Vitamin C Is Not Essential for Carnitine Biosynthesis in Vivo : Verification in Vitamin C-Depleted Senescence Marker Protein-30/Gluconolactonase Knockout Mice(Highlighted paper selected by Editor-in-chief,Biochemistry)

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Carnitine is an essential cofactor in the transport of long-chain fatty acids into the mitochondrial matrix and plays an important role in energy production via β-oxidation. Vitamin C (VC) has long been considered a requirement for the activities of two enzymes in the carnitine biosynthetic pathway, i.e., 6-N-trimethyllysine dioxygenase and γ-butyrobetaine dioxygenase. Our present study using senescence marker protein-30 (SMP30)/gluconolactonase (GNL) knockout (KO) mice, which cannot synthesize VC in vivo, led to the conclusion that this notion is not true. After weaning at 40d of age, SMP30/GNL KO mice were fed a diet lacking VC and carnitine,then given water containing 1.5g/l VC (VC(+)mice) or no VC (VC(-)mice) for 75d. Subsequently, total VC and carnitine levels were measured in the cerebrum, cerebellum, liver, kidney, soleus muscle, extensor digitorum longus muscle, heart, plasma and serum. The total VC levels in all tissues and plasma from VC(-) SMP30/GNL KO mice were negligible, i.e., <2% of the levels in SMP30/GNL KO VC (+) mice; however, the total carnitine levels of both groups were similar in all tissues and serum. In addition, carnitine was produced by incubated liver homogenates from the VC-depleted SMP30/GNL KO mice irrespective of the presence or absence of 1mM VC.Collectively, these results indicate that VC is not essential for carnitine biosynthesis in vivo.
公益社団法人日本薬学会の論文
2008-09-01