Physiology

Enzyme activity is crucial for maintaining cellular functions, and deviations from normal levels can indicate a range of diseases

Normal States

Balanced Enzyme Activity: Enzyme levels and activity are tightly regulated to maintain homeostasis
Cellular Compartmentalization: Enzymes are localized to specific cellular compartments to ensure proper function

Appropriate levels of enzymes are present in cells and body fluids to catalyze biochemical reactions efficiently
Enzyme activity is regulated by substrate concentration, pH, temperature, inhibitors, and activators
Enzyme synthesis and degradation are balanced to maintain a constant enzyme concentration
Enzymes are localized to specific cellular compartments to ensure proper function

Enzymes involved in specific metabolic pathways are localized to specific cellular compartments (e.g., mitochondria, endoplasmic reticulum, cytosol)
Compartmentalization ensures that reactions occur efficiently and in a coordinated manner
Compartmentalization also prevents enzymes from interfering with other cellular processes
Examples:
- Enzymes of glycolysis are located in the cytosol
- Enzymes of the Krebs cycle are located in the mitochondria
- Enzymes of fatty acid synthesis are located in the cytosol
- Enzymes of the electron transport chain are located in the inner mitochondrial membrane

Enzyme Deficiencies: Genetic defects leading to reduced or absent enzyme activity
Enzyme Elevations: Increased enzyme levels in blood due to tissue damage or disease
Isoenzyme Variations: Abnormal distribution of isoenzymes
Enzyme Inhibitions: Inhibition of enzyme activity by drugs, toxins, or metabolic disorders

Definition: Genetic disorders caused by mutations in genes encoding enzymes, leading to reduced or absent enzyme activity
Pathophysiology: Enzyme deficiencies disrupt metabolic pathways, leading to the accumulation of substrates and/or the deficiency of products
Laboratory Findings: Reduced or absent enzyme activity in affected tissues
Symptoms: Varies depending on the specific enzyme deficiency and the metabolic pathway affected
Examples
- Phenylketonuria (PKU): Deficiency in phenylalanine hydroxylase (PAH)
  - Elevated phenylalanine levels in blood
  - Intellectual disability, seizures
- Galactosemia: Deficiency in galactose-1-phosphate uridyltransferase (GALT)
  - Elevated galactose levels in blood and urine
  - Liver damage, cataracts, intellectual disability
- Tay-Sachs Disease: Deficiency in hexosaminidase A
  - Accumulation of gangliosides in nerve cells
  - Neurological deterioration, seizures, blindness
- Gaucher Disease: Deficiency in glucocerebrosidase
  - Accumulation of glucocerebrosides in macrophages
  - Splenomegaly, hepatomegaly, bone pain
- Lesch-Nyhan Syndrome: Deficiency in hypoxanthine-guanine phosphoribosyltransferase (HGPRT)
  - Elevated uric acid levels in blood and urine
  - Neurological dysfunction, self-mutilation
- Severe Combined Immunodeficiency (SCID): Deficiency in adenosine deaminase (ADA)
  - Accumulation of deoxyadenosine in lymphocytes
  - Impaired immune function, increased susceptibility to infections

Definition: Increased enzyme levels in blood, indicating tissue damage or disease
Pathophysiology: Tissue damage or disease causes the release of enzymes from cells into the bloodstream
Laboratory Findings: Elevated enzyme levels in blood
Symptoms: Varies depending on the specific enzyme and the tissue affected
Examples
- Myocardial Infarction (Heart Attack): Elevated troponin, creatine kinase (CK), and CK-MB
  - Chest pain, shortness of breath
- Hepatitis: Elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
  - Fatigue, jaundice, abdominal pain
- Pancreatitis: Elevated amylase and lipase
  - Abdominal pain, nausea, vomiting
- Prostate Cancer: Elevated prostate-specific antigen (PSA)
  - Urinary symptoms, bone pain
- Muscular Dystrophy: Elevated creatine kinase (CK)
  - Muscle weakness, muscle wasting

Definition: Abnormal distribution of isoenzymes, indicating tissue-specific damage or disease
Pathophysiology: Different tissues express different isoenzymes of certain enzymes. Measuring the levels of these isoenzymes can help identify the source of tissue damage
Laboratory Findings: Altered ratios of isoenzymes
Symptoms: Varies depending on the specific isoenzyme and the tissue affected
Examples
- Creatine Kinase (CK) Isoenzymes:
  - CK-MM: Found primarily in skeletal muscle
  - CK-MB: Found primarily in heart muscle
  - CK-BB: Found primarily in brain and smooth muscle
  - Elevated CK-MB suggests myocardial damage
- Lactate Dehydrogenase (LDH) Isoenzymes:
  - LDH-1: Found primarily in heart and red blood cells
  - LDH-2: Found primarily in heart and red blood cells
  - LDH-3: Found primarily in lung and other tissues
  - LDH-4: Found primarily in liver and muscle
  - LDH-5: Found primarily in liver and muscle
  - Elevated LDH-1 and LDH-2 suggest myocardial damage or hemolysis
  - Elevated LDH-5 suggests liver damage or muscle damage
- Alkaline Phosphatase (ALP) Isoenzymes:
  - Liver ALP: Found primarily in liver
  - Bone ALP: Found primarily in bone
  - Intestinal ALP: Found primarily in intestine
  - Elevated liver ALP suggests liver disease or biliary obstruction
  - Elevated bone ALP suggests bone disease

Definition: Inhibition of enzyme activity by drugs, toxins, or metabolic disorders
Pathophysiology: Inhibitors bind to enzymes, preventing them from catalyzing reactions
Laboratory Findings: Decreased enzyme activity
Symptoms: Varies depending on the specific enzyme and the metabolic pathway affected
Examples
- Cyanide Poisoning: Cyanide inhibits cytochrome oxidase, an enzyme in the electron transport chain
  - Cellular respiration is inhibited, leading to rapid death
- Organophosphate Poisoning: Organophosphates inhibit acetylcholinesterase, an enzyme that breaks down acetylcholine
  - Acetylcholine accumulates, leading to muscle paralysis and respiratory failure
- Methanol Poisoning: Methanol is metabolized to formaldehyde and formic acid, which inhibit cytochrome oxidase
  - Cellular respiration is inhibited, leading to metabolic acidosis, blindness, and death
- Warfarin Therapy: Warfarin inhibits vitamin K epoxide reductase, an enzyme required for the synthesis of clotting factors
  - Blood clotting is inhibited, preventing thrombosis
- Statins: Statins inhibit HMG-CoA reductase, an enzyme in cholesterol synthesis
  - Cholesterol synthesis is reduced, lowering LDL cholesterol levels

Enzyme Deficiency: Genetic disorder with reduced or absent enzyme activity
Enzyme Elevation: Increased enzyme levels in blood
Isoenzyme: Different forms of the same enzyme, with tissue-specific distribution
Enzyme Inhibition: Reduced enzyme activity due to inhibitors
Phenylketonuria (PKU): Deficiency in phenylalanine hydroxylase
Galactosemia: Deficiency in galactose-1-phosphate uridyltransferase
Myocardial Infarction: Heart attack
Hepatitis: Inflammation of the liver
Pancreatitis: Inflammation of the pancreas
Prostate Cancer: Cancer of the prostate gland
Muscular Dystrophy: A group of genetic disorders that cause progressive muscle weakness and loss
Isoenzymes: Different forms of the same enzyme, with tissue-specific distribution