Disease relevance of HADH

• Previously, it has been shown that mutations in the corresponding gene (HADHSC) are associated with hyperinsulinism in infancy [1].
• Familial hyperinsulinemic hypoglycemia caused by a defect in the SCHAD enzyme of mitochondrial fatty acid oxidation [2].
• We propose that inhibitors of the 3alpha-HSD activity of human brain SCHAD could be useful for the treatment of benign prostatic hyperplasia and other disorders involving DHT metabolism, in combination with known inhibitors of steroid 5alpha-reductases [3].
• 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 [4].

Psychiatry related information on HADH

• 17Beta-HSD10/SCHAD mutations cause a spectrum of clinical conditions, from mild mental retardation to progressive infantile neurodegeneration [5].

High impact information on HADH

• Strikingly, one of these genes, Hadhsc, encodes short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase, deficiency of which has been shown to cause PHHI in humans [6].
• Sequencing of the short-chain L-3-hydroxyacyl-CoA dehydrogenase (SCHAD) genomic DNA from the fibroblasts showed a homozygous mutation (C773T) changing proline to leucine at amino acid 258 [7].
• The presumed function of the SCHAD enzyme in glucose-stimulated insulin secretion led us to the hypothesis that common variants in HADHSC on chromosome 4q22-26 might be associated with development of type 2 diabetes [1].
• The present study provides no evidence that the specific HADHSC variants or haplotypes examined do influence susceptibility to develop type 2 diabetes [1].
• Direct sequencing of HADHSC cDNA and databank analysis identified four tagging single nucleotide polymorphisms (SNPs) including one missense variant (P86L) [1].

Biological context of HADH

• By radiation hybrid panel, assisted fine-mapping HADHSC was linked to marker AFM070TH5, corresponding to Chromosome (Chr) 4q22-26, and a putative HADHSC pseudogene was linked to marker D15S1324, located at Chr 15q17-21 [8].
• The HADHSC 5'-flanking region was characterized with an AluI plasmid library constructed from a partially AluI-digested PAC clone containing the human HADHSC gene [8].
• Upon comparison with the HADHSC cDNA sequence, HADHSC was shown to encompass at least eight exons, ranging in size from 73 to 158 bp, and 7 introns [8].
• The deduced amino acid sequence of the mature protein shows a 92 percent identity with SCHAD from pig heart [9].
• Screening of a cDNA library combined with rapid amplification of 5' cDNA ends resulted in a SCHAD cDNA sequence of 1877 bp [9].

Anatomical context of HADH

• Western blot studies showed undetectable levels of immunoreactive SCHAD protein in the child's fibroblasts [7].
• Northern blot analysis reveals SCHAD mRNA to be expressed in liver, kidney, pancreas, heart and skeletal muscle [9].
• Human SCHAD is identical to an amyloid-beta binding protein (ERAB) involved in Alzheimer's disease, which was previously reported to be associated with the endoplasmic reticulum [3].
• According to the structure of the early-stage uterus, A. bairdi Schad, 1954 belongs to the genus Paranoplocephala [10].

Associations of HADH with chemical compounds

• Urine metabolite analysis showed that SCHAD deficiency resulted in specific excretion of 3-hydroxyglutaric acid [2].
• The crystal structure of SCHAD complexed with NAD+ has been solved using multiwavelength anomalous diffraction techniques and a selenomethionine-substituted analogue of the enzyme [11].
• Northern blot analysis revealed that the human SCHAD gene is expressed in both gonadal and peripheral tissues including the prostate whose growth notably requires DHT, the most potent androgen [3].
• SCHAD, also known as 17beta-hydroxysteroid dehydrogenase type 10, is important in brain development and aging [4].
• 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 [4].

Other interactions of HADH

• This report describes the clinical, biochemical, and pathological findings in three infants with hepatic short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase (SCHAD) deficiency, a recently recognized disorder of the mitochondrial oxidation of straight-chain fatty acids [12].

Analytical, diagnostic and therapeutic context of HADH

• The human SCHAD gene was mapped by fluorescence in situ hybridization to chromosome 4q22-26 [9].
• Here, David Pritchard, Paul McKean and Gerry Schad describe some aspects of the comparative biochemistry of Necator americanus and Ancylostoma duodenale, and emphasize differences between the species that could form the basis of discriminatory diagnostic tests [13].

References