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Nutritional Methodology

Fractional Synthesis Rates of DNA and Protein in Rabbit Skin Are Not Correlated^1,2

Xiao-jun Zhang^*,, David L. Chinkes^*,, Zhanpin Wu^*,,3, Wenjun Z. Martini^*,,4 and Robert R. Wolfe^*,,**,5

^* Metabolism Unit, Shriners Hospital for Children and Departments of Surgery and ^** Anesthesiology, University of Texas Medical Branch, Galveston, TX 77550

⁵To whom correspondence should be addressed. E-mail: rwolfe{at}utmb.edu.

We developed a method for measurement of skin DNA synthesis, reflecting cell division, in conscious rabbits by infusing D-[U-¹³C₆]glucose and L-[¹⁵N]glycine. Cutaneous protein synthesis was simultaneously measured by infusion of L-[ring-²H₅]phenylalanine. Rabbits were fitted with jugular venous and carotid arterial catheters, and were studied during the infusion of an amino acid solution (10% Travasol). The fractional synthetic rate (FSR) of DNA from the de novo nucleotide synthesis pathway, a reflection of total cell division, was 3.26 ± 0.59%/d in whole skin and 3.08 ± 1.86%/d in dermis (P = 0.38). The de novo base synthesis pathway accounted for 76 and 60% of the total DNA FSR in whole skin and dermis, respectively; the contribution from the base salvage pathway was 24% in whole skin and 40% in dermis. The FSR of protein in whole skin was 5.35 ± 4.42%/d, which was greater (P < 0.05) than that in dermis (2.91 ± 2.52%/d). The FSRs of DNA and protein were not correlated (P = 0.33), indicating that cell division and protein synthesis are likely regulated by different mechanisms. This new approach enables investigations of metabolic disorders of skin diseases and regulation of skin wound healing by distinguishing the 2 principal components of skin metabolism, which are cell division and protein synthesis.

KEY WORDS: • stable isotopes • mass spectrometer • fractional synthetic rate • rabbits

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