Hepatic sulfur amino acid metabolism in rats with chronic renal failure.
We recently demonstrated elevated plasma amino acid concentrations and abnormal responses to amino acid supplementation (e.g., elevated methionine and phenylalanine) in children with chronic renal failure (CRF). We also recently developed an improved model of CRF in which animals manifest abnormal tissue amino acid levels, marked anorexia and growth failure. The objective of the current study was to determine the etiology of elevations of sulfur amino acids in animals with chronic renal failure. Chronic renal failure, defined as creatinine clearance less than 30% of control values, was induced in male rats in a two-stage surgical procedure. Four groups were studied over 2, 4 and 6 wk: control (non-operated) control (sham-operated), pair-fed (sham-operated and pair-fed with uremics) and CRF. Animals with CRF were anorexic and growth-retarded. Although plasma sulfur amino acid levels tended to be lower in the uremic animals than in controls, hepatic tissue concentrations were higher. Methionine adenosyltransferase was higher, but cystathione synthase and cystathionase activities were not significantly different in rats with CRF compared to pair-fed controls. We conclude that uremia, not malnutrition, affected sulfur amino acid metabolism and that with CRF, a normal adaptive response to elevated methionine levels was occurring, sufficient to normalize sulfur amino acid pool size. Alternative causes of elevated sulfur amino acids must be sought.
Bocock
M A
MA
Division of Clinical Nutrition, Hospital for Sick Children, Toronto, Ontario, Canada.
Zlotkin
S H
SH
D000603:Amino Acids, Sulfur / Q000378:metabolism*; D000818:Animals; D000855:Anorexia / Q000209:etiology; D003404:Creatinine / Q000097:blood / Q000652:urine; D003541:Cystathionine beta-Synthase / Q000032:analysis; D003542:Cystathionine gamma-Lyase / Q000032:analysis; D003553:Cystine / Q000378:metabolism; D004195:Disease Models, Animal; D006130:Growth Disorders / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008715:Methionine / Q000378:metabolism; D008716:Methionine Adenosyltransferase / Q000032:analysis; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D013654:Taurine / Q000378:metabolism; D014508:Urea / Q000097:blood; D014511:Uremia / Q000150:complications / Q000378:metabolism
D000603:Amino Acids, Sulfur; D013654:Taurine; D003553:Cystine; D014508:Urea; D008715:Methionine; D003404:Creatinine; D008716:Methionine Adenosyltransferase; D003541:Cystathionine beta-Synthase; D003542:Cystathionine gamma-Lyase