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Human Pyrimidine Metabolism FREE

Sherman M. Weissman, MD
[+] Author Affiliations

Reprint requests to National Cancer Institute, Metabolism Service, Bethesda, Md 20014.


From the Metabolism Service, National Cancer Institute, National Institutes of Health, Bethesda, Md 20014.


JAMA. 1966;195(1):27-30. doi:10.1001/jama.1966.03100010083020
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Studies of pyrimidine metabolism in man have assumed interest in recent years with the recognition of specific alterations in their synthesis and excretion in certain diseases. Further, several pyrimidine antimetabolites have been introduced into cancer chemotherapy, and the metabolic alterations produced by some of these, 6-azauridine, has been a subject of physiological and biochemical interest.

The pyrimidine ring is a common component of biologically active substances. It occurs in a variety of therapeutic compounds such as xanthine oxidase inhibitors, antimetabolites, antithyroid substances, sedatives, and vitamins. Among natural substances, pyrimidines occur most abundantly in the nucleic acids. Ribonucleic acids contain large amounts of uracil and cytosine derivatives (Fig 1), and deoxyribonucleic acid (DNA) contains cytosine and thymine derivatives (Fig 1). Pyrimidines also appear in a variety of acid-soluble phosphorylated cofactors, such as uridine diphosphoglucose, which play a central role in carbohydrate and lipid metabolism.

Normal Pyrimidine Metabolism  The pathway of pyrimidine

REFERENCES

Schulman, M.P.: " Purines and Pyrimidines ," in Greenberg, D.M.: Metabolic Pathways , New York: Academic Press, Inc., 1961;, vol 2, pp 389-467.
Smith, L.H., Jr., and Baker, F.A.:  Pyrimidine Metabolism in Man: I. The Biosynthesis of Orotic Acid , J Clin Invest 38:798-809 ( (May) ) 1959;.
Adler, M., and Gutman, A.B.:  A Uridine Isomer (5-Ribosyluracil) in Human Urine , Science 130:862-863 ( (Oct 2) ) 1959;.
Adams, M.J.; Davis, T.; and Nakatani, N.:  Purine and Pyrimidine Metabolism in Normal and Leukemic Subjects , Amer J Med 28:726-734 ( (May) ) 1960;.
Cohn, W.E.:  Pseudouridine, a Carbon-Carbon Linked Ribonucleoside in Ribonucleic Acid: Isolation, Structure and Chemical Characteristics , J Biol Chem 235:1488-1498 ( (May) ) 1960;.
Weissman, S.M., et al:  Pseudouridine Metabolism: III. Studies With Isotopically Labelled Pseudouridine , J Lab Clin Med 60:40-47 ( (July) ) 1962;
Weiss, S.B, and Legault-Demare, J.:  Pseudouridine Formation: Evidence for RNA as an Intermediate , Science 149:429-431 ( (July 23) ) 1965;.
Weissman, S.M., et al:  The Metabolism of Ring-Labelled Orotic Acid in Man , J Clin Invest 41:1546-1552 ( (July) ) 1962;.
Weissman, S.M.; Lewis, M.; and Karon. M.:  The Metabolism of Isotopically Labelled Uracil and Uridine in Man , Metabolism 12:60-67 ( (Jan) ) 1963;.
Weissman, S.M.; Eisen, A.Z.; and Karon, M.:  Pseudouridine Metabolism: II. Excretion in Various Disease States , J Lab Clin Med 59:852-858 ( (May) ) 1962;.
Weissman, S.M.; Lewis, M.; and Karon, M.:  Pseudouridine Metabolism: IV. Excretion of Pseudouridine and Other Nitrogenous Metabolites in Chronic Leukemia , Blood 22:657-663 ( (Dec) ) 1963;.
Lewis, M.; Weissman, S.M.; and Karon, M.:  Studies on the Pseudouridinia of Chronic Lymphatic Leukemia , Blood 24:567-576 ( (Nov) ) 1964;.
Huguley, C.M., Jr., et al:  Refractory Megaloblastic Anemia Associated With Excretion of Orotic Acid , Blood 14:615-634 ( (June) ) 1959;.
Becroft, D.M.O., and Phillips, L.I.:  Hereditary Orotic Aciduria and Megaloblastic Anemia: A Second Case With Response to Uridine , Brit Med J 1:547-552 ( (Feb 27) ) 1965;.
Smith, L.H., Jr.; Huguley, C.M., Jr.; and Bain, J.A. in Stanbury, J.B.; Wyngaarden, J.B.; and Frederickson, D.S. (eds.): The Metabolic Basis of Inherited Disease , New York: McGraw-Hill Book Co., Inc.. 1964;.
Smith, L.H.. Jr.; Sullivan, M.; and Huguley, C.M.:  Pyrimidine Metabolism in Man: IV. The Enzymatic Defect of Orotic Aciduria , J Clin Invest 40:656-664 ( (April) ) 1961;.
Smith, L.H., Jr.:  Hereditary Orotic Aciduria-Pyrimidine Auxotrophism in Man , Amer J Med 38:1-6 ( (Jan) ) 1965;.
Handschumacher, R.E., et al:  Summary of Current Information on 6-Azauridine , Cancer Chemother Rep 21:1-18 ( (Aug) ) 1962;.
Fallon, H.J. et al:  The Uricosuria and Orotic Aciduria Induced by 6-Azauridine , J Clin Invest 40:1906-1914 ( (Oct) ) 1961;.
Buttoo, A.S; Israels, M.C.G.; and Wilkinson, J.F.:  Hypocholesterolemia and Orotic Aciduria During Treatment With 6-Azauridine , Brit Med J 1:552-554 ( (Feb 27) ) 1965;.
Handschumacher, R.E., and Welch, A.D.: " Antimetabolites and Nucleic Acid Metabolism: V. Structural Analogs of Pyrimidines and Their Effects on Nucleic Acid Metabolism ," in Chorgoff, E.. and Davidson, J.N.: The Nucleic Acids , New York: Academic Press, Inc., 1960;, pp 498-506.
Zubrod, C.G.: " The Limited Usefulness of 5-Fluorourial (5-FU) and 5-Fluorodeoxyuridine (5-FUDR) in the Management of Patients With Adenocarcinomas ," in Ingelfinger, F. (ed.): Controversy in Internal Medicine , Philadelphia: W.B. Saunders, Co., to be published.

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Schulman, M.P.: " Purines and Pyrimidines ," in Greenberg, D.M.: Metabolic Pathways , New York: Academic Press, Inc., 1961;, vol 2, pp 389-467.
Smith, L.H., Jr., and Baker, F.A.:  Pyrimidine Metabolism in Man: I. The Biosynthesis of Orotic Acid , J Clin Invest 38:798-809 ( (May) ) 1959;.
Adler, M., and Gutman, A.B.:  A Uridine Isomer (5-Ribosyluracil) in Human Urine , Science 130:862-863 ( (Oct 2) ) 1959;.
Adams, M.J.; Davis, T.; and Nakatani, N.:  Purine and Pyrimidine Metabolism in Normal and Leukemic Subjects , Amer J Med 28:726-734 ( (May) ) 1960;.
Cohn, W.E.:  Pseudouridine, a Carbon-Carbon Linked Ribonucleoside in Ribonucleic Acid: Isolation, Structure and Chemical Characteristics , J Biol Chem 235:1488-1498 ( (May) ) 1960;.
Weissman, S.M., et al:  Pseudouridine Metabolism: III. Studies With Isotopically Labelled Pseudouridine , J Lab Clin Med 60:40-47 ( (July) ) 1962;
Weiss, S.B, and Legault-Demare, J.:  Pseudouridine Formation: Evidence for RNA as an Intermediate , Science 149:429-431 ( (July 23) ) 1965;.
Weissman, S.M., et al:  The Metabolism of Ring-Labelled Orotic Acid in Man , J Clin Invest 41:1546-1552 ( (July) ) 1962;.
Weissman, S.M.; Lewis, M.; and Karon. M.:  The Metabolism of Isotopically Labelled Uracil and Uridine in Man , Metabolism 12:60-67 ( (Jan) ) 1963;.
Weissman, S.M.; Eisen, A.Z.; and Karon, M.:  Pseudouridine Metabolism: II. Excretion in Various Disease States , J Lab Clin Med 59:852-858 ( (May) ) 1962;.
Weissman, S.M.; Lewis, M.; and Karon, M.:  Pseudouridine Metabolism: IV. Excretion of Pseudouridine and Other Nitrogenous Metabolites in Chronic Leukemia , Blood 22:657-663 ( (Dec) ) 1963;.
Lewis, M.; Weissman, S.M.; and Karon, M.:  Studies on the Pseudouridinia of Chronic Lymphatic Leukemia , Blood 24:567-576 ( (Nov) ) 1964;.
Huguley, C.M., Jr., et al:  Refractory Megaloblastic Anemia Associated With Excretion of Orotic Acid , Blood 14:615-634 ( (June) ) 1959;.
Becroft, D.M.O., and Phillips, L.I.:  Hereditary Orotic Aciduria and Megaloblastic Anemia: A Second Case With Response to Uridine , Brit Med J 1:547-552 ( (Feb 27) ) 1965;.
Smith, L.H., Jr.; Huguley, C.M., Jr.; and Bain, J.A. in Stanbury, J.B.; Wyngaarden, J.B.; and Frederickson, D.S. (eds.): The Metabolic Basis of Inherited Disease , New York: McGraw-Hill Book Co., Inc.. 1964;.
Smith, L.H.. Jr.; Sullivan, M.; and Huguley, C.M.:  Pyrimidine Metabolism in Man: IV. The Enzymatic Defect of Orotic Aciduria , J Clin Invest 40:656-664 ( (April) ) 1961;.
Smith, L.H., Jr.:  Hereditary Orotic Aciduria-Pyrimidine Auxotrophism in Man , Amer J Med 38:1-6 ( (Jan) ) 1965;.
Handschumacher, R.E., et al:  Summary of Current Information on 6-Azauridine , Cancer Chemother Rep 21:1-18 ( (Aug) ) 1962;.
Fallon, H.J. et al:  The Uricosuria and Orotic Aciduria Induced by 6-Azauridine , J Clin Invest 40:1906-1914 ( (Oct) ) 1961;.
Buttoo, A.S; Israels, M.C.G.; and Wilkinson, J.F.:  Hypocholesterolemia and Orotic Aciduria During Treatment With 6-Azauridine , Brit Med J 1:552-554 ( (Feb 27) ) 1965;.
Handschumacher, R.E., and Welch, A.D.: " Antimetabolites and Nucleic Acid Metabolism: V. Structural Analogs of Pyrimidines and Their Effects on Nucleic Acid Metabolism ," in Chorgoff, E.. and Davidson, J.N.: The Nucleic Acids , New York: Academic Press, Inc., 1960;, pp 498-506.
Zubrod, C.G.: " The Limited Usefulness of 5-Fluorourial (5-FU) and 5-Fluorodeoxyuridine (5-FUDR) in the Management of Patients With Adenocarcinomas ," in Ingelfinger, F. (ed.): Controversy in Internal Medicine , Philadelphia: W.B. Saunders, Co., to be published.
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