Abnormal Regulation of Plasma Pyridoxal 5'-Phosphate in Patients with Liver Disease

D. Mitchell, C. Wagner, W. J. Stone, G. R. Wilkinson, S. Schenker

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Pyridoxal 5'-phosphate (PLP), the coenzyme form of vitamin BI, is essential for many biochemical reactions in the body. Studies in experimental animals have suggested that the liver is a primary site for the formation of PLP circulating in the plasma, and that it may also participate in its degradation. This study evaluates, for the first time, the effects of liver disease in man on the regulation of plasma PLP. The plasma PLP level was measured before and sequentially after the rapid intravenous administration of 50 mg of pyridoxine to patients with alcoholic cirrhosis, acute hepatitis, and extrahepatic obstruction, and to normal control subjects. The base line plasma PLP concentration was significantly lower in cirrhotic patients than in normal persons (P < 0.025), and there was a tendency for it to be reduced in patients with extrahepatic obstruction. After administration of pyridoxine there was a significant increase in the plasma PLP level over a 2- to 12-hr period, after which the concentration returned gradually toward the initial value. The area under the concentration/time curve was from 2 to 8 times smaller (P < 0.002) in the patients with liver disease. To assess possible mechanisms of this change, 5 mg of PLP were intravenously administered to the various patient groups and the pharmacokinetics of the disposition were assessed. The initial and steady state volumes of distribution ofPLP were comparable in cirrhotics and controls (P > 0.05), but the clearance of plasma PLP in cirrhotics was much faster (63.0 ± 7.4 versus 31.7 ± 2.7 ml per min, P < 0.004). Similar findings were obtained in the other liver disease subjects. The in vitro plasma binding of PLP at supracirculatory concentrations was comparable in cirrhotics and controls (99.4 versus 99.5%, P > 0.05). In conclusion: (1) plasma PLP regulation in patients with liver disease is abnormal, (2) a significant factor in the decrease in plasma PLP after intravenous pyridoxine administration in these patients appears to be an increase in the total plasma clearance of the coenzyme, and (3) it is postulated that this may be due to increased degradation of PLP by the diseased liver.

Original languageEnglish (US)
Pages (from-to)1043-1049
Number of pages7
JournalGastroenterology
Volume71
Issue number6
DOIs
StatePublished - 1976
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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