Enzymes And Heme Derivatives

Cardiac enzymes and markers

The MLS exam loves enzyme time-course questions. Cardiac troponin I and T (cTnI/cTnT) are the gold-standard markers for acute myocardial infarction (AMI): they begin to rise 3-6 hours after symptom onset, peak around 12-24 hours, and remain elevated 7-14 days. High-sensitivity troponin assays detect injury even earlier. CK-MB (creatine kinase MB isoenzyme) rises 4-6 hours, peaks ~24 hours, and returns to baseline in 48-72 hours -- that quick return makes CK-MB useful for detecting reinfarction. Myoglobin is the earliest marker (1-3 hours) but is nonspecific. Older LDH flip (LDH-1 > LDH-2) is now obsolete.

CK isoenzymes: CK-MM (skeletal muscle, ~98%), CK-MB (cardiac), CK-BB (brain). A high total CK with elevated CK-MM and no MB points to rhabdomyolysis, not MI.

Liver and pancreatic enzymes

ALT (alanine aminotransferase) is more liver-specific than AST (aspartate aminotransferase), which also appears in heart and muscle. In viral hepatitis, ALT > AST; in alcoholic liver disease the AST:ALT ratio is > 2:1 (the De Ritis ratio). Both transaminases use pyridoxal-5-phosphate as a coenzyme.

Alkaline phosphatase (ALP) rises in cholestasis and bone disease. To localize the source, pair it with GGT (gamma-glutamyl transferase): high ALP + high GGT = hepatobiliary/obstruction; high ALP + normal GGT = bone (Paget disease, healing fracture, growing children). GGT is also a sensitive marker of alcohol use.

Amylase and lipase rise in acute pancreatitis; lipase is more specific and stays elevated longer (up to 8-14 days) while amylase normalizes faster and is also raised by salivary disease and macroamylasemia.

Heme derivatives: bilirubin and porphyrins

Heme catabolism produces bilirubin. Always fractionate. Unconjugated (indirect) bilirubin is fat-soluble, albumin-bound, and rises in prehepatic/hemolytic jaundice and neonatal physiologic jaundice. Conjugated (direct) bilirubin is water-soluble, appears in urine, and rises in posthepatic/obstructive disease. The diazo (Jendrassik-Grof) method measures total and direct; subtract for indirect.

• Crigler-Najjar / Gilbert: unconjugated rises (UGT deficiency)
• Dubin-Johnson: conjugated rises (excretion defect)
• Neonatal bilirubin > ~15-20 mg/dL risks kernicterus -> phototherapy

Porphyrias result from defective heme-synthesis enzymes; acute intermittent porphyria shows elevated urine porphobilinogen (PBG) and delta-aminolevulinic acid (ALA). Lead poisoning inhibits ALA dehydratase and ferrochelatase, raising free erythrocyte protoporphyrin (FEP) and zinc protoporphyrin.

Enzyme kinetics and reporting

Understand how enzymes are measured because procedural items test it. Enzymes are reported in activity units (U/L), not mass, and most clinical enzyme assays operate in zero-order kinetics -- substrate is in excess so the rate depends only on enzyme concentration. The optimal reaction conditions (pH, temperature, coenzyme) must be controlled; a temperature shift changes the measured rate, so assays are run at a defined temperature (commonly 37 C). Many assays couple to NAD(P)/NAD(P)H and read the change in absorbance at 340 nm (the wavelength where NADH absorbs but NAD+ does not).

Hemolysis falsely raises LDH, AST, and potassium because they are concentrated inside red cells -- a critical preanalytical trap on enzyme panels.

Putting enzyme patterns together

A patient with right-upper-quadrant pain, a markedly high ALP and GGT, elevated conjugated bilirubin, and only modestly raised transaminases fits biliary obstruction. Contrast that with very high ALT and AST (in the thousands) and a high indirect-and-direct bilirubin in acute viral hepatitis, where ALT exceeds AST. A patient three hours into crushing chest pain with a normal early troponin should not be cleared -- serial troponins at 3-6 hours are required because the marker has not yet risen. These integrated pictures, not single values, are what the exam rewards.

Pancreatic, renal, and other diagnostic enzymes

Beyond cardiac and hepatic panels, know the supporting enzymes. Acid phosphatase (prostatic fraction) was a historical prostate marker now replaced by PSA. Cholinesterase (pseudocholinesterase) is decreased in organophosphate poisoning and in patients who cannot metabolize the anesthetic succinylcholine. 5'-nucleotidase confirms a hepatobiliary source for an elevated ALP when GGT is ambiguous. Aldolase parallels CK in muscle disease.

For pancreatitis, the lipase-to-amylase ratio helps distinguish alcoholic from non-alcoholic causes, and macroamylasemia (amylase bound to immunoglobulin) produces a persistently high serum amylase with a low urine amylase because the large complex is not filtered -- a classic correlation that explains an otherwise puzzling result. Always pair an isolated enzyme elevation with a confirming second analyte: ALP with GGT or 5'-NT, amylase with lipase, and total CK with CK-MB. Treating any single enzyme as diagnostic in isolation is the error these items are designed to expose.

Bilirubin handling and neonatal correlations

Bilirubin specimens must be protected from light, because exposure can lower the measured value by 30-50% per hour through photo-oxidation; this is the same chemistry exploited by neonatal phototherapy, which converts unconjugated bilirubin to water-soluble isomers for excretion. In a newborn, physiologic jaundice appears after 24 hours and is unconjugated, whereas jaundice within the first 24 hours suggests pathologic hemolytic disease of the newborn and demands urgent evaluation. A rising conjugated bilirubin in an infant instead suggests biliary atresia or a metabolic disorder, never simple physiologic jaundice.

Knowing that the diazo reaction reports total and direct, with indirect obtained by subtraction, and that delta-bilirubin (albumin-bound conjugated bilirubin) can keep total bilirubin elevated during recovery from obstruction, lets you reconcile a panel where the direct fraction stays high after the obstruction resolves -- a subtle correlation the exam occasionally tests.