A friend asked me why there are two transaminases in liver function tests every time during a physical examination? These two items only differ by the characters”丙” and ”草”, and both tests are essential, belonging to the routine liver function tests. Although the values measured each time are quite similar, but missing any one is not acceptable. As for why there are two transaminases, let’s briefly understand these two transaminases brothers.
1. Basic Information
Glutamic-pyruvic transaminase, full name glutamate-pyruvate transaminase(glutamic-pyruvic transaminase, GPT), also known as alanine aminotransferase (ALT), is an enzyme that catalyzes the transfer of an amino group from α-ketoglutarate to alanine, producing glutamate and pyruvate (the reaction is reversible).
Glutamic-oxaloacetic transaminase, full name glutamate-oxaloacetate transaminase(glutamic oxaloacetic transaminase, GOT), also known as aspartate aminotransferase (AST), is an enzyme that catalyzes the transfer of an amino group from aspartate to α-ketoglutarate, producing oxaloacetate and glutamate (the reaction is reversible).
2. Clinical Significance of Elevation
Glutamic-pyruvic transaminase is most abundant in the liver, primarily located in the cytoplasm of liver cells, with a concentration 1000-3000 times higher than in serum. It can also be found in the kidneys, heart, skeletal muscles, and other organs. Elevation of glutamic-pyruvic transaminase is commonly seen in chronic heavy drinkers, patients with viral hepatitis, cirrhosis or liver cancer, toxic hepatitis, biliary diseases, and other conditions that can cause liver damage. Additionally, glutamic-pyruvic transaminase can also be elevated in cases of myocardial injury due to heart disease.
Glutamic-oxaloacetic transaminase is most abundant in the myocardium, followed by the liver and skeletal muscles. Therefore, after its discovery in the 1950s, glutamic-oxaloacetic transaminase was primarily used for diagnosing acute myocardial infarction. However, since AST lacks tissue specificity, a simple elevation of serum AST cannot diagnose myocardial injury; its sensitivity for diagnosing myocardial infarction is 77.7%, with a specificity of only 53.3%. Due to its poor specificity, with the emergence of high-specificity tests such as creatine kinase isoenzymes and cardiac troponins, AST has gradually been phased out of myocardial infarction diagnosis. On the other hand, in liver diseases, glutamic-oxaloacetic transaminase can also be elevated, and basically, any liver and biliary diseases causing elevation of glutamic-pyruvic transaminase will also lead to an increase in glutamic-oxaloacetic transaminase.
3. Application of AST/ALT Ratio in Liver Disease Diagnosis
Since liver diseases that can cause elevation of ALT generally also cause elevation of AST, we return to the question posed by my friend: why are both transaminases tested simultaneously? To answer this question, we first need to look at the composition of glutamic-oxaloacetic transaminase. Glutamic-oxaloacetic transaminase has two isoenzymes, existing in the mitochondria (mAST) and the cytoplasm (sAST) of liver cells, with the majority located in the mitochondria (about 70%-80%). In mild liver cell damage, although the liver cells are damaged, the mitochondria remain intact, and only sAST is released into the blood; however, when the damage is severe, mAST will also be released into the blood, thus increasing serum AST activity corresponding to the degree of liver cell damage.
In acute hepatitis, the degree of liver cell damage is mild, occurring only at the liver cell membrane, so only the cytoplasmic enzyme is released, whileALT is primarily located in the cytoplasm of liver cells, resulting in a higher elevation of ALT than AST, leading to an AST/ALT ratio of less than 1. As the disease progresses, with continued damage and worsening condition, the mitochondrial integrity of liver cells is compromised, and since AST has a higher content in the mitochondria, the elevation of AST surpasses that of ALT, thus changing the AST/ALT ratio from less than 1 to greater than 1. The AST/ALT ratios for acute hepatitis, chronic hepatitis, cirrhosis, and liver cancer vary based on the condition and duration of the disease, specifically: 0.61±0.27, 0.91±0.42, 1.85±0.99, and 2.37±1.02, respectively.
4.Current Research
Typically, the ratio of the two transaminases is mainly used for diagnosing and treating liver diseases, but in recent years, researchers have found that the ratio of the two transaminases can also play a role in diagnosing and treating other diseases. For example, in a study of 231 gastric adenocarcinoma patients undergoing chemotherapy, the ALT/AST ratio was found to be an independent prognostic factor, with patients having ALT/AST ≤ 0.8 at a greater risk of mortality than those with ALT/AST > 0.8. In a study of Korean men, the AST/ALT ratio was found to be associated with the risk of esophageal cancer, with individuals having an AST/ALT ≥ 2 at a higher risk of developing esophageal cancer.
Therefore, glutamic-pyruvic transaminase and glutamic-oxaloacetic transaminase are not two redundant tests; they complement each other and serve as effective indicators for assessing liver disease progression and prognosis, holding significant importance in differential diagnosis and prognostic evaluation of liver diseases.
