Oxidation in mitochondria

Although fatty acids are both oxidized to acetyl-CoA and synthesized from acetyl-CoA, fatty acid oxidation is not the simple reverse of fatty acid biosynthesis but an entirely different process taking place in a separate compartment of the cell. The separation of fatty acid oxidation in mitochondria from biosynthesis in the cytosol allows each process to be individually controlled and integrated with tissue requirements. Each step in fatty acid oxidation involves acyl-CoA derivatives catalyzed by separate enzymes, utihzes NAD and FAD as coenzymes, and generates ATP. It is an aerobic process, requiring the presence of oxygen. 

The enzymes in peroxisomes do not attack shorter-chain fatty acids the P-oxidation sequence ends at oc-tanoyl-CoA. Octanoyl and acetyl groups are both further oxidized in mitochondria. Another role of peroxisomal P-oxidation is to shorten the side chain of cholesterol in bile acid formation (Chapter 26). Peroxisomes also take part in the synthesis of ether glycerolipids (Chapter 24), cholesterol, and dolichol (Figure 26-2). 

Fatty acid oxidation in mitochondria leads to the generation of large quantities of ATP by a process called P Oxidation that cleaves acetyl-CoA units sequentially from fatty acyl chains. The acetyl-CoA is oxidized in the citric acid cycle, generating further ATP. 

As it is similar to a fatty acid, it forms an acyl CoA and a carnitine derivative. This depletes CoA from the intramitochondrial pool and carnitine. Also, valproic acid is metabolized to an unsaturated fatty acid analogue, which is incorporated into p-oxidation in mitochondria. The reactive analogue depletes GSH and damages mitochondria. Function is compromised and ATP depleted. 

We begin this chapter with a brief discussion of the sources of fatty acids and the routes by which they travel to the site of their oxidation, with special emphasis on the process in vertebrates. We then describe the chemical steps of fatty acid oxidation in mitochondria The complete oxidation of fatty acids to C02 and H20 takes place in three stages the oxidation of long-chain fatty acids to two-carbon fragments, in the form of acetyl-CoA (/3 oxidation) the oxidation of acetyl-CoA to C02 in the citric acid cycle (Chapter 16) and the transfer of... 

Unsaturated fatty acids are also oxidized in mitochondria with the help of certain additional enzymes that facilitate a continuous flow of the oxidation process. 

A model reaction of oxidation in mitochondria has been proposed using a stable — 2/—1 redox couple of the bulky thiolate-containing model complexes. Figure 18 shows the scheme of the catalytic oxidation of benzil by benzoquinone in the presence of Fe4S42+ complexes (63). Thecomplex [Fe4S4(Z-cys-Ile-Ala-OMe)4]2, which hasastable —2/ —1 redox couple at +0.12 V versus SCE in DMF, exhibits a high catalytic activity (54). 

Eugene Kennedy and Albert Lehninger showed in 1949 that fatty acids are oxidized in mitochondria. Subsequent work demonstrated that they are activated before they enter the mitochondrial matrix. Adenosine triphosphate (ATP) drives the formation of a thioester linkage between the carboxyl group of a fatty acid and the sulfhydryl group of CoA. This activation reaction takes place on the outer mitochondrial membrane, where it is catalyzed by acyl CoA synthetase (also called fatty acid thiokinase). 

Lysine is formed in bacteria by decarboxylation of meso-diamino-pimelic acid (Fig. 24-14). Glycine is decarboxylated oxidatively in mitochondria in a sequence requiring lipoic acid and tetrahydrofolate as well as PLP (Fig. 15-20). A methionine decarboxylase has been isolated in pure form from a fem. ° The bacterial dialkylglycine decarboxylase is both a decarboxylase and an aminotransferase which uses pyruvate as its second substrate forming a ketone and L-alanine as products (See Eq. 

What are the differences between /5-oxidation in mitochondria and in peroxisomes What similarities are there between these processes ... 

Recall Is it fair to say that the synthesis of NADPH in chloroplasts is merely the reverse of NADH oxidation in mitochondria Explain your answer. 

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