OMIA:000853-9940 : Reduced glutathione deficiency due to GCS deficiency in Ovis aries (sheep)
Categories: Haematopoietic system phene
Possibly relevant human trait(s) and/or gene(s) (MIM number): 230450 (trait)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal
Considered a defect: yes
Key variant known: no
Cross-species summary: Glutathione is a small peptide consisting of just three amino acids: glutamic acid, cystein, and glycine. It is a widely-distributed molecule, serving as a reducing agent in many different metabolic processes. One of its most notable roles is in protecting red blood cells from oxidation and haemolysis. Glutathione normally exists in its reduced sulphydral form (GSH; often called reduced glutathione). Its oxidised form consists of two GSH molecules whose cysteines are joined by a di-sulphide bridge (symbolised GSSG). Unlike most peptides, glutathione is not the product of a gene; instead, it is manufactured from its three constituent amino acids in a two-step process catalysed by gamma-glutamylcysteine synthetase (GCS; which creates a di-peptide of glutamic acid and cysteine) and glutathione synthetase (GSHS; which adds glycine). Oxidation of GSH to GSSG is catalysed by glutathione peroxide (GPX); reduction back to GSH is catalysed by glutathione reductase (GR).
Species-specific description: In Merino sheep, a deficiency of GCS in red blood cells results in a deficiency of erythrocyte GSH but (unlike the situation in humans) no detectable anaemia or any other clinical signs, either chronically or after exposure to oxidant drugs. The deficiency is due to an allele at an autosomal locus, but there are conflicting data on whether the allele is recessive or dominant (Board and Agar, 1983).
Tasmanian Merino, Australia (Sheep) (VBO_0015629).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|1994||Bayon, Y., Arranz, J.J., Sanprimitivo, F. :|
|Red cell reduced glutathione concentrations in Spanish Churra sheep Animal Genetics 25:277-279, 1994. Pubmed reference: 7985845 .|
|1983||Agar, N.S., Young, J.D., Board, P.G. :|
|Erythrocyte amino acid and nucleoside transport :271-290, 1983.|
|Agar, N.S., Ellory, J.C., Board, P.G., Tucker, E.M. :|
|Cation transport in red blood cells :291-314, 1983.|
|Board, P.G., Agar, N.S. :|
|Glutathione metabolism in erythrocytes :253-270, 1983.|
|Tucker, E.M., Kilgour, L., Crowley, C., Young, J.D. :|
|Abnormal gamma-glutamylcysteine synthetase activities in sheep red blood cells Biochemical Genetics 21:907-922, 1983. Pubmed reference: 6140916 .|
|1981||Atroshi, F., Osterberg, S., Lindstrom, U.B. :|
|The relationship between blood potassium and glutathione levels with carcass characteristics in Finnsheep Acta Agriculturae Scandinavica 31:87-90, 1981.|
|Tucker, E.M., Young, J.D., Crowley, C. :|
|Red cell glutathione deficiency. Clinical and biochemical investigations using sheep as an experimental model system British Journal of Haematology 48:403-, 1981. Pubmed reference: 6114741 .|
|1975||Young, J.D., Nimmo, I.A. :|
|GSH biosynthesis in glutathione deficient erythrocytes from Finnish Landrace and Tasmanian Merino Sheep Biochimica et Biophysica Acta 404:132-, 1975. Pubmed reference: 1174555 .|
|Young, J.D., Nimmo, I.A., Hall, J.G. :|
|The relationship between GSH, GSSG and non GSH thiol in GSH-deficient erythrocytes from Finnish Landrace and Tasmanian Merino sheep Biochimica et Biophysica Acta 404:124-, 1975. Pubmed reference: 1174554 .|
- Created by Frank Nicholas on 06 Sep 2005