Propionyl coenzyme

Roe CR, Millington DS, Maltby DA, Bohan TP, Hoppel CL (1984) L-carnitine enhances excretion of propionyl coenzyme A as propionylcarnitine in propionic acidemia. J Clin Invest 73 1785-1788... 

A multifunctional biosynthetic machinery mediates the synthesis of these complex natural products from acetyl- and propionyl-coenzyme A [3). In the case of type I polyketide-synthases, the )8-oxo-esters made by polycondcnsa-tion steps are modified for example by reduction or dehydration after the chain elongation. Additional specific enzymatic transformations, e.g. oxidations and glycosylations, usually take place after the decoupling at the completed macrocyclic ring framework [1,3],... 

The molecular backbone of the antibiotic erythromycin A [6-desoxy-erythronolide B (3)] is built up repetitively from one propionyl-coenzyme A (1) and six methyl-malonyl-coenzyme A (2) constituents by the action of polyketide-synthase, which itself consists of three proteins (DEBS 1 -3) (Schemes 1 and 2). Each protein contains two modules with several separate, cat-alytically active domains. In the first section, DEBS 1 carries an additional loading zone, and DEBS 3 contains a thioesterase in the final segment, catalyzing the decoupling of the product by building the lactone ring [6],... 

The method described is suitable for the assay of four biotin-containing carboxylases pyruvate carboxylase, acetyl-coenzyme A carboxylase, propionyl-coenzyme A carboxylase, and 3-methylcrotonyl-coenzyme A carboxylase. The assays do not require radioisotopes and are suitable for use in clinical laboratories. 

Substrates and products are separated by reversed-phase chromatography at 45°C on a Nucleosil Qs column (4.6 mm X 250 mm). For assay of acetyl-coenzyme A carboxylase, propionyl-coenzyme A carboxylase, and 3-methylcrotonyl-coenzyme A carboxylase, a linear gradient from solvent A (0.1 M sodium phosphate buffer, pH 2.1) to solvent B (methanol-solvent A, 80 20, v/v) was applied in 15 minutes at a flow rate of 1.5 mL/min. Quantitation was based on the absorbance of the product (malonyl-CoA, methylmalonyl-CoA, and 3-methylglutaconyl-CoA, respectively) at 260 nm. For assay of pyruvate carboxylase, pyruvate was separated by isocratic elution using 0.1 M sodium phosphate buffer (pH 2.1) containing 0.1 M sodium sulfate. Quantitation was based on the disappearance of pyruvate as followed at 210 nm. 

Odd-Chain Fatty Acids Yield Propionyl Coenzyme A in the Final Thiolysis Step... 

In addition to phenylacetonitrile and fluorene, various active methylene compounds such as indene, propiophenone, phenyl propionate, benzyl phenylacetate afforded the corresponding carboxylated products by the carboxylation reaction with La(0 Pr)3-Ph-N=C=0-C02 system. Of fundamental and practical importance is that S-benzyl thiopropionate was effectively carboxylated into a thioester of 2-methylmalonate in a good yield, since this reaction is related to the biological carboxylation of propionyl coenzyme A with a biotin enzyme. Other thioesters were also carboxylated similarly, where successful examples were thioesters of phenylacetic, acetic, and isovaleric acids carrying active methylene and methyne groups, respectively. 

Propionic acidaemia This is caused by deficiency of enzymes involved in the metabolism of propionyl coenzyme A... 

The oxidation of the side chain of 5j -cholestane-3a,7a,12a-triol to yield cholic acid or rather cholyl coenzyme A entails an co-oxidation followed by a jS-oxidation (Fig. 2). Early investigations (71,72) showed that the mitochondrial fraction of rat and mouse liver homogenate catalyzed the conversion of 5jS-cholestane-3a,7a, 12a-triol into 5/5-cholestane-3a,7a, 12a,26-tetrol and, when supplemented with the 100,000g supernatant fluid, the further transformation of 5j -cholestane-3a,7a,12a,26-tetrol into 3a,7a,12a-trihydroxy-5/9-cholestanoic acid (Fig. 2). Suld et al. (72) showed that the conversion of 3a,7a,12a-trihydroxy-5/5-cholestanoic acid into cholic acid (cholyl coenzyme A), catalyzed by the mitochondrial fraction fortified with the 100,000g supernatant fluid, occurs with the release of propionic acid (propionyl coenzyme A). 

Fig. 2. Conversion of 5/ -cholestane-3a,7a,12a-triol into cholyl coenzyme A. IX, 5)5-Cholestane-3a,7a,12a-triol X, 5 -cholestane-3a,7a,12a,26-tetrol XI, 3a,7a,12a-trihydroxy-5/5-cholestanoic acid XII, 3a,7a,12a-trihydroxy-5i3-choles-tanoyl coenzyme A XIII, 3a,7a,12a,24a-tetrahydroxy-5/5-cholestanoyl coenzyme A XIV, propionyl coenzyme A XV, cholyl coenzyme A.

Coude FX, Sweetman L, Nyhan WL. Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat Uver mitochondria. A possible explanation for hyperammonemia in propionic and methylmalonic acidemia. J Clin Invest. 1979 64(6) 1544-51. 

This and other information show that nine Cg units from malonyl-coenzyme A and one C3 unit from propionyl-coenzyme A condense to form the linear polyketide intermediate shown below. These units are joined by acylation reactions that are the biosynthetic equivalent of the malonic ester synthesis we studied in Section 18.7. These reactions are also similar to the acylation steps we saw in fatty acid biosynthesis (Special Topic E in WileyPLUS). Once formed, the linear polyketide cyclizes by enzymatic reactions akin to intramolecular aldol additions and dehydrations (Section 19.6). These steps form the tetracyclic core of akiavinone. Phenolic hydroxyl groups in akiavinone arise by enolization of ketone carbonyl groups present after the aldol condensation steps. Several other transformations ultimately lead to daunomycin ... 

Propionyl-coenzyme A, propionyl-CoA activated propionic acid, formed by attachment of coenzyme A to propionic acid by a thioester linkage. Pro-... 

Biotin serves as the prosthetic group of several enzymes that catalyse the transfer of carbon dioxide from one substrate to another. In animals there are three biotin-dependent enzymes of particular importance pyruvate carboxylase (carbohydrate synthesis from lactate), acetyl coenzyme A carboxylase (fatty acid synthesis) and propionyl coenzyme A carboxylase (the pathway of conversion of propionate to succinyl-CoA). The specific role of these enzymes in metabolism is discussed in Chapter 9. 

McAllister, H.C., and Coon. M.J., 1966. Further studies on the properties of liver propionyl coenzyme A holocarboxylase synthetase and the specificity of holocarboxylase formation. The Journal of Biological Chemistry. 241 2855-2861. 

Mildvan, a. S., Fung, C. H. and Feldman, R. J. (1975) Conformation of enzyme-bound propionyl coenzyme A determined by proton and phosphorous relaxation rates. Fed. Proc. 34,690. 

Odd-chain fatty acids are synthesised by many microorganisms, and are produced, but to a very limited extent, in animal tissues when the fatty acid synthetase accepts propionyl-coenzyme A as the primer moiecuie. 

Valentin HE, Mitsky TA, Mahadeo DA, Tran M, Gruys KJ (2000a) Application of a propionyl coenzyme A synthetase for poly(3-hydrQxypropionate-co-3-... 

---