They’re proteins that help speed up a chemical reaction in the liver. Blood tests, called liver function tests, are used to evaluate various functions in the liver. Examples of these functions are metabolism, filtration and excretion and storage, which are often performed by liver enzymes. But not all liver function tests measure enzyme function.
Liver enzymes are found in normal plasma and serum and can be divided into different groups.
- Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT). Together these enzymes are known as transaminases.
- Alkaline phosphatase (AP) and gammaglutamyl transferase (GGT) are known as cholestatic liver enzymes. If these enzymes are elevated it can indicate the presence of liver disease.
- Secretory enzymes are enzymes made in the liver and allocated to the blood plasma. Their role is physiological, for example, enzymes involved in blood clotting (AC globulin) or cholinesterase, which catalyzes the hydrolysis of acetylcholine. Damage to the liver will reduce their synthesis leading to a decrease in their enzyme activity.
AST and ALT
There are enzymes that enter into the blood from the tissues to perform intracellular functions. Some of the enzymes are in the cell cytosol, such as ALT, AST and LDH, and others are in the cell mitochondria, such as GGT and AP. Any damage to the liver will cause the enzymes from the cells to enter the blood and their activity will increase. Amounts of ALT and AST are the greatest diagnostic value. In parenchymatous hepatitis serum transaminase ALT increases, sometimes 100 times or more and AST to a lesser extent. In addition to the liver, AST enzymes can be found in the heart, muscle, brain and kidney and is released into blood serum when these tissues become damaged. For example, a heart attack or muscle disorders will increase AST serum levels. Because of this AST isn’t necessarily an indicator of liver damage.ALT is almost specifically found in the liver. After liver injury it’s released into the bloodstream and therefore can be used as a fairly specific indicator of liver function.
It’s common for high levels of AST and ALT in the liver to damage numerous liver cells, called hepatic necrosis and can lead to death of the cells. The higher the ALT levels the greater the amount of cell death. Despite this ALT’s aren’t always a good indicator of how well the liver is functioning. Only a liver biopsy can reveal this. Diseases that can cause increased levels of liver enzymes AST and ALT are acute viral hepatitis A or B, as well as toxins caused by acetaminophen overdose,or a prolonged collapse of the circulatory system, which is called shock. It deprives the liver of fresh blood that brings oxygen and nutrients. Transaminase levels can be 10 times the upper limit.
Sometimes elevated liver enzymes can be found in otherwise healthy individuals. In such cases they’re usually found to be twice the upper limit. Fatty liver is a common problem causing elevated liver enzymes. In the United States and other countries in the world the most frequent causes of fatty liver are alcohol and drug abuse, obesity, diabetes, and sometimes chronic hepatitis C.
Alkaline phosphatase is an enzyme that’s produced in the bile ducts, kidney, intestines, placenta and the bone. If this enzyme is high and ALT and AST levels are pretty normal there could be a problem with the bile duct such as an obstruction. Some bone disorders may also cause alkaline phosphatase levels to increase. If there is an elevation of alkaline phosphatase it could also indicate there is an injury to the biliary cells. This could be due to gallstones or certain medications. Under normal circumstances the enzyme is mainly allocated to the bile, but if pathology exists the norm is disturbed and the enzyme increases in blood plasma.
GGT is another enzyme that’s produced in the bile ducts and can become elevated if there is a problem with the bile ducts. High levels of GGT and AP indicate a possible blockage of the bile ducts or a possible injury or inflammation of the bile ducts. This problem is characterized by an impairment or failure of bile flow and is known as cholestasis and the term refers to bile duct blockage or injury within the liver. As a rule, intrahepatic cholestasis will occur in individuals with primary biliary cirrhosis or liver cancer. The term extrahepatic cholestasis refers to bile duct blockage or injury outside of the liver and may occur in individuals with gallstones.GGT and AP can seep out of the liver and into the bloodstream, but only with blockage or inflammation of the bile ducts. The enzymes will be about ten times the upper normal limit.Unlike AP, GGT is found predominantly in the liver. Taking this into account, GGT is a sensitive marker of alcohol ingestion and certain hepatotoxic (liver toxic) drugs, where is can be elevated without AP elevation. It’s unclear why, but cigarette smokers have a higher GGT and AP levels than nonsmokers. When testing levels of AP and GGT the levels will be most accurate after a 12 hour fast.
Nonalcoholic Fatty Liver
Normal levels of alkaline phosphatase range from 35 to 115 IU/Liter and the normal levels of GGT range from 3 to 60 IU/Liter. Causes of elevated AP and GGT are:
- Alcoholic liver disease
- Primary biliary cirrhosis
- Liver tumors
- Nonalcoholic fatty liver disease
- Primary sclerosing cholangitis
- Drugs that are used to treat liver disease
One study at the Mayo Clinic was conducted over ten years and determined that an excess of enzymes in the liver is associated with the risk of death. High levels of aspartate aminotransferase and alanine aminotransferase in the blood not only can develop into liver disease, but can also have a fatal outcome.
Stages of Liver Damage
A group of enzymes, that are located in the endoplasmic reticulum, known as cytochrome P-450, is the most important family of metabolizing enzymes found in the liver. Cytochrome P-450 is the terminal oxidase component of an electron transport chain. It’s not a single enzyme, but consists of a family of closely related 50 isoforms. Six of them metabolize 90% of drugs. There is a great diversity of individual P-450 gene products and this heterogeneity allows the liver to perform oxidation on a vast array of chemicals, which includes almost all drugs.
- oral contraceptives
- anabolic steroids
- chemotherapeutic drugs
Acetaminophen overdose is the most common cause of drug induced liver disease