also used for odd-carbon fatty acids). Defidency of either enzyme results in neonatal ketoacidosis from failure to metabolize ketoacids produced from these four amino adds. The defidendes may be distinguished based on whether meth)dmalonic adduria is present. A diet low in protein or a semisynthetic diet with low amounts of valine, methionine, isoleudne, and threonine is used to treat both deficiencies. 

An intriguing puzzle in NOS catalysis is the precise role of H4B. The traditional function of H4B is in aromatic amino acid metabolism where H4B directly participates in the hydroxylation reaction via a nonheme iron. However, the NOS pterin site has no similarity to the pterin site in the hydroxylases, nor does NOS have a nonheme iron to assist pterin in substrate hydroxylation as in the amino acid hydroxylases 111). NOS more closely resembles pterin-containing enz5unes that have a redox function 81). In particular, N3 and the 03 amino group form H-bonds with either GIu or Asp residues in a series of pterin enzymes 112-116) similar to NOS, except that NOS utilizes the heme propionate (Fig. 6). 

Fig. 1. Metabolism of heme via bhiverdin to bilirubin. The abbreviations for the substituents throughout the figures are V, vinyl Pr, propionic acid.

This pathway is also important for ruminant animals, which are dependent on symbiotic microorganisms to break down their food. The microorganisms produce large amounts of propionic acid as a degradation product, which the host can channel into the metabolism in the way described. 

Propionic acid does not appear to be geno-toxic. In vitro mutagenicity assays with propionic acid, using Salmonella typhimurium or Saccharcmyces cerevisiae, were negative with or without metabolic activation. ... 

Flurbiprofen is a propionic acid derivative with a possibly more complex mechanism of action than other NSAIDs. Its (S)( ) enantiomer inhibits COX nonselectively, but it has been shown in rat tissue to also affect tumor necrosis factor- (TNF- ) and nitric oxide synthesis. Flepatic metabolism is extensive its (R) +) and (S) ) enantiomers are metabolized differently, and it does not undergo chiral conversion. It does demonstrate enterohepatic circulation. 

Lenton WA, Gravel RA, Rosenblatt DS (2001) Disorders of propionate and methylmalonic acid metabolism. In Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The Metabolic and Molecular Bases of Inherited Disease, 8th edn. McGraw-Hill, New York, NY, pp 2165-2193... 

The oxidation of aciy lic acid can be rationalized in terms of the endogenous catabolism of propionic acid, in which acrylyl coenzyme A is an intermediate. This pathway is analogous with fatty acid 3-oxidation, common to all species and, unlike the corresponding pathway in plants, does not involve vitamin 8,2. 3-Hydroxypropionic acid has been found as an intennediate in the metabolism of acrylic acid in vitro in rat liver and mitochondria (Finch Frederick, 1992). The CO2 excreted derives from the carboxyl carbon, while carbon atoms 2 and 3 are converted to acetyl coenzyme A, which participates in a variety of reactions. The oxidation of acrylic acid is catalysed by enzymes in a variety of tissues (Black Finch, 1995). In mice, the greatest activity was found in kidney, which was five times more active than liver and 50 times more active than skin (Black et al., 1993). 

S. thermophilus metabolizes lactose to l( +) lactic acid but utilizes only the glucose moiety of lactose, leaving the galactose moiety in the cheese (Tinson et al. 1982). In Swiss cheese manufacture, S. thermophilus metabolizes the lactose and L. helveticus metabolizes the galactose to d( —) and l( + ) lactic acid (Turner et al. 1983). The l( + ) lactate isomer is preferentially utilized by propionibacteria to form acetic and propionic acids, which are essential for the development of the characteristic flavor in Swiss cheese (Langsrud and Reinbold 1973). 

Figure 13.7 Metabolic pathway for production of propionic acid by propi-onibacteria.

Hettinga, D. H. and Reinbold, G. W. 1972B. The propionic-acid bacteria—A review. II. Metabolism. J. Milk Food Technol. 35, 358-372. 

The production of substances that preserve the food from contamination or from oxidation is another important field of membrane bioreactor. For example, the production of high amounts of propionic acid, commonly used as antifungal substance, was carried out by a continuous stirred-tank reactor associated with ultrafiltration cell recycle and a nanofiltration membrane [51] or the production of gluconic acid by the use of glucose oxidase in a bioreactor using P E S membranes [52]. Lactic acid is widely used as an acidulant, flavor additive, and preservative in the food, pharmaceutical, leather, and textile industries. As an intermediate product in mammalian metabolism, L( +) lactic acid is more important in the food industry than the D(—) isomer. The performance of an improved fermentation system, that is, a membrane cell-recycle bioreactors MCRB was studied [53, 54], the maximum productivity of 31.5 g/Lh was recorded, 10 times greater than the counterpart of the batch-fed fermentation [54]. 

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