Molecular nature of three liver alkaline phosphatases detected by drug administration in vivo: differences between soluble and membranous enzymes.
1. Activities of alkaline phosphatase, liver-membranous, liver-soluble and serum-soluble, were dramatically induced in dogs by treatment with both phenobarbital and brovanexine. The treatment induced a 17-fold increase in membranous, a 155-fold increase in soluble, and a 105-fold increase in serum alkaline phosphatases. 2. There was no difference in the enzymatic behavior of the three forms of alkaline phosphatase, on heat stability, amino acid inhibition and optimum pH. 3. When the three alkaline phosphatases were treated initially with n-butanol, their apparent molecular size was identical. After treatment with phosphatidylinositol-specific phospholipase C, the liver-soluble and serum-soluble alkaline phosphatase were of the same molecular size. Liver-membranous alkaline phosphatase, however, was larger in molecular size than the other two forms, suggesting a difference between soluble and membranous alkaline phosphatase forms. 4. In terms of the sugar moiety of the three alkaline phosphatase forms, the membranous enzyme showed more of the higher affinity fraction and less of the lower affinity fraction of concanavalin A, compared with the soluble enzymes. 5. Consequently, it is possible that the membranous enzyme may be solubilized by an enzyme such as phosphatidylinositol-specific phospholipase C and modify further the sugar moiety of alkaline phosphatase molecules, resulting in serum alkaline phosphatase transfer from the soluble enzyme in liver.
Unakami
S
S
Department of Hematochemistry, Central Institute for Experimental Animals, Kawasaki, Japan.
Komoda
T
T
Watanabe
M
M
Tanimoto
Y
Y
Sakagishi
Y
Y
Ikezawa
H
H
D000469:Alkaline Phosphatase / Q000096:biosynthesis* / Q000097:blood; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002846:Chromatography, Affinity; D004285:Dogs; D004790:Enzyme Induction; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis* / Q000097:blood; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008970:Molecular Weight; D010634:Phenobarbital / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000201:enzymology
D001549:Benzamides; D007527:Isoenzymes; D000469:Alkaline Phosphatase; D005952:Glucose-6-Phosphatase; C012222:brovanexine; D010634:Phenobarbital