Alkaline Phosphatase

Alkaline phosphatases are GPI-anchored ectoenzymes that dephosphorylate a broad range of substrates at alkaline pH, functioning as dimeric metalloenzymes coordinated by zinc and magnesium ions. Humans express four isoenzymes: tissue-nonspecific alkaline phosphatase (ALPL) in liver, bone, and kidney, plus intestinal (ALPI), placental, and germ-cell forms. ALPL is essential for skeletal mineralization through hydrolysis of pyrophosphate and other phosphate esters, and its inherited deficiency causes hypophosphatasia, now treatable with enzyme replacement. Elevated serum alkaline phosphatase activity is a routine clinical marker of cholestatic liver disease and of increased bone turnover in Paget disease, metastatic bone lesions, and rickets.