Identification of a major hepatic copper binding protein as S-adenosylhomocysteine hydrolase.
The properties of a mouse liver copper binding protein (CuBP) and human placental S-adenosylhomocysteine hydrolase (SAHH) were compared to test the hypothesis that CuBP is SAHH. CuBP and SAHH migrated identically on SDS-polyacrylamide gel electrophoresis gels, and their 48-kDa monomers both self-associate to tetramers. Human placental SAHH cross-reacted with polyclonal antibodies to mouse liver CuBP, and CuBP from mouse liver cross-reacted with two monoclonal antibodies to human placental SAHH. A third monoclonal antibody to human placenta SAHH reacted weakly with the mouse liver protein but well with CuBP from human lymphoblasts. NAD(+)-activated CuBP has high SAHH enzymatic activity. Moreover, human placental SAHH, like mouse liver CuBP, has a single high affinity copper binding site per 48-kDa subunit. Thus, the data confirm that CuBP is SAHH, and SAHH is proposed to be a bifunctional protein with roles in sulfur-amino acid metabolism and copper metabolism. The copper binding activity of SAHH is proposed to play a significant role in the intracellular distribution of copper, and SAHH enzymatic activity may influence copper metabolism through its role in cysteine biosynthesis from methionine.
Bethin
K E
KE
Department of Biochemistry, State University of New York at Buffalo 14214, USA.
Petrovic
N
N
Ettinger
M J
MJ
D043383:Adenosylhomocysteinase; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism / Q000494:pharmacology; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011485:Protein Binding; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism
D002352:Carrier Proteins; D011994:Recombinant Proteins; C023548:copper-binding protein; D003300:Copper; D006867:Hydrolases; D043383:Adenosylhomocysteinase; C029892:cupric chloride