Vitamin B6 deficiency accelerates metabolic turnover of cystathionase in rat liver.
Although most of cystathionase was found to exist as an inactive apoenzyme in the liver of vitamin B6-deficient rats, the concentrations of the immunoreactive enzyme protein were virtually the same for control and vitamin B6-deficient livers. Under vitamin B6 deficiency, however, the rate of synthesis of cystathionase, measured by incorporation of labeled amino acid into the immunoprecipitated enzyme, was increased severalfold due to an increased level of cystathionase mRNA. Western blot analysis of lysosomal proteins showed that the amount of cystathionase in the lysosomes from the liver of vitamin B6-deficient rats was also increased severalfold. This observation suggests that lysosomes specifically recognize the apocystathionase for sequestration in preference to the holoenzyme. The present study provides the molecular basis for dual roles of vitamin B6 in controlling the metabolic turnover of cystathionase; it regulates synthesis of the enzyme by modulating the expression of cystathionase gene, and it regulates degradation of the enzyme by different susceptibilities of apo- and holoenzymes to lysosomal proteolysis.
Sato
A
A
Department of Food and Nutrition, Kochi Women's University, Kochi, Japan.
Nishioka
M
M
Awata
S
S
Nakayama
K
K
Okada
M
M
Horiuchi
S
S
Okabe
N
N
Sassa
T
T
Oka
T
T
Natori
Y
Y
D000818:Animals; D001051:Apoenzymes / Q000378:metabolism; D001483:Base Sequence; D003542:Cystathionine gamma-Lyase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015342:DNA Probes / Q000235:genetics; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D026681:Vitamin B 6 Deficiency / Q000201:enzymology*
D001051:Apoenzymes; D015342:DNA Probes; D012333:RNA, Messenger; D003542:Cystathionine gamma-Lyase