Content of Sulfur Amino Acids and Vitamin B₆ and Related Enzyme Activities in Rats with Chronic Renal Failure Fed a High Methionine Diet

Abstract

The effect of concentrations of sulfur-containing amino acids, activities of cys-tathionine n-lyase and cystathionine β-synthase, and level of vitamin B₆ were examined following menthionine adminstration in normal rats and chronically uremic rats with 7/8 nephrectomy. In the uremic rats, the serum levels of methionine, cystathionine, cysteine and taurine increased in proportion to the amounts of methionine administered. The increase of taurine content in the serum and liver was particularly marked. Cystathionine β-synthase activity in the liver increased with the administration, but the serum level of pyridoxal phosphate decreased markedly. The body weight gain of rats decreased with the administration, and the contents of urea and creatinine in serum increased. Thus, vitamin B6 deficiency in chronically uremic rats administered with large amounts of methionine may reduce growth, lower renal function and cause abnormal metabolism of sulfur-containing amino acids.

No net renal extraction of homocysteine in fasting humans

“…One might also speculate that extrarenal homocysteine metabolism is impaired by factors related to uremia per se such as accumulation of uremic toxins, which could inhibit homocysteine metabolizing enzymes, interfere with the metabolism of folic acid [26], or impair folic acid transmembrane transport [27]. The major candidate site for extarenal homocysteine metabolism is the liver, in which extensive amino acid and protein metabolism takes place, and in which many abnormalities of amino acid metabolism have been described in renal failure, including those of sulfur-containing amino acids [28,29].…”

Elevated Levels of Serum Sulfite in Patients with Chronic Renal Failure

“…It is also possible that enzyme activity of sulfite oxidase is impaired in CRF patients. In addition, metabolism of sulfur-containing amino acids such as methionine, cysteine, and homocysteine has been reported to be aberrant in CRF patients (23,24). Because sulfite is an intermediary metabolite in the normal processing of these amino acids (4,5), this may be an alternative mechanism by which serum sulfite is elevated in CRF patients.…”

Blood sulfur-amino acid concentration reflects an impairment of liver transsulfuration pathway in patients with acute abdominal inflammatory processes

“…Previous studies of S-amino acid metabolism during stress have been carried out on animals, so our aim was to determine if it was possible to detect an indication of the inhibition of liver g-cystathionase in the whole blood of human subjects in stressful conditions, particularly as it is known that the activity in human liver is only one-fifth of that present in rat liver (Zlotkin & Anderson 1982;Rao et al 1990). It is interesting to point out that the activity of human liver cystathionine b-synthase, the other enzyme of the transsulfuration pathway, is also one-fifth of that present in rat liver (Kraus & Rosenberg 1983;Asagi et al 1996). In rats, 50 % rat liver g-cystathionase activity appears to be sufficient for transsulfuration, but 50 % of the human adult level of hepatic g-cystathionase may not be sufficient (Rao et al 1990); therefore, a slight inhibition of the enzyme may change the blood S-amino acid pattern in man and could be a useful test which reflects the impairment of the transsulfuration pathway.…”