Function and Control of Liver Alkaline Phosphatase

Abstract

Abstract Partial hepatectomy causes a large rise in the activity of liver alkaline phosphatase that takes place exclusively in the plasma membrane. The activity of the membrane phosphatase can be raised in the livers of unoperated rats by infusing the animals with glycine, heparin, phosphorylcholine, phosphatidylcholine, or cortisol. The effects of glycine and heparin are additive. l-Serine is as effective as glycine but none of the other amino acids tested has activity. Any of several compounds that are known to increase the supply of fatty acids to the liver can substitute for heparin. The increase in phosphatase activity is accompanied by rises in the rates of excretion of choline and phosphatidylcholine into the bile. Folate blocks the increases in the phosphatase activity and in the excretion of choline that are ordinarily produced by a mixture of glycine and heparin or by cortisol. Neither phosphorylcholine nor alkaline phosphatase activity is detectable in samples of freshly collected rat bile. The membrane phosphatase is able to hydrolyze phosphorylcholine. Taken together, these observations have suggested that at least one of the functions of the alkaline phosphatase of the liver membrane is to hydrolyze phosphorylcholine so that choline can be transported across the bile canalicular membrane. The level of the enzyme activity appears to be controlled by the quantity of phosphorylcholine that is available for excretion into the bile. Partial hepatectomy leads to alterations in 1-carbon and phospholipid metabolism that result in increases in liver phosphorylcholine and in the activity of the membrane phosphatase. The rise in alkaline phosphatase activity is not essential for the entry of the liver cell into the period of DNA replication.