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Mechanism of fatty acid synthesis

1961; Elsevier BV; Volume: 2; Issue: 1 Linguagem: Inglês

10.1016/s0022-2275(20)39034-9

1539-7262

Salih J. Wakil,

Mitochondrial Function and Pathology

FATTY ACID SYNTHESIS 3tion cycle (thiolase, enoyl hydrase, and p-hydroxyacyl dehydrogenase), a source of DPNH (alcohol and alcohol dehydrogenase), and a source of TPNH (glucose-6-phosphate and glucose-6-phosphate dehydrogenase) .With this system they were able to demonstrate the synthesis of octanoyl and capryl CoA from hexanoyl CoA and a ~e t y 1 -l -C ~~ CoA.However, the poor yield of naturally occurring longer chain fatty acids, e.g., stearic and palmitic, suggested that this pathway for fatty acid synthesis may not be the operational one in vivo.Stumpf and Barber (18) were the first to show the fatty acid synthesis in intact mitochondria derived from avocado mesocarp.Adenosine triphosphate, CoA, and Mn++ were essential components for the conversion of C14-acetate into the long-chain fatty acids (palmitic and oleic) in this system.Recently, Wakil et al. ( 19) were able to demonstrate that intact mitochondria isolated from pigeon, rat, or beef livers can synthesize long-chain fatty acids from acetyl CoA (Table 1 ) .Mitochondria were pre-TABLE 1. FATTY ACID SYNTHESIS BY MITOCHONDRIA I Acetyl CoA Incorporated into Long-chain Fatty Acids Complete system* No ATP No TPNH No DPNH No TPNH; no DPNH Complete system + HCOi No acetyl CoA + malonyl CoA No acetyl CoA + malonyl CoA, without ATP p m l e s 4.5 0.3 2.4 2.0 0.0 3.0 2.4 0.8 ~ * The reaction mixture contained 34.5 mpmoles acetyl CoA (55,200 cpm), 8 pmoles ATP, 0.25 pmole TPNH, 0.25 pmole DPNH, 2.8 mg of mitochondrial protein, 50 pmoles phosphate (pH 6.5), and H,O to a total volume of 0.5 ml.Four pmoles KHCOa and 30 mpmoles malonyl CoA (HOOC CH2C"O CoA 70,000 cpm) were used where indicated.The reaction mixture was incubated anaerobically a t 38' for 1 hour.