These are group of enzymes that hydrolyse phosphate esters at alkaline pH, although the physiological substrate is not known. Although present in several tissues, plasma component mainly contributed from liver, bone, intestine and placenta (during pregnancy). There are 2 liver derived isoenzymes. One derives from hepatocytes and other from exterior surface of biliary canalicular membrane. The function of hepatic ALP is thought to transport bile acids into bile.
Plasma ALP increases during cholestasis of biliary tract and this increase is due to de novo synthesis by increased translation of ALP mRNA rather than transcription. In cholestatic disease, due to biliary tract obstruction (intrahepatic bile ducts obstruction e.g primary biliary cirrhosis or common bile duct obstruction e.g. gallstones).
ALP rises before clinical jaundice appears. Pain over the liver, elevated ALP with normal bilirubin is strongly suggestive of hepatic space-occupying lesion, like intrahepatic tumor, or infiltrative disorder.
ALP also increases during bone growth or bone disease in which there is increased osteoblastic activity. But in hepatic osteodystrophy increase in ALP is not due to bone disease. So, measurement of ALP isoenzymes can be helpful to distinguish involvement of liver/bone/intestine or other tissue. Additional ALP band seen during pregnancy, malignancy is called Regan isoenzymes. Measurement GGT and its rising level indicate that increase in ALP is probably of hepatic origin.
Standard ALP assay:
ALP assay done after heating serum at 560C for 15 min which will destroy liver and bone isoenzymes but the placental isoenzymes remains unaffected.
These catalyze the transfer of an amino group from α-amino acid to α-oxo acid. Two most widely used enzymes are Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT).
AST found in liver, heart, skeletal muscle, kidney, brain, erythrocytes and lung. ALT is more specific to liver. However the increase in aminotransferase due to liver disease and those due to skeletal or cardiac muscle damage can be made by measuring creatine kinase or cardiac-specific troponins respectively.
These enzymes are increased during necrotic or damaged hepatocytes. During viral hepatitis there is marked increase in asymptomatic individuals, the specificity increasing with the increase in enzyme level. Increase 10 times URL is seen during acute (viral or drug-induced) or chronic (autoimmune) hepatitis. Elevated AST is also seen during obstructive jaundice, cardiac failure. Measurement of AST/ALP ratio is more diagnostic. Higher ratio is seen during hepatitis and lower ratio indicates cholestatic disorder. AST/ALT ratio of >2 indicates alcoholic hepatitis, especially mAST is elevated.
Mitochondrial isoenzymes of AST (mAST):
There are two forms of AST, cytosolic and mitochondrial. The mAST accounts for about 80% of total AST activity within liver cells. Increased ratio of mAST/total AST indicates chronic alcohol abuse irrespective of liver disease.
γ-Glutamyl transferase (γGT):
This is microsomal enzyme responsible for transfer of glutamyl group from γ-glutamyl peptides to other peptides or amino acids which is then transported across cell membrane. Although widely distributed except muscle, plasma activity is due to liver isoenzymes. Its measurement is useful in two circumstances. First, elevated γGT and ALP indicates increase in ALP is hepatic origin. Second, its increment indicates chronic alcohol consumption, remains elevated after abstinence.
This enzyme catalyses the hydrolysis of nucleoside 5’ phosphate e.g., AMP, releasing Pi. It is located in biliary canalicular and is increased on biliary cholestasis. The main advantage of this enzyme is it is not increased in any non hepatic condition where ALP would increase.