Biochemistry of Alkaline Phosphatase Isoenzymes

Abstract

The common forms of alkaline phosphatase, namely liver, bone, intestinal, placental, and kidney alkaline phosphatase are compared and contrasted. Their catalytic, inhibition, antigenic, and structural properties support the conclusion that these forms are coded for by at least three separate genetic loci. The liver/ bone/ “major” kidney types constitute one isoenzyme group while the intestinal/“minor” kidney and placental types constitute two further separate isoenzyme groups. Other properties, such as heat stability and charge, are probably determined by posttranslational modifications such as association with carbohydrate. There are various methods which are useful in separating isoenzymes, but none are satisfactory for accurate measurement of the activity of different types of alkaline phosphatase in mixtures. The location of alkaline phosphatase in the cell membranes of absorptive surfaces has led to theories concerning its function in transport. The nature of the substance which is transported is unknown for liver alkaline phosphatase, but synthesis of the isoenzyme is induced by cholestasis and increased concentrations of bile acids. It is thought that bone alkaline phosphate plays a role in bone calcification by hydrolyzing pyrophosphate which is an inhibitor of bone mineralization; its regulation is unclear. It has been variously suggested that the intestinal isoenzyme is involved in the transport of fatty acids, calcium, and phosphate. The controversy has yet to be resolved since some evidence exists for all three functions, although the role of the isoenzyme in calcium transport is likely to be, at best, secondary. Finally, other forms of alkaline phosphatase sometimes found in serum are briefly discussed. Some of these are found exclusively in cancer; they are the Regan and Nagao isoenzymes, which appear to correspond to different allelic forms of the placental isoenzyme, and the Kasahara isoenzyme which resembles an isoenzyme found in an FL amnion cell line. All three tumor forms probably represent derepression of normally repressed feto-placental genes. Particulate alkaline phosphatase is found in cholestasis and may represent either fragments of liver cell membrane or associations between the liver isoenzyme and various lipid moieties formed in the circulation. The immunoglobulin G-alkaline phosphatase complex is found rarely and seems to be a true immune complex.