Malonic aciduria

Medium-chain acyl CoA dehydrogenase deficiency 100% Malonic aciduria 92%... 

Nevertheless, malonyl-CoA is a major metabolite. It is an intermediate in fatty acid synthesis (see Fig. 17-12) and is formed in the peroxisomal P oxidation of odd chain-length dicarboxylic acids.703 Excess malonyl-CoA is decarboxylated in peroxisomes, and lack of the decarboxylase enzyme in mammals causes the lethal malonic aciduria.703 Some propionyl-CoA may also be metabolized by this pathway. The modified P oxidation sequence indicated on the left side of Fig. 17-3 is used in green plants and in many microorganisms. 3-Hydroxypropionyl-CoA is hydrolyzed to free P-hydroxypropionate, which is then oxidized to malonic semialdehyde and converted to acetyl-CoA by reactions that have not been completely described. Another possible pathway of propionate metabolism is the direct conversion to pyruvate via a oxidation into lactate, a mechanism that may be employed by some bacteria. Another route to lactate is through addition of water to acrylyl-CoA, the product of step a of Fig. 17-3. Tire water molecule adds in the "wrong way," the OH ion going to the a carbon instead of the P (Eq. 17-8). An enzyme with an active site similar to that of histidine ammonia-lyase (Eq. 14-48) could... 

CB 337 HMG) occurs free in Crotalaria dura and Crotalaria globifera. It is a biosynthesis precursor of isoprenoids, and is found in some cases of malonic aciduria. It has been used as an oral ANTIHYPERLIPIDAEMIC. 

Malonic aciduria is caused by a reduced activity of mitochondrial malo-nyl-CoA decarboxylase, the enzyme responsible for conversion of intramito-chondrial malonyl-CoA to acetyl-CoA. Hitherto, the disorder has been confined to nine patients. Clinical symptoms, which can develop soon after birth or in early childhood, include delayed neurological development, seizures, episodes of vomiting and anorexia, mild to severe metabolic acidosis and cardiomyopathy [12-15]. One patient died at the age of 8 days [15] the other patients are still alive, the oldest being 13 years of age. 

Matalon R, Michaels K, Kaul R et al. Malonic aciduria and cardiomyopathy. / Inher Metab Dis 1993 16 571-573... 

Buyukgebiz B, Jakobs C, Scholte HR, Huijmans JGM, Kleijer WJ. Fatal neonatal malonic aciduria. / Inher Metab Dis 1998 21 76-77... 

Malate/aspartate shuttle defect Malonic aciduria... 

Diagnosis may be made using gas chromatography alone (Gompertz et al, 1974), and this may be illustrated by reference to methylmalonic aciduria. Fig. 9.3 shows the chromatogram of amniotic fluid containing 9 tg of methyl-malonate ml as its methyl ester, obtained by ether extraction. Because of the possible confusion of methylmalonate with 3-hydroxybutyrate, a normal amniotic fluid constituent (Section 8.1), or 2-methyl-3-hydroxybutyrate, depending on the GC column used, these authors advised the use of mass... 

Fig. 10.1 Metabolites in the urine of an untreated patient with branched-chain keto aciduria (maple syrup urine disease). Extracted using ethyl acetate and separated as their trimethylsilyl-oxime derivatives on a 25 m SE-30 capillary column, using temperature programming from 80°C to 110°C at 0.5°C min and an injection split ratio 1 12 at a temperature of 250°C. The peaks marked R are due to solvent and reagents. Peak identifications are 1, lactic 2, 2-hydroxyisobutyric 3, 2-hydroxybutyric 4, pyruvic 5, 3-hydroxybutyric 6, 2-hydroxyisovaleric 7, 2-oxobutyric 8, 2-methyl-3-hydroxy-isovaleric 10, a and b, 2-oxoisovaleric 11, acetoacetic 12, 2-hydroxyisocaproic 13, 2-hydroxy-3-methyl- -valeric 14, 2-oxo-3-methyl-/i-valeric (14a L- 14b D-) 15, 2-oxoisocaproic acids. The internal standard was malonic acid. (Redrawn with modifications from Jellum etal., 1976)...

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