Fatty acids oxoacids

If starvation lasts for more than 24 hours, the rate of degradation of body protein (process 2) exceeds the rate of protein synthesis (process 3). The resultant amino acids are converted to oxoacids, most of which are converted to glucose (process 6) which is released and used predominantly by the brain (see Chapter 6). In this condition, the ATP required for gluconeogenesis is obtained from the oxidation of fatty acids (Figure 8.14(b)). 

Scheme 23.4 Production of methylketones from fatty acids by Penicillium roqueforti. 1 ATP-de-pendent acylcoenzyme A (acyl-CoA) synthase 2 flavin adenine dinucleotidedependent acyl-CoA dehydrogenase 3 enoyl-CoA hydratase 4 NAD-dependent 3-hydroxyacyl-CoA dehydrogenase 5 3-oxoacyl-CoA thiolase 6 3-oxoacyl-CoA thiolester hydrolase and 3-oxoacid decarboxylase. (Adapted from [46])...

Polled hereford calves in Australia develop maple syrup urine disease relatively often/ 6 One cause was established as a mutation that introduces a stop codon that causes premature termination within the leader peptide during synthesis of the thiamin diphosphate-dependent El subunit. A similar biochemical defect in a mutant of Bacillus subtilis causes difficulties for this bacterium, which requires branched-chain fatty acids in its membranes. Branched acyl-CoA derivatives are needed as starter pieces for their synthesis (Chapter 29). With the oxidative decarboxylation of the necessary oxoacids blocked, the mutant is unable to grow unless supplemented with branched-chain fatty acids. 

The (R)-enzyme (molecular mass 800000) was shown to be identical with a subunit of the fatty acid synthase complex. It reduced 3-oxoacid esters specifically to (R)-hydroxyacid esters. K -values for ethyl 3-oxobutanoate and ethyl 3-oxohexanoate were determined as 17.0 mM and 2.0 mM, respectively. Intact fatty acid synthase showed no activity in catalyzing the reduction of 3-oxoacid esters. 

Oxoglutarate can also serve as a starter piece for elongation by the oxoacid pathway. Extension by three carbon atoms yields 2-oxosuberate (Eq. 21-1). This dicarboxylate is converted by reactions shown in Eq. 24-39 into biotin and in archaebacteria into the coenzyme 7-mercaptoheptanoylthreonine phosphate (HTP), Eq. 21-1. Lipoic acid is also synthesized from a fatty acid, the eight-carbon octanoate. A fatty acid synthase system that utilizes a mitochondrial ACP may have as its primary fimction the synthesis of ocfanoate for lipoic acid formation. The mechanism of insertion of the two sulfur atoms to form lipoate (Chapter 15) is imcerfain. If requires an iron-sulfur protein jg probably similar to the corresponding process in the synthesis of biotin (Eq. 24-39)9 93a formation of HTP (Eq. 21-1). One component of the archaebacterial cofactor methano-furan (Chapter 15) is a tetracarboxylic acid that is formed from 2-oxoglufarafe by successive condensations with two malonic acid imits as in fatty acid synthesis. ... 

The liver is clearly well equipped to utilize free fatty acids and to interconvert acetoacetate and hydroxybutyrate, but the virtual absence of 3-Oxoacid-CoA transferase and lipoprotein lipase means that any significant uptake of ketone bodies and triglycerides is restricted to extra-hepatic tissues. Heart and kidney contain the necessary enzymes to deal with all four fuels and this may reflect their high metabolic activity. Page and Williamson (1971) have shown that normal human brain has the capacity to utilize ketone bodies. 

Another important group of reactions are those in which the hydrocarbon chain of the alkoxyl radicals cleaves to form low molecular weight products, mainly volatile and sensory active compounds. The cleavage takes place on both sides of the alkoxyl radicals (Figure 3.45). The composition of reaction products formed from alkoxyl radicals derived from unsaturated fatty acids depends on which carbon, next to the hydroperoxide group, the double bond is located. In addition to non-volatile oxoacids and hydroxy acids. 

Acyl CoA synthetase synthesises, in the presence of HS-CoA, acyl-CoA from a saturated fatty acid. Acyl CoA is transformed by acyl-CoA dehydrogenase into 2,3-dehydroacyl-CoA, and isomerism leads to trhydroxyacyl dehydrogenase the latter compound is hydrolysed by 3-ketoacyl-CoA thiolase to HS-CoA and 3-oxoacid. This acid eliminates carbon dioxide and yields methylketone, with catalysis of decarboxylase. Reductase can reduce methylketone to a secondary alcohol. 

In barley grains, lipoxygenase has been well characterized and two isoenzymes have been purified [1-3] but the characterization of hydroperoxide-metabolizing enzymes has received less attention. Hydroperoxide-consuming enzymes can be divided into two types of enzymes. Hydroperoxide lyase cleaves fatty acid hydroperoxides into aldehydes and oxoacids, and hydroperoxide dehydrase (also named hydroperoxide isomerase) catalyzes the formation of a-and 7-ketols. 

Oxoacids (ketoacids) are less common than hydroxy acids. Saturated oxoacids with 10-24 carbon atoms and unsaturated oxoacids Fatty Melting point Fatty Melting point... 

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