Biochemistry
Biochemistry
9th Edition
ISBN: 9781319114671
Author: Lubert Stryer, Jeremy M. Berg, John L. Tymoczko, Gregory J. Gatto Jr.
Publisher: W. H. Freeman
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Question
3. Hepatocellular carcinoma (HCC) is among the leading causes of cancer death worldwide. Studies of gene expression in HCC cells demonstrated that the enzyme ornithine aminotransferase (OAT) is upregulated in these cells. Ornithine (structure to the right) is both an intermediate in the urea cycle as well as a precursor for the synthesis of the nonessential amino acid proline. Unlike many aminotransferases, OAT acts on the side chain amine of ornithine rather than the alpha-amino group. wwwwwww (a) If OAT takes ornithine and alpha-ketoglutarate as substrates, draw the structures of the products released after catalysis. (b) What cofactor does OAT use and how is it linked to the enzyme? (c) Devise a strategy to alleviate HCC based on OAT and describe the specific steps required to accomplish this. What is a major challenge in this approach? What pre-clinical effects would you want to demonstrate before attempting to treat patients?
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Transcribed Image Text:3. Hepatocellular carcinoma (HCC) is among the leading causes of cancer death worldwide. Studies of gene expression in HCC cells demonstrated that the enzyme ornithine aminotransferase (OAT) is upregulated in these cells. Ornithine (structure to the right) is both an intermediate in the urea cycle as well as a precursor for the synthesis of the nonessential amino acid proline. Unlike many aminotransferases, OAT acts on the side chain amine of ornithine rather than the alpha-amino group. wwwwwww (a) If OAT takes ornithine and alpha-ketoglutarate as substrates, draw the structures of the products released after catalysis. (b) What cofactor does OAT use and how is it linked to the enzyme? (c) Devise a strategy to alleviate HCC based on OAT and describe the specific steps required to accomplish this. What is a major challenge in this approach? What pre-clinical effects would you want to demonstrate before attempting to treat patients?
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