Liver acetyl CoA carboxylase and fatty acid synthetase: Relative activities in the normal state and in hereditary obesity

Chang, Huei-Che; Seidman, Irving; Teebor, George W.; Lane, M. Daniel

doi:10.1016/0006-291x(67)90369-5

Cited by 242 publications

(85 citation statements)

References 9 publications

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“…The supernatant cytosolic fractions were analysed for malic enzyme (ME, EC 1.1.1.40) and glucose-6-phosphate dehydrogenase (G6PDH, EC 1.1.1.49) using modifications [43] of the methods of Fitch et al [44] and Hsu and Lardy [45], respectively. Acetyl-CoA-carboxylase (ACC, EC 6.4.1.2) was assayed by the H 14 CO 3 -fixation method [46,47], using H 14 CO 3 (NEN, Life Science Product, Boston, USA, 49 mCi·mmol -1 ). ME and G6PDH activities were expressed as µmol of NADPH produced per min per total liver and mg of protein.…”

Section: Lipogenic Enzymesmentioning

confidence: 99%

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster

Morise¹,

Mourot²,

Riottot³

et al. 2005

Reprod. Nutr. Dev.

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-In order to meet dietary requirements, the consumption of α-linolenic acid (ALA, 18:3 n-3) must be promoted. However, its effects on triglyceride (TG) and cholesterol metabolism are still controversial, and may be dose-dependent. The effects of increasing dietary ALA intakes (1%, 10%, 20% and 40% of total FA) were investigated in male hamsters. ALA replaced oleic acid while linoleic and saturated FA were kept constant. Triglyceridemia decreased by 45% in response to 10% dietary ALA and was not affected by higher intakes. It was associated with lower hepatic total activities of acetyl-CoA-carboxylase (up to -29%) and malic enzyme (up to -42%), which were negatively correlated to ALA intake (r 2 = 0.33 and r 2 = 0.38, respectively). Adipose tissue lipogenesis was 2-6 fold lower than in the liver and was not affected by dietary treatment. Substitution of 10% ALA for oleic acid increased cholesterolemia by 15% but, as in TG, higher ALA intakes did not amplify the response. The highest ALA intake (40%) dramatically modified the hepatobiliary metabolism of sterols: cholesterol content fell by 45% in the liver and increased by 28% in the faeces. Besides, faecal bile acids decreased by 61%, and contained more hydrophobic and less secondary bile acids. Thus, replacing 10% oleic acid by ALA is sufficient to exert a beneficial hypotriglyceridemic effect, which may be counteracted by the slight increase in cholesterolemia. Higher intakes did not modify these parameters, but a very high dose resulted in adverse effects on sterol metabolism. α-linolenic acid / oleic acid / lipogenesis / cholesterol / triglyceride / bile acid / hamster

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Section: Lipogenic Enzymesmentioning

confidence: 99%

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster

Morise¹,

Mourot²,

Riottot³

et al. 2005

Reprod. Nutr. Dev.

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“…FAS activity in some muscle samples was found just below the detectable level of the assay, and thus FAS activity is not included in the data sets for LL muscle and the heart. ACC activity was determined by the H 14 CO 3 -fixation method using [1-14 C]acetate [21]. In the assay, ACC is maximally activated by citrate (provided in excess), using ATP and glutathion as cofactors, so the activity does not reflect the actual rate in vivo but represents the maximum potential of the enzyme under optimal conditions.…”

Section: Lipogenic Enzymesmentioning

confidence: 99%

Age-related relationships between muscle fat content and metabolic traits in growing rabbits

Gondret

Hocquette²,

Herpin³

2004

Reprod. Nutr. Dev.

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-This study was aimed at ascribing muscle fat accretion in growing rabbits to changes in several extra-muscular and intra-muscular metabolic pathways. At 10 wk or 20 wk of age (n = 8 per group), tissue lipid content and metabolic indicators of nutrient anabolic or catabolic pathways were simultaneously assessed in the liver, perirenal fat, the heart and the Longissimus lumborum (LL) muscle, together with plasma concentrations in energy-yielding metabolites. Lipid content significantly increased with age (P ≤ 0.01) in the glycolytic LL muscle (+67%) and the oxidative heart (+30%). In the former muscle, it was statistically correlated (r 2 = 0.68; P < 0.01) to the changes in the orientation of muscle metabolism towards an enhanced lipogenic capacity and a depressed capacity for fatty acid transport and nutrient oxidation, and to indications of lower availability in plasma glucose and triglycerides. In the heart, age-related fat accretion was positively associated (r 2 = 0.48, P < 0.01) to intrinsic metabolic changes towards an enhanced lipogenic capacity, together with a lower availability in plasma glucose. Variables representative of cardiac catabolic capacity tended to be negatively correlated to fat content in the heart (r 2 = 0.15, P = 0.07). In growing rabbits, muscle fat content variation was proven to result from a reciprocal balance between catabolic and anabolic fatty acid fluxes, rather than to be assigned to one specific energy metabolic pathway.

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“…This enzymic step was considered the rate-limiting step in the overall process of fatty acid biosynthesis [26]. However, recent work has shown that acetyl CoA carboxylase activity may not always be the limiting factor in the biosynthetic pathway [27,28]. I n this context, our demonstration that the fatty acid synthetase is inhibited dramatically by its end products assumes greater significance.…”

Section: Discussionmentioning

confidence: 91%

The Inhibition of the Fatty Acid Synthetase Multienzyme Complex of Yeast by Long‐Chain Acyl Coenzyme A Compounds

Lust

Lynen²

1968

European Journal of Biochemistry

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Fatty acid synthetase of yeast was strongly inhibited in vitro by long-chain acyl coenzyme A thioesters. Increasing the serum albumin concentration in the reaction mixture lowered, but did not prevent, this inhibition. Enzyme kinetic experiments showed that all long-chain acyl CoA compounds tested were competitive inhibitors of the substrate malonyl CoA. The inhibition with respect to the substrate acetyl CoA and NADPH was non-competitive. These results support the hypothesis put forth earlier that the end products of the fatty acid synthetase are bound preferentially in the region of the thiol group which is part of the acyl-carrier-protein portion of the complex. The data indicate that the long-chain acyl CoA thioesters may be of importance in the regulation of de novo fatty acid biosynthesis via end product inhibition of the synthetase.Long-chain acyl coenzyme A thioesters, the concentrations of which are increased during starvation [1,2] and diabetes [2], inhibit several individual reactions related to fatty acid biosynthesis as well as the overall process. For example, citrate was competitively inhibited by acyl CoA derivatives in the reaction catalyzed by acetyl coenzyme A carboxylase [3]. Palmityl CoA was shown to inhibit citrate-condensing enzyme [4,5] and to inhibit the rate of condensation of acetyl CoA and malonyl CoA as catalyzed by a purified rat brain enzyme [6]. Palmityl CoA also inhibited fatty acid synthesis catalyzed by pigeon liver enzymes [7], a crude rat liver fatty acid synthetase [2] and a cell-free preparation of yeast [8]. Furthermore, palmityl CoA inhibited glucose-6-phosphate dehydrogenase [9, lo], phosphatidic acid phosphatase [Ill, as well as a number of other enzymes not directly involved in lipogenesis [9].Previous work in this laboratory has shown that the activity of the fatty acid synthetase of yeast was markedly reduced when long-chain acyl CoA esters were used as substrates with malonyl CoA and NADPH [12,13]. To investigate this further, enzyme-kinetic studies of the inhibitory effect of saturated, long-chain acyl CoA compounds on the fatty acid synthetase were performed. The data suggest that regulation of de novo fatty acid biosynthesis may occur by means of end product inhibition of fatty acid synthetase.

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Liver acetyl CoA carboxylase and fatty acid synthetase: Relative activities in the normal state and in hereditary obesity

Cited by 242 publications

References 9 publications

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster

Dose effect of alpha-linolenic acid on lipid metabolism in the hamster

Age-related relationships between muscle fat content and metabolic traits in growing rabbits

The Inhibition of the Fatty Acid Synthetase Multienzyme Complex of Yeast by Long‐Chain Acyl Coenzyme A Compounds

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