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  • Title: Ontogeny of carnitine biosynthesis in Sus scrofa domesticus, inferred from γ-butyrobetaine hydroxylase (dioxygenase) activity and substrate inhibition.
    Author: Lin X, Lyvers Peffer PA, Woodworth J, Odle J.
    Journal: Am J Physiol Regul Integr Comp Physiol; 2020 Jul 01; 319(1):R43-R49. PubMed ID: 32432915.
    Abstract:
    γ-Butyrobetaine hydroxylase (γ-BBH) is the last limiting enzyme of the l-carnitine biosynthesis pathway and plays an important role in catalyzing the hydroxylation of γ-butyrobetaine (γ-BB) to l-carnitine. To study the developmental effect of substrate concentration on the enzyme's specific activity, kinetics of γ-BBH were measured in liver and kidney from newborn and 1-, 7-, 21-, 35-, 56-, and 210-day-old domestic pigs. Fresh tissue homogenates were assayed under nine concentrations of γ-BB from 0 to 1.5 mM. Substrate inhibition associated with age was observed at ≥0.6 mM of γ-BB. Hepatic activity was low at birth but increased after 1 day. By 21 days, the activity rose by 6.6-fold (P < 0.05) and remained constant after 56 days. Renal activity was higher than in liver at birth but remained constant through 35 days. By 56 days, the velocity increased by 44% over the activity at birth (P < 0.05). The apparent Km for γ-BB at birth on average was 2.8-fold higher than at 1 day. The Km value was 60% higher in kidney than liver during development but showed no difference in adult pigs. The total organ enzyme activity increased by 130-fold for liver and 18-fold for kidney as organ weight increased from birth to 56 days. In conclusion, age and substrate affect γ-BBH specific activity and Km for γ-BB in liver and kidney. Whereas the predominant organ for carnitine synthesis is likely the kidney at birth, the liver appears to predominate after the pig exceeds 7 days of age.
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