OMIA 000853-9940 : Reduced glutathione deficiency due to GCS deficiency in Ovis aries

Possibly relevant human trait(s) and/or gene(s) (MIM number): 230450

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).

Breed: Tasmanian Merino.

References


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., Ellory, J.C., Board, P.G., Tucker, E.M. :
Cation transport in red blood cells :291-314, 1983.
Agar, N.S., Young, J.D., Board, P.G. :
Erythrocyte amino acid and nucleoside transport :271-290, 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.

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  • Created by Frank Nicholas on 06 Sep 2005