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Induction of Tyrosine Transaminase Activity by Hydrocortisone in Vitamin B-6-deficient Rats^1,2,

Department of Biochemistry, West Virginia University School of Medicine, Morgantown, West Virginia 26506

The effect(s) of vitamin B-6 deficiency on the hormonal induction of tyrosine transaminase and the synthesis of proteins in rat liver were studied. Hydrocortisone hemisuccinate was administered intraperitoneally, and at different time intervals, the activity of tyrosine transaminase and incorporation of ³H-labeled L-amino acids into liver proteins were determined. Incorporation of labeled precursor into tyrosine transaminase was also determined immunochemically in terms of antibody (antitransaminase)-specific precipitable radioactivity. Vitamin B-6 deficiency directly affected both enzyme induction and protein synthesis. The specific activity of hepatic tyrosine transaminase was three times greater in ad libitum or pair-fed stock diet controls than that in deficient animals. Induction of the enzyme by hydrocortisone in vitamin B-6 deficiency was characterized by: (a) an early peak induction time (3.5–6 hours) when in vivo protein synthesis was normal; (b) a delayed incorporation of label into protein, including tyrosine transaminase (8–10 hours); (c) an increased rate of protein synthesis; and (d) a failure of cycloheximide to block the rise in enzymatic activity in spite of its effective inhibition of label incorporation into liver proteins. On the other hand, hormonal induction of the enzyme in stock diet-fed control animals was characterized by: (a) the occurrence of peak enzyme induction, in vivo protein synthesis, and antitransaminase-precipitable radioactivity after 6 hours treatment with the hormone; and by (b) effective inhibition by cycloheximide of both the rise in enzyme activity and the in vivo incorporated radioactivity into liver proteins, including transaminase. The data are interpreted in terms of the essentiality of dietary vitamin B-6 availability for both liver protein synthesis and hormonal induction of tyrosine transaminase.

KEY WORDS: • vitamin B-6 deficiency • transaminase induction • hydrocortisone

¹ This study was supported by USPHS grant CA 13759 from the National Cancer Institute, by general research support grants 5 S01RR05347-13 from the School of Dentistry, and by award IN-76K from the local branch of the American Cancer Society to one of us (GPT). Results were submitted to the Graduate School, West Virginia University in partial fulfillment of the requirements for the Degree of Master of Science (TP).

² Preliminary results were presented at the 162nd American Chemical Society National Meeting, Washington, D.C., September 13–17, 1971, Abstract no. 111.

³ Present address: Worthington Biochemicals Corporation, Freehold, N. J.

⁴ To whom requests for reprints should be addressed.

Manuscript received 12 September 1973.