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

Yang, Song‐Yu; He, Xue‐Ying; Schulz, Horst

doi:10.1111/j.1742-4658.2005.04911.x

Cited by 93 publications

(78 citation statements)

References 76 publications

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“…Indeed, both SDR5C1 and AKT are involved in the b-oxidation of isoleucine, where SRD5C1 catalyzes oxidation of 2-methyl-3-hydroxy-butyrate-CoA to 2-methyl-acetoacyl-CoA, and AKT catalyzes breakdown of 2-methyl-acetoacyl-CoA to propionylCoA and acetyl-CoA. 35 Because these 2 enzymes function in 2 consecutive steps of the same pathway, loss-of-function mutations in either enzyme show nearly identical urine organic acid profiles in patients. 36 This has led to misdiagnosis of the more severe clinical disorder caused by SRD5C1 deficiency as AKT deficiency.…”

Section: Discussionmentioning

confidence: 99%

A novelHSD17B10mutation impairing the activities of the mitochondrial RNase P complex causes X-linked intractable epilepsy and neurodevelopmental regression

et al. 2016

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(2016) A novel HSD17B10 mutation impairing the activities of the mitochondrial RNase P complex causes X-linked intractable epilepsy and neurodevelopmental regression, RNA Biology, 13:5, 477-485, DOI: 10.1080/15476286.2016 ABSTRACTWe report a Caucasian boy with intractable epilepsy and global developmental delay. Whole-exome sequencing identified the likely genetic etiology as a novel p.K212E mutation in the X-linked gene HSD17B10 for mitochondrial short-chain dehydrogenase/reductase SDR5C1. Mutations in HSD17B10 cause the HSD10 disease, traditionally classified as a metabolic disorder due to the role of SDR5C1 in fatty and amino acid metabolism. However, SDR5C1 is also an essential subunit of human mitochondrial RNase P, the enzyme responsible for 5 0 -processing and methylation of purine-9 of mitochondrial tRNAs. Here we show that the p.K212E mutation impairs the SDR5C1-dependent mitochondrial RNase P activities, and suggest that the pathogenicity of p.K212E is due to a general mitochondrial dysfunction caused by reduction in SDR5C1-dependent maturation of mitochondrial tRNAs.

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Section: Discussionmentioning

confidence: 99%

A novelHSD17B10mutation impairing the activities of the mitochondrial RNase P complex causes X-linked intractable epilepsy and neurodevelopmental regression

et al. 2016

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“…This protein was also identified in spot A corresponding to the full protein. Downregulation of histidine triad nucleotide-binding protein 1 (Hint1; spot B), an enzyme able to hydrolyze adenosine 5 0 -monophosphoramidate substrates [41], of oeroxiredoxin 6 (spot H), and of 3-hydroxyacyl-CoA dehydrogenase (spot J) functioning in mitochondrial transfer RNA maturation, were also observed [42].…”

Section: Proteomic Profiles Of Control and Gold-treated Cancer Cellsmentioning

confidence: 99%

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

et al. 2010

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We have recently shown that a group of structurally diverse gold compounds are highly cytotoxic toward a panel of 36 human tumor cell lines through a variety of biochemical mechanisms. A classic proteomic approach is exploited here to gain deeper insight into those mechanisms. This investigation is focused on Auoxo6, a novel binuclear gold(III) complex, and auranofin, a clinically established gold(I) antiarthritic drug. First, the 72-h cytotoxicity profiles of Auoxo6 and auranofin were determined against A2780 human ovarian carcinoma cells. Subsequently, protein extraction from gold-treated A2780 cells sensitive to cisplatin and 2D gel electrophoresis separation were carried out according to established procedures. Notably, both metallodrugs caused relatively modest changes in protein expression in comparison with controls as only 11 out of approximately 1,300 monitored spots showed appreciable quantitative changes. Very remarkably, six altered proteins were in common between the two treatments. Eight altered proteins were identified by mass spectrometry; among them was ezrin, a protein associated with the cytoskeleton and involved in apoptosis. Interestingly, two altered proteins, i.e., peroxiredoxins 1 and 6, are known to play crucial roles in the cell redox metabolism. Increased cleavage of heterogeneous ribonucleoprotein H was also evidenced, consistent with caspase 3 activation. Overall, the results of the present proteomic study point out that the mode of action of Auoxo6 is strictly related to that of auranofin, that the induced changes in protein expression are limited and selective, that both gold compounds trigger caspase 3 activation and apoptosis, and that a few affected proteins are primarily involved in cell redox homeostasis.

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“…It also exhibits short-chain 3-hydroxy-2-methylacylCoA dehydrogenase activity such that it is essential for the degradation of isoleucine (7)(8)(9). This dehydrogenase is encoded by the HSD17B10 gene (formerly the HADH2 gene) that maps to chromosome Xp11.2 (OMIM300256) (10).…”

mentioning

confidence: 99%

“…These two consecutive catabolic steps are catalyzed by HSD10 (EC 1.1.1.178/35/239/159/150) (8) and mitochondrial acetoacetyl-CoA thiolase (␤-ketothiolase, EC 2.3.1.9) (13), respectively. The latter enzyme is encoded by the ACAT1 gene (OMIM607809).…”

mentioning

confidence: 99%

Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism

Yang¹,

He²,

Olpin

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Mutations in the HSD17B10 gene were identified in two previously described mentally retarded males. A point mutation c.776G>C was found from a survivor (SV), whereas a potent mutation, c.419C>T, was identified in another deceased case (SF) with undetectable hydroxysteroid (17␤) dehydrogenase 10 (HSD10) activity. Protein levels of mutant HSD10(R130C) in patient SF and HSD10(E249Q) in patient SV were about half that of HSD10 in normal controls. The E249Q mutation appears to affect HSD10 subunit interactions, resulting in an allosteric regulatory enzyme. For catalyzing the oxidation of allopregnanolone by NAD ؉ the Hill coefficient of the mutant enzyme is Ϸ1.3. HSD10(E249Q) was unable to catalyze the dehydrogenation of 2-methyl-3-hydroxybutyryl-CoA and the oxidation of allopregnanolone, a positive modulator of the ␥-aminobutyric acid type A receptor, at low substrate concentrations. Neurosteroid homeostasis is critical for normal cognitive development, and there is increasing evidence that a blockade of isoleucine catabolism alone does not commonly cause developmental disabilities. The results support the theory that an imbalance in neurosteroid metabolism could be a major cause of the neurological handicap associated with hydroxysteroid (17␤) dehydrogenase 10 deficiency.developmental disabilities ͉ HSD10 deficiency ͉ hydroxyacyl-CoA dehydrogenase

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

Cited by 93 publications

References 76 publications

A novelHSD17B10mutation impairing the activities of the mitochondrial RNase P complex causes X-linked intractable epilepsy and neurodevelopmental regression

A novelHSD17B10mutation impairing the activities of the mitochondrial RNase P complex causes X-linked intractable epilepsy and neurodevelopmental regression

Exploring the biochemical mechanisms of cytotoxic gold compounds: a proteomic study

Mental retardation linked to mutations in the HSD17B10 gene interfering with neurosteroid and isoleucine metabolism

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