Enzymes and Clinical Conditions

• Enzymes are protein catalysts that speed up reactions without being altered in the process.
• A substrate is the substance upon which an enzyme acts; for instance, lactose is the substrate for the lactase enzyme.

Substrate Binding Site

• A specific pocket or cleft on the enzyme's surface where the substrate binds.

Isoenzymes (Isozymes)

• Different forms of the same enzyme, possessing the same catalytic activity but differing in chemical, immunological structure, and tissue sources.

Nomenclature (Terminology)

• Some enzymes retain common names like trypsin and pepsin.
• Most enzyme names use the suffix "-ase."
• The "-ase" suffix is attached to the substrate of the reaction, such as glucosidase acting on glucose, or to a description of the action performed, like lactate dehydrogenase.

General Properties

• Enzymes are proteins, making them water-soluble.
• Enzymes are denatured by increased temperature (heat labile), concentrated salt solutions, and extreme pH levels.
• They require optimal temperature and pH for maximal activity.
• Enzymes are specific in their action, typically acting on one or two substrates.
• Enzymes remain chemically unchanged during a reaction.

Classification of Enzymes

Functional Plasma Enzymes Characteristics:

• Having a specific function in the blood.
• Present at all times in plasma.
• Present in higher concentrations in the blood than in tissues.
• Often synthesized in the liver.
• Their substrates are present in the blood.
• Examples include lipoprotein lipase, coagulation factors, and fibrinolytic enzymes.

Non-Functional Plasma Enzymes Characteristics:

• Having no specific function in the blood.
• Their substrates are absent from the blood.
• Function mainly intracellularly.
• Present in the blood in very small concentrations compared to tissue levels.
• Their levels increase in plasma during cellular damage; examples include AST, ALT, CK, and ALP.

Examples of Clinically Important Enzymes and Isoenzymes:

• Serum Aspartate aminotransferase (AST or GOT).
• Alanine transaminase (ALT or GPT).
• Alkaline phosphatase.
• Creatine kinase (CPK or CK) and its isoenzyme MB.
• Lactate dehydrogenase (LDH) and its isoenzymes (LDH1 and LDH2).

Aspartate Transaminase (AST or GOT)

• Found in high concentrations in the cytosol and mitochondria of cardiac and skeletal muscle cells, with lesser concentrations in the liver, kidney, and erythrocytes.
• It has two isomers: one in the cytosol and one in the mitochondria.
• The normal serum level of AST is 5-35 U/L.
• AST catalyzes: Aspartate + α Ketoglutarate → oxaloacetate + glutamic acid

Causes For Increased AST

• Myocardial infarction, although it is nonspecific.
• Acute viral or toxic hepatitis.
• AST is more specific for heart diseases such as myocardial infarction.

Alanine Transaminase (ALT old name is GPT)

• ALT is an intracellular enzyme present in the cytosol of cells; it is found in high concentrations in liver cells and to a lesser extent in skeletal muscles, kidneys, and the heart.
• Normal ALT levels range from 5-40 IU/L.
• ALT catalyzes: Alanine + α Ketoglutarate → Pyruvate + glutamate

Causes For Increased ALT

• Acute viral or toxic hepatitis.
• Cirrhosis (may be normal).
• Liver congestion secondary to congestive heart failure.
• ALT is more specific for liver diseases than AST.

Alkaline Phosphatase

• It is a hydrolase enzyme responsible for removing phosphate from chemical compounds.
• The optimal activity of Alkaline Phosphatase is at pH 8.
• It is secreted in different organs, including the intestine, kidney, bone, liver, and placenta.

Causes of Raised Plasma Alkaline Phosphatase Activity:

Physiological Reasons:

• During the last trimester of pregnancy, plasma total ALP activity increases due to the placental isoenzyme.
• In preterm infants, plasma total ALP activity can be up to five times higher.
• In children, total activity is roughly 2.5 times higher due to increased osteoblastic activity.

Pathological Reasons:

• Jaundice from extrahepatic obstruction.
• Intrahepatic cholestasis.
• Infective hepatitis.
• Alcoholic hepatitis.
• Hepatocellular carcinoma.

Dramatically High ALP Levels (25 Times the Upper Limit):

• Bone diseases such as Paget's disease.
• Rickets and osteoblastoma.
• Metastatic carcinoma of bone and in hyperparathyroidism.

Creatine Phosphokinase (CPK or CK):

• Found in the heart, brain, and skeletal muscles.
• Creatine + ATP → Creatine phosphate + ADP

Isoenzymes of CPK:

• It consists of two subunits, M and B, which combine to form three isoenzymes: CK-MM, CK-MB, and CK-BB.
• CK-MM is the predominant isoenzyme in skeletal and cardiac muscle and is found in the plasma of healthy individuals.
• CK-MB is derived from the heart muscle and makes up less than 5% of skeletal muscles.
• CK-MB has two isoforms: CK-MB1 and CK-MB2.
• CK-BB is in high concentrations in the the brain, the smooth muscles of the gastrointestinal and genital tracts.

Conditions With Raised Creatine Kinase:

• Creatine kinase levels significantly increase when injury, inflammation, or necrosis of skeletal or heart muscles occurs.
• CK-MM increases in muscle dystrophy.
• CK-MB increases in myocardial infarction.
• CK-BB increases in brain cancer and brain injury.

Lactate Dehydrogenase (LDH)

• Catalyzes the conversion of pyruvate to lactate and vice versa in different tissues.
• Widely distributed with high concentrations in the liver, heart, skeletal muscles, kidney, brain, and erythrocytes.
• The reference range for total LDH is 100-200 U/L.
• LDH is composed of 4 subunits (tetramer) of H and M subunits.
• There are 5 isoenzymes:
  • LDH-1 (4H): in the heart.
  • LDH-2 (3H1M): in the reticuloendothelial system.
  • LDH-3 (2H2M): in the lungs.
  • LDH-4 (1H3M): in the kidneys.
  • LDH-5 (4M): in the liver and striated muscle.

Causes For Increased LDH

• Myocardial infarction.
• Viral hepatitis.
• Skeletal muscle diseases.
• Elevation of LDH-5 indicates damage to the liver or skeletal muscle. When LDH-1 is higher than LDH-2, myocardial infarction is likely. LDH will increase 6-12 hours after myocardial infarction, peaking at 24-48 hours, and returning to normal in 6-8 days.

A quiz focusing on enzymes, their function, and clinical significance, covering topics such as AST levels, enzyme specificity, isoenzymes, enzyme denaturation and alkaline phosphatase activity in various conditions like jaundice and myocardial infarction. Assesses understanding of enzyme characteristics and their role in diagnosing diseases.