Ontogeny of carnitine biosynthesis in Sus scrofa domesticus, inferred from γ-butyrobetaine hydroxylase (dioxygenase) activity and substrate inhibition

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2020-07, Vol.319 (1), p.R43-R49
• Main Authors: Xi, Lin, Peffer, Pasha Lyvers, Woodworth, Jason Clark, Odle, Jack
• Format: Article
• Language: English
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00051.2020

Gamma-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 on the enzyme's specific activity, kinetics of γ-BBH were measured in liver and kidney from domestic pigs in newborn, 1, 7, 21, 35, 56 and 210 day-old. Fresh tissue homogenates were assayed under 9 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 24 h. By 3 wk, the activity rose by 6.6-fold (p < 0.05) and remained constant after 8 wk. Renal activity was higher than in liver at birth, but remained constant through 5 wk. By 8 wk, the velocity increased by 44% over the activity at birth (p < 0.05). The apparent K for γ-BB at birth on average was 2.8 fold higher than at 24 h. The K 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 8 wk. In conclusion, age and substrate affect γ-BBH specific activity and K for γ-BB in liver and kidney. While the predominant organ for carnitine synthesis is likely the kidney at birth, the liver appears to predominate after the pig exceeds 7 day of age.