Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale Medicine Thesis Digital Library School of Medicine 1965 Some properties of mouse mastocytoma histidine decarboxylase Walter W. Noll Yale University Follow this and additional works at: http://elischolar.library.yale.edu/ymtdl Recommended Citation Noll, Walter W., "Some properties of mouse mastocytoma histidine decarboxylase" (1965). Yale Medicine Thesis Digital Library. 2991. http://elischolar.library.yale.edu/ymtdl/2991 This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale Medicine Thesis Digital Library by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact [email protected]. 3 9002 06584 7247 SOME PROPERTIES OF MOUSE MASTOCYTOMA HISTIDINE DECARBOXYLASE WALTER W. NOLL X 9 6 5 MUDD LIBRARY Medical YALE MEDICAL LIBRARY Digitized by the Internet Archive in 2017 with funding from The National Endowment for the Humanities and the Arcadia Fund https://archive.org/details/somepropertiesofOOnoll SOME PROPERTIES OF MOUSE MASTOCYTOMA HISTIDINE DECARBOXYLASE by Walter W. Noll, B. A. A thesis submitted In partial fulfillment of the requirements for the degree of Doctor of Medicine Department of Pharmacology Yale University School of Medicine April, 1965 £(,90 Acknowledgements The study reported here was carried out at the Psychopharmacology Research Laboratories, Veterans Administration Hospital, Sepulveda, California. The author wishes to thank William G. Clark, Ph.D., for providing the laboratory facilities and funds which made this study possible, and Jack R. Cooper, Ph.D., Yale University School of Medicine, for his sponsor¬ ship. Special thanks are due Dorothea Aures, Ph.D., for her patient and friendly guidance. Table of Contents I. Introduction PP. 1-7 II. Materials 8 III. Methods ,, 9-14 IV'. Results 15-19 V. Discussion 20-23 V. Summary 24 VI. Tables and Figures Table 1. 3,4 Table 2. 16 Table 3. 16 Table 4. 23 Figure 1. 14 Figure 2. 17 Figure 3. 18 VII. References 25-30 -1- Introduction A mammalian histidine decarboxylase was first de¬ scribed in 1936 by Werle (64). Since then, enzymes that catalyze the decarboxylation of histidine have been demon¬ strated in many mammalian species and tissues. It has become clear that all of these enzymes are not identical, that they have different properties in different tissues, and that species differences do exist. A broad classifi¬ cation can be made, however, on the basis of substrate specificity, the pH at which the enzyme exhibits maximal activity, and the effects of various enzyme inhibitors and activators. Two main types emerges (i) an aromatic L-amino acid decarboxylase (29) which decarboxylates a wide variety of natural and synthetic aromatic amino acids including histidine (29, 62); this enzyme exhibits maximum activity in an alkaline medium (pH >8), is strongly in¬ hibited by alpha-methyl DOPA (a strong inhibitor of 3,4-dihydroxyphenylalanlne (DOPA) decarboxylase), and is activated in vitro by the addition of a small amount of benzene (6l). It is probably identical to the DOPA decarboxylase and 5-hydroxytryptophan (5-HTP) decarboxyl¬ ase of rabbit and guinea pig kidney (29, 45, 62). (li) a specific L-histidine decarboxylase which seems to decar- boxylate only histidine, is most active at slightly acid 2- or neutral pH, is inhibited only slightly or not at all by alpha-methyl DOPA, and is either unaffected or inhibited in vitro by the addition of a small amount of benzene. These properties of histidine decarboxylase from many mammalian sources are summarized in Table 1. In addition, the affinity for the substrate, L-histidine, differs greatly between these two types, specific histidine decarboxylase having a much lower Michaelis-Menten constant (Km) than aromatic L-amino acid decarboxylase (33, 63). Both types of enzymes share a requirement for the coenzyme pyridoxal-5-phosphate, and consequently both are Inhibited by compounds such as hydroxylamine and semi- carbazlde which react with pyridoxal phosphate (3, 8, 9, 10, 31, 38, 41, 46, 48, 54). The specific enzyme appears to bind this cofactor more loosely than aromatic amino acid decarboxylase, the former enzyme losing activity much more rapidly with dialysis (46, 48). Although a metal ion requirement has been demonstrated for bacterial histidine decarboxylase (6), this has not been shown for the mam¬ malian enzyme. The addition of EDTA (lO-^ M) has no effect on the mammalian enzyme activity (63). In addition to the classification discussed above, which considers only the jUn vitro biochemical behavior of the enzymes, groupings have been made which include functional considerations as well. 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