Lipids, proteins, and diagnostic enzymes

Lipids, proteins, and enzymes give the board three rich veins of questions, and they reward pattern recognition more than memorization. If you know which lipoprotein carries what, how to split total protein into albumin and globulin, and which enzyme rises when a given organ is injured, you can reason your way through most items instead of guessing. This lesson turns those patterns into fast decisions.

Lipoproteins: who carries what

Cholesterol and triglycerides do not dissolve in plasma, so they travel packaged with protein as lipoproteins. Four classes matter, sorted by density.

• Chylomicrons are the largest and least dense. They carry mostly dietary triglyceride from the gut and cause the milky look of a very fatty specimen.
• Very low density lipoprotein (VLDL) carries mostly endogenous triglyceride made by the liver.
• Low density lipoprotein (LDL) is the major cholesterol carrier and the main atherogenic (artery-clogging) particle. This is the "bad" cholesterol.
• High density lipoprotein (HDL) is the smallest and densest, with the highest protein content. It carries cholesterol away from tissues back to the liver, so it is the "good", protective particle.

A memory hook: as density rises from chylomicrons to HDL, triglyceride content falls and protein content rises.

Worked example: the Friedewald LDL

Most labs estimate LDL rather than measure it, using the Friedewald equation. In mg/dL:

LDL = Total cholesterol − HDL − (Triglyceride / 5)

The triglyceride divided by 5 term estimates the cholesterol carried in VLDL. Suppose total cholesterol is 200 mg/dL, HDL is 50 mg/dL, and triglyceride is 150 mg/dL. Then VLDL cholesterol is 150 / 5 = 30, and LDL = 200 − 50 − 30 = 120 mg/dL.

Two cautions the board tests hard. First, the estimate needs a fasting specimen, because a recent meal inflates triglyceride. Second, the equation becomes unreliable and should not be used when triglyceride is very high (above roughly 4.5 mmol/L or 400 mg/dL), because the VLDL estimate breaks down. In SI units the VLDL term uses triglyceride divided by about 2.2 instead of 5.

Total protein, albumin, and globulin

Serum total protein is the sum of two fractions:

Total protein = Albumin + Globulins

• Albumin is the single most abundant plasma protein. It maintains oncotic (colloid osmotic) pressure and transports many substances (bilirubin, calcium, drugs, fatty acids). Low albumin causes edema and shifts the calcium picture.
• Globulins are a mixed group: alpha, beta, and gamma (the immunoglobulins). They rise in chronic inflammation and in conditions such as multiple myeloma.

You can always recover globulin by subtraction: Globulin = Total protein − Albumin. The albumin to globulin (A/G) ratio is albumin divided by globulin and is normally greater than 1. A reversed (low) A/G ratio points to either low albumin (liver disease, nephrotic loss) or high globulin (chronic inflammation, myeloma).

Worked example: A/G ratio

Total protein is 8.0 g/dL and albumin is 3.0 g/dL. Globulin = 8.0 − 3.0 = 5.0 g/dL, so the A/G ratio = 3.0 / 5.0 = 0.6. That reversed ratio flags either albumin loss or a globulin excess that deserves follow-up.

The diagnostic enzymes and their organ patterns

Enzymes leak into blood when the cells that hold them are damaged, so the pattern tells you which organ is hurt. Anchor each enzyme to its home tissue.

Enzyme	Chief source	What a rise suggests
ALT (alanine aminotransferase)	Liver	Hepatocellular injury; more liver-specific than AST
AST (aspartate aminotransferase)	Liver, heart, skeletal muscle	Liver or muscle injury; less specific
ALP (alkaline phosphatase)	Liver (bile ducts), bone	Cholestasis or bone (osteoblastic) activity
GGT (gamma-glutamyl transferase)	Liver, bile ducts	Confirms a hepatobiliary source; sensitive to alcohol
CK (creatine kinase)	Skeletal and cardiac muscle, brain	Muscle injury
CK-MB	Cardiac muscle	Myocardial injury (older cardiac marker)
LDH (lactate dehydrogenase)	Nearly all tissues	Nonspecific cell turnover or hemolysis
Amylase	Pancreas, salivary glands	Acute pancreatitis
Lipase	Pancreas	Acute pancreatitis; more specific, stays up longer
Troponin (I or T)	Cardiac muscle	The most sensitive and specific marker of myocardial infarction

Several high-yield relationships live inside this table:

• ALP plus GGT: if ALP is high, a high GGT confirms the liver or bile ducts as the source; a normal GGT with high ALP points instead to bone (or growing children and pregnancy). GGT is the tie-breaker.
• The De Ritis ratio is AST divided by ALT. In most acute hepatitis ALT exceeds AST (ratio below 1), while an AST that exceeds ALT (ratio above 1) is classic for alcoholic liver disease and cirrhosis.
• Cardiac markers: troponin has replaced CK-MB and LDH as the preferred marker of myocardial infarction because it is more sensitive and specific. CK-MB is still useful for detecting reinfarction.
• Pancreatitis: both amylase and lipase rise, but lipase is more specific to the pancreas and remains elevated longer, so it is more useful if the patient presents late.

Common traps

• Calling HDL the "bad" cholesterol. HDL is protective; LDL is the atherogenic one.
• Using the Friedewald equation on a non-fasting sample or when triglyceride is very high; both make the LDL estimate invalid.
• Forgetting that globulin is total protein minus albumin, not a directly reported number in a basic panel.
• Reading a high ALP as automatically liver in origin. Check GGT: normal GGT means think bone.
• Treating AST as liver-specific. It also rises with heart and skeletal muscle damage.
• Choosing amylase over lipase as the more specific and longer-lasting pancreatic marker.

Recap

Density rises and triglyceride falls as you move from chylomicrons to VLDL to LDL to HDL, with LDL the main cholesterol carrier and HDL the protective one. Estimate LDL with Friedewald on a fasting sample, and abandon the equation when triglyceride is very high. Total protein splits into albumin and globulin, with globulin found by subtraction and the A/G ratio normally above 1. For enzymes, match the pattern to the organ: ALT and AST for liver, ALP with GGT for cholestasis versus bone, CK and troponin for heart and muscle, and lipase over amylase for the pancreas.