Introduction: There are two types of enzymes present at all time in the blood, they are: 1. Functional plasma enzymes: they perform physiological function in the blood like lipoprotein lipase, most of these enzymes are synthesized and secreted by liver. 2. Non-functional plasma enzymes: they perform no physiological function in the plasma and mostly arise from destruction of RBCs, Tissue damage caused by injury or disease can cause marked increase in their level, so measurement of these enzymes level can help in diagnosis and prognosis of diseases, the most important non- functional plasma enzymes are:
1. Transaminases: Two enzymes of this group are considered as non-functional plasma enzymes, Alanine transaminase (ALT or SGPT) and Aspartate transaminase (AST or SGOT). Organ: Mainly the liver, but also found in other tissue. Function: both enzymes catalyze the transfer of amino group from an amino acid to another. ALT is having a role in alanine cycle catalyzing the reaction:
AST is catalyzing the reaction: Aspartate + -ketoglutarate oxaloacetate + glutamate Normal value: Male Female ALT 45 IU/L 34 IU/L AST 8 40 IU/L 6 34 IU/L * IU for International unit AST/ALT ratio: In healthy people ALT > AST Diagnosis: In liver disease, this enzymes "leak out" of hepatocytes reaching the circulation, leading to marked increase in their concentration in blood. So, increase in these enzymes value in blood indicates liver disease as hepatitis and liver cirrhosis. Change in AST/ALT ratio varies as follow: - AST/ALT is normally < 1.0 and is also < 1.0 in viral hepatitis (albeit with extremely high levels of both AST and ALT). - When AST/ALT > 1.0 but < 2.0, it is likely to be associated with cirrhosis Al khoms Medical College Ibrahim Sobhi Zorob
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- When AST/ALT > 2.0, it is more likely to be associated with alcoholic hepatitis or hepatocellular carcinoma. 2. Alkaline Phosphatase: Organ: throughout the entire body but mainly in liver, kidney, bone and placenta. Function: is a hydrolase enzyme responsible for removing phosphate group from many types of molecules. One of its isoenzymes, ALPL (tissue- nonspecific isozyme) is found in bone (and other tissue) and is thought to have a function in matrix mineralization. Normal value: in normal adult, normal alkaline phosphatase level in plasma ranges between 20 to 140 IU/L. Diagnosis: elevated plasma level of alkaline phosphatase indicate variety of diseases, mainly associated with bone such as Osteomalacia, rickets, vitamin D deficiency , Fractured bone, Pagets disease , osteosarcoma, and bone metastases of cancer specially prostatic cancer . Elevated level of this enzyme may also indicate liver diseases (Cholestasis, cirrhosis tumors (Breast carcinoma, Colon cancer, Lung cancer and Hodgkin lymphoma) Also, some diseases may cause plasma levels of alkaline phosphatase to drop below normal value, such as Hypophosphatasia (an autosomal recessive disease). 3. Acid Phosphatase: Organ: many organs, but the most important in diagnosis is prostatic acid phosphatase present in prostate. Function: like alkaline phosphatase, it removes phosphate group, but this enzyme works in acidic pH. In prostate, its associated with the liquefaction process of semen. Normal value: in normal adult, its normal level is 0.2 - 1.8 IU/L (some sources say its between 0 and 0.8 U/L). Diagnosis: high levels of prostatic acid phosphatase indicate prostate cancer. Highest level of this enzyme occurs in metastasized prostate cancer. Also, some other diseases (as Pagets disease, hyperparathyroidism, sickle-cell disease, multiple myeloma and lysosomal storage diseases as Gauchers disease) are associated with moderate increase in acid phosphatase plasma level.
4. Lactate Dehydrogenase: Organ: Lactate dehydrogenase (LDH) is having 5 isoenzymes: LDH-1 (4H) is found in heart and RBCs and is the most important in diagnosis. LDH-2 (3H1M) - in the reticuloendothelial system LDH-3 (2H2M) - in the lungs Al khoms Medical College Ibrahim Sobhi Zorob
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LDH-4 (1H3M) - in the kidneys, placenta, and pancreas LDH-5 (4M) - in the liver and striated muscle Function: the enzyme catalyzes the conversion of pyruvate to lactate, using NADH+H as a cofactor (converting it to NAD), this reaction is important to provide continuous supply of NAD during anaerobic glycolysis. Normal value: in normal adult, its level in plasma ranges between 105 - 333 IU/L. Diagnosis: higher level of LDH-1 in plasma indicates myocardial infraction. Also, cancer cells increase the level of lactate dehydrogenase because cancer cells use anaerobic glycolysis even in the presence of oxygen. Hemolysis of erythrocytes (RBCs) is also associated with the increase in LDH level because RBCs depend on anaerobic glycolysis only and have large amount of LDH.
5. Amylase: Organ: in saliva secreted by salivary glands and in pancreatic juice secreted by pancreas. Function: the enzyme catalysis the hydrolysis of starch to starch dextrins in the mouth first, then to maltose and isomaltose by pancreatic amylase in the small intestine. Normal value: Normally, its plasma level ranges between 23 to 85 U/L (some say its between 40 to 140 U/L) Diagnosis: increased concentration of amylase in plasma is often associated with acute pancreatitis.
6. Lipase: Organ: mainly by pancreas. Function: the enzyme is responsible for digestion of triacylglycerol in small intestine. Normal value: in normal adult results are between 0 to 160 units per liter. This test requires the subject to be fasting (do not eat or drink for 8 hours) Diagnosis: the elevated amount of the enzyme in the plasma indicate variety of diseases including pancreatitis and cancer of the pancreas, also duodenal ulcer and Celiac disease is associated with increase concentration of this enzyme.
7. Creatine kinase: Organ: in many tissues that consumes ATP rapidly (brain, retina especially in muscles. Al khoms Medical College Ibrahim Sobhi Zorob
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Function: the enzyme is used as an energy reservoir for the rapid buffering and regeneration of ATP in situ, as well as for intracellular energy transport. Normal value: normally between 10 - 120 micrograms per liter (mcg/L). Diagnosis: because the enzyme is present mainly in muscles, increased amount of CK enzyme in plasma is associated with muscle diseases, this includes rhabdomyolysis (severe muscle breakdown), muscular dystrophy and myocardial infraction.
8. Gamma-glutamyl transpeptidase: Organ: in many tissues, but mainly the liver. Function: the enzyme is present in the cell membrane and is involved in the transfer of amino acids across the cellular membrane, its also used in leukotriene metabolism and glutathione metabolism. Normal value: between 15-85 IU/L in males and 5-55 IU/L in females. Diagnosis: increased concentrations of this enzyme in the plasma is associated with liver diseases including hepatitis, its also increased in alcohol abuse, diabetes and block of bile flow from the liver.