Identity of heart and liver l-3-hydroxyacyl coenzyme A dehydrogenase

He, Xue Ying; Zhang, Guolong; Blecha, Frank; Yang, Song

doi:10.1016/s1388-1981(98)00005-5

Cited by 18 publications

(18 citation statements)

References 19 publications

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“…The penultimate step of the mitochondrial FAO cycle is catalyzed by 3‐hydroxyacyl‐CoA dehydrogenase (HAD; EC 1.1.1.35) [7–13] and a membrane‐associated long chain 3‐hydroxyacyl‐CoA dehydrogenase (LCHAD) [14–18], and is also catalyzed by short chain 3‐hydroxyacyl‐CoA dehydrogenase (SCHAD) [19–22](Table 1). The latter enzyme, with a preference for short chain rather than long chain 3‐hydroxy‐2‐methylacyl‐CoA, was first purified from rat liver [20] and then cloned from human brain [19].…”

Section: Introductionmentioning

confidence: 99%

3‐Hydroxyacyl‐CoA dehydrogenase and short chain 3‐hydroxyacyl‐CoA dehydrogenase in human health and disease

Yang

Schulz

2005

The FEBS Journal

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3‐Hydroxyacyl‐CoA dehydrogenase (HAD) functions in mitochondrial fatty acid β‐oxidation by catalyzing the oxidation of straight chain 3‐hydroxyacyl‐CoAs. HAD has a preference for medium chain substrates, whereas short chain 3‐hydroxyacyl‐CoA dehydrogenase (SCHAD) acts on a wide spectrum of substrates, including steroids, cholic acids, and fatty acids, with a preference for short chain methyl‐branched acyl‐CoAs. Therefore, HAD should not be referred to as SCHAD. SCHAD is not a member of the HAD family, but instead, belongs to the short chain dehydrogenase/reductase superfamily. Previously reported cases of SCHAD deficiency are due to an inherited HAD deficiency. SCHAD, also known as 17β‐hydroxysteroid dehydrogenase type 10, is important in brain development and aging. Abnormal levels of SCHAD in certain brain regions may contribute to the pathogenesis of some neural disorders. The human SCHAD gene and its protein product, SCHAD, are potential targets for intervention in conditions, such as Alzheimer's disease, Parkinson's disease, and an X‐linked mental retardation, that may arise from the impaired degradation of branched chain fatty acid and isoleucine.

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Section: Introductionmentioning

confidence: 99%

3‐Hydroxyacyl‐CoA dehydrogenase and short chain 3‐hydroxyacyl‐CoA dehydrogenase in human health and disease

Yang

Schulz

2005

The FEBS Journal

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“…The primary structure of its subunit is identical to that of an amyloid β-peptide-binding protein reportedly associated with the endoplasmic reticulum (endoplasmic-reticulum-associated amyloid β-peptide-binding protein, ERAB) [1,2]. SCHAD is capable of catalysing the third reaction of the fatty acid β-oxidation spiral [1], and in that respect is similar to the classic -3-hydroxyacyl-CoA dehydrogenase (-3-HAD) [3,4], although the latter is a two-domain dehydrogenase whereas human SCHAD is a single-domain dehydrogenase [1,5]. We have demonstrated that the human SCHAD gene product is a multifunctional enzyme, which is transported into mitochondria and functions in two different pathways of lipid metabolism [6].…”

Section: Introductionmentioning

confidence: 99%

Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase

Yang

Schulz

et al. 1999

Biochemical Journal

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The alcohol dehydrogenase (ADH) activity of human shortchain -3-hydroxyacyl-CoA dehydrogenase (SCHAD) has been characterized kinetically. The k cat of the purified enzyme was estimated to be 2.2 min −" , with apparent K m values of 280 mM and 22µM for 2-propanol and NAD + , respectively. The k cat of the ADH activity was three orders of magnitude less than the -3-hydroxyacyl-CoA dehydrogenase activity but was comparable with that of the enzyme's hydroxysteroid dehydrogenase (HSD) activity for oxidizing 17β-oestradiol [He, Merz, Mehta, Schulz and Yang (1999)

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“…The primary structure of this L-3-hydroxyacyl-CoA dehydrogenase is identical to an amyloid ␤-peptide-binding protein called endoplasmic reticulum-associated-binding protein (ERAB) (1)(2)(3). Human short chain L-3-hydroxyacyl-CoA dehydrogenase has a molecular mass of 108 kDa, and its structure is quite distinct from other L-3-hydroxyacyl-CoA dehydrogenases that bear the signature pattern of the L-3-hydroxyacylCoA dehydrogenase family (4,5). Although this enzyme is not homologous to the classic L-3-hydroxyacyl-CoA dehydrogenase (L-3-HAD), which is encoded by the human HADHSC gene located at chromosome 4q22-26 (6), functional convergence during evolution has conferred on them the capability of catalyzing the same reaction: L-3-hydroxyacyl-CoA ϩ NAD ϩ º 3-ketoacyl-CoA ϩ NADH ϩ H ϩ (1).…”

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Human Brain Short Chain l-3-Hydroxyacyl Coenzyme A Dehydrogenase Is a Single-domain Multifunctional Enzyme

He¹,

Merz²,

Mehta³

et al. 1999

Journal of Biological Chemistry

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Human brain short chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) was found to catalyze the oxidation of 17␤-estradiol and dihydroandrosterone as well as alcohols. Mitochondria have been demonstrated to be the proper location of this NAD ؉ -dependent dehydrogenase in cells, although its primary structure is identical to an amyloid ␤-peptide binding protein reportedly associated with the endoplasmic reticulum (ERAB). This fatty acid ␤-oxidation enzyme was identified as a novel 17␤-hydroxysteroid dehydrogenase responsible for the inactivation of sex steroid hormones. The catalytic rate constant of the purified enzyme was estimated to be 0.66 min ؊1 with apparent K m values of 43 and 50 M for 17␤-estradiol and NAD ؉ , respectively. The catalytic efficiency of this enzyme for the oxidation of 17␤-estradiol was comparable with that of peroxisomal 17␤-hydroxysteroid dehydrogenase type 4. As a result, the human SCHAD gene product, a single-domain multifunctional enzyme, appears to function in two different pathways of lipid metabolism. Because the catalytic functions of human brain short chain L-3-hydroxyacyl-CoA dehydrogenase could weaken the protective effects of estrogen and generate aldehydes in neurons, it is proposed that a high concentration of this enzyme in brain is a potential risk factor for Alzheimer's disease.

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Identity of heart and liver l-3-hydroxyacyl coenzyme A dehydrogenase

Cited by 18 publications

References 19 publications

3‐Hydroxyacyl‐CoA dehydrogenase and short chain 3‐hydroxyacyl‐CoA dehydrogenase in human health and disease

3‐Hydroxyacyl‐CoA dehydrogenase and short chain 3‐hydroxyacyl‐CoA dehydrogenase in human health and disease

Intrinsic alcohol dehydrogenase and hydroxysteroid dehydrogenase activities of human mitochondrial short-chain L-3-hydroxyacyl-CoA dehydrogenase

Human Brain Short Chain l-3-Hydroxyacyl Coenzyme A Dehydrogenase Is a Single-domain Multifunctional Enzyme

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