TY - JOUR
T1 - Decarboxylases involved in polyamine biosynthesis and their inactivation by nitric oxide
AU - Hillary, Rebecca A.
AU - Pegg, Anthony E.
N1 - Funding Information:
This research was supported in part by grant CA-18138 from NCI. We are very grateful to Dr. L.J. Ignarro and Dr. P.M. Bauer for providing information and discussion of the possible interactions of NO with polyamine metabolism. Space limitations limit the number of references that are included and many valuable contributions to this field have therefore been omitted.
PY - 2003/4/11
Y1 - 2003/4/11
N2 - Polyamines are ubiquitous cellular components that are involved in normal and neoplastic growth. Polyamine biosynthesis is very highly regulated in mammalian cells by the activities of two key decarboxylases acting on ornithine and S-adenosylmethionine. Recent studies, which include crystallographic analysis of the recombinant human proteins, have provided a detailed knowledge of their structure and function. Ornithine decarboxylase is a PLP-requiring decarboxylase, whereas S-adenosylmethionine decarboxylase (AdoMetDC) contains a covalently bound pyruvate prosthetic group. Both enzymes have a key cysteine residue, which is involved in protonation of the Schiff base intermediate C α to form the product. These residues, Cys360 in ornithine decarboxylase (ODC) and Cys82 in AdoMetDC, react readily with nitric oxide (NO), which is therefore a potent inactivator of polyamine synthesis. The inactivation of these enzymes may mediate some of the antiproliferative actions of NO.
AB - Polyamines are ubiquitous cellular components that are involved in normal and neoplastic growth. Polyamine biosynthesis is very highly regulated in mammalian cells by the activities of two key decarboxylases acting on ornithine and S-adenosylmethionine. Recent studies, which include crystallographic analysis of the recombinant human proteins, have provided a detailed knowledge of their structure and function. Ornithine decarboxylase is a PLP-requiring decarboxylase, whereas S-adenosylmethionine decarboxylase (AdoMetDC) contains a covalently bound pyruvate prosthetic group. Both enzymes have a key cysteine residue, which is involved in protonation of the Schiff base intermediate C α to form the product. These residues, Cys360 in ornithine decarboxylase (ODC) and Cys82 in AdoMetDC, react readily with nitric oxide (NO), which is therefore a potent inactivator of polyamine synthesis. The inactivation of these enzymes may mediate some of the antiproliferative actions of NO.
UR - https://www.scopus.com/pages/publications/1242318563
UR - https://www.scopus.com/pages/publications/1242318563#tab=citedBy
U2 - 10.1016/S1570-9639(03)00088-8
DO - 10.1016/S1570-9639(03)00088-8
M3 - Article
C2 - 12686127
AN - SCOPUS:1242318563
SN - 1570-9639
VL - 1647
SP - 161
EP - 166
JO - Biochimica et Biophysica Acta - Proteins and Proteomics
JF - Biochimica et Biophysica Acta - Proteins and Proteomics
IS - 1-2
ER -