Accession Number : AD1010627

Title :   The Metabolic Basis of Cystinosis

Descriptive Note : Technical Report

Corporate Author : Uniformed Services University Of The Health Sciences Bethesda United States

Personal Author(s) : Marcus,Susan B

Full Text :

Report Date : 12 May 1981

Pagination or Media Count : 65

Abstract : Cystinosis is a rare, recessively inherited disorder characterized by an intralysosomal accumulation of the disulfide amino acid cystine (Schulman, et al, 1967). Its metabolic basis has eluded precise delineation since its discovery in 1903 by Abderhalden. In its most severe form (nephropathic), it is present at birth, but symptomology does not appear until six months to one year of age. Affected children show glomerular damage usually progressing to death from uremia within the first decade of life. In the intermediate form, onset is by the second or third decade of life. The third type is completely benign, usually discovered only when a routine ophthalmologic examination reveals the characteristic cystine crystals in the cornea and conjunctiva. Matsuo and Greenberg (1958) purified an enzyme, gamma-cystathionase, isolated from rat liver which catalyzed both the deamination of homoserine and the cleavage of cystathionine. In the 1-homocysteinemethionine cycle, cystathionase plays a key role in the conversion of cystathionine to cysteine with alpha-ketobutyric acid and ammonia being side products. We postulate that under normal conditions, increased cyst(e)ine results in inhibition of the enzyme, the cycle then favoring formation of methionine. In cystinotic individuals, it is then postulated that there is a defect in this enzymethere is excessive cystine accumulation because cystathionase is not inhibited by its normal regulator, cystine. Activity of the enzyme was determined by the formation of aketobutyric acid (Friedemann and Haugen, 1943; Sayre and Greenberg, 1956), using either 1-cystathionine or 1-homoserine as substrate. In the presence of excess cystine, rat, monkey and human liver cystathionase was inhibited. Due to the rarity of cystinosis, it was not possible to obtain cystinotic liver samples for cystathionase determination at this time.

Descriptors :   metabolism , Cystine , enzymes , inhibition , substrates , liver , inhibitors , pathology , assaying , proteins , metabolic diseases

Distribution Statement : APPROVED FOR PUBLIC RELEASE