Control Mechanisms in the Synthesis of Saturated Fatty Acids

Bloch, Konrad E.; Vance, Dennis E.

doi:10.1146/annurev.bi.46.070177.001403

Cited by 319 publications

(149 citation statements)

References 80 publications

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“…Knowledge concerning the genes and enzymes of DNL and their regulation has advanced considerably (reviewed in Bloch, 1977;Girard et al, 1994;Sul et al, 1993). Nevertheless, quantitative and regulatory aspects of DNL in metabolic physiology remain controversial.…”

Section: Background and Historical Reviewmentioning

confidence: 99%

“…28% of the energy content of CHO, Flatt, 1978;Hellerstein et al, 1996), the pathway is known to have regulated steps and is therefore presumed to play a role in normal physiology. Despite considerable information about the regulation of acetyl-CoA carboxylase, fatty acyl synthetase, malonyl-CoA and other components of the enzymatic pathway (Bloch, 1977;Girard et al, 1994), the quantitative importance of DNL has remained an area of uncertainty until recently.…”

Section: Background and Historical Reviewmentioning

confidence: 99%

“…The ®rst committed step in the lipogenic pathway is synthesis of malonyl-CoA from acetyl-CoA and carbon dioxide, catalyzed by the enzyme acetyl-CoA carboxylase (Bloch, 1977;Girard et al, 1994). Malonyl-CoA inhibits transport of FA-CoAs into mitochondria by inhibiting carnitine acyl-transferase I activity (McGarry & Foster, 1980).…”

Section: What Is the Contribution Of Adipose Dnl In Humans?mentioning

confidence: 99%

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De novo lipogenesis in humans: metabolic and regulatory aspects

1999

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The enzymatic pathway for converting dietary carbohydrate (CHO) into fat, or de novo lipogenesis (DNL), is present in humans, whereas the capacity to convert fats into CHO does not exist. Here, the quantitative importance of DNL in humans is reviewed, focusing on the response to increased intake of dietary CHO. Eucaloric replacement of dietary fat by CHO does not induce hepatic DNL to any substantial degree. Similarly, addition of CHO to a mixed diet does not increase hepatic DNL to quantitatively important levels, as long as CHO energy intake remains less than total energy expenditure (TEE). Instead, dietary CHO replaces fat in the whole-body fuel mixture, even in the post-absorptive state. Body fat is thereby accrued, but the pathway of DNL is not traversed; instead, a coordinated set of metabolic adaptations, including resistance of hepatic glucose production to suppression by insulin, occurs that allows CHO oxidation to increase and match CHO intake. Only when CHO energy intake exceeds TEE does DNL in liver or adipose tissue contribute signi®cantly to the wholebody energy economy. It is concluded that DNL is not the pathway of ®rst resort for added dietary CHO, in humans. Under most dietary conditions, the two major macronutrient energy sources (CHO and fat) are therefore not interconvertible currencies; CHO and fat have independent, though interacting, economies and independent regulation. The metabolic mechanisms and physiologic implications of the functional block between CHO and fat in humans are discussed, but require further investigation. IntroductionIn this review, I will address the fate of surplus dietary carbohydrate (CHO) in humans. More speci®cally, the focus will be on conversion of CHO to fat, or de novo lipogenesis (DNL), with the question framed in quantitative terms: to what extent is surplus dietary CHO energy converted to fat? The various ways in which CHO content of the diet can be increased will be considered: increased CHO that replaces dietary fat (high-CHO low-fat, eucaloric diets); CHO added to a mixed diet, where CHO energy is less than total energy expenditure (TEE) but total energy intake exceeds TEE; and CHO consumption in excess of TEE. This review will therefore focus on the upper limits and consequences of increased CHO intake rather than on the lower limits and consequences of insuf®cient fat intake. Background and historical review

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Section: Background and Historical Reviewmentioning

confidence: 99%

Section: Background and Historical Reviewmentioning

confidence: 99%

Section: What Is the Contribution Of Adipose Dnl In Humans?mentioning

confidence: 99%

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De novo lipogenesis in humans: metabolic and regulatory aspects

1999

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“…The mechanism involves the sequential condensation of 3 molecules of malonyl-CoA with 1 molecule of 4-coumaroyl-CoA [l-3] . The condensation reaction is inhibited by cerulenin [l] , and should also in other respects bear a resemblance to the condensation reactions of fatty acid synthase [4] and 6-methylsalicylic acid synthase [5] . We have now obtained evidence for the occurrence of two characteristic side reactions, CO?…”

Section: Introductionmentioning

confidence: 99%

Flavanone synthase catalyzes CO₂ exchange and decarboxylation of malonyl‐CoA

Kreuzaler¹,

Light²,

Hahlbrock³

1978

FEBS Letters

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“…Acetyl-CoA carboxylase catalyses the rate-limiting step in fatty acid synthesis, and in mammals both the amount of the enzyme and its catalytic activity is regulated [1 ]. Short-term regulation is achieved either by variation in the levels of allosteric effectors or by reversible phosphorylation [2].…”

Section: Introductionmentioning

confidence: 99%

Regulation of mammalian acetyl‐CoA carboxylase

Guy¹,

Hardie²

1981

FEBS Letters

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Control Mechanisms in the Synthesis of Saturated Fatty Acids

Cited by 319 publications

References 80 publications

De novo lipogenesis in humans: metabolic and regulatory aspects

De novo lipogenesis in humans: metabolic and regulatory aspects

Flavanone synthase catalyzes CO₂ exchange and decarboxylation of malonyl‐CoA

Regulation of mammalian acetyl‐CoA carboxylase

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Control Mechanisms in the Synthesis of Saturated Fatty Acids

Cited by 319 publications

References 80 publications

De novo lipogenesis in humans: metabolic and regulatory aspects

De novo lipogenesis in humans: metabolic and regulatory aspects

Flavanone synthase catalyzes CO2 exchange and decarboxylation of malonyl‐CoA

Regulation of mammalian acetyl‐CoA carboxylase

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Flavanone synthase catalyzes CO₂ exchange and decarboxylation of malonyl‐CoA