Foundations · Year 1 · from Foundations
Case 2: Statin Therapy for Hypercholesterolemia (Competitive Enzyme Inhibition)
Clinical Image
Source: Wikipedia - Statin - Public Domain
Case Presentation
A 58-year-old woman with type 2 diabetes and hypertension presents for routine follow-up. Her fasting lipid panel reveals LDL cholesterol of 168 mg/dL (goal <70 for her risk profile), HDL 42 mg/dL, and triglycerides 180 mg/dL. She has a 10-year ASCVD risk score of 22%. After discussing lifestyle modifications including diet and exercise, she is started on atorvastatin 40 mg daily. At her 6-week follow-up, repeat lipid panel shows LDL cholesterol reduced to 85 mg/dL, a 49% reduction. She reports mild muscle aches that improve with continued use. She is counseled that statins competitively inhibit HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Because the inhibition is competitive, endogenous substrate (HMG-CoA) can still bind when inhibitor concentrations fall between doses, which is why consistent daily dosing is important. She tolerates therapy well and continues on this regimen.
Key Learning Points
- Statins are competitive inhibitors of HMG-CoA reductase that structurally resemble the enzyme's transition state intermediate
- Competitive inhibition increases apparent Km (more substrate needed to reach half-maximal velocity) but does not change Vmax (maximum velocity can still be achieved with sufficient substrate)
- On a Lineweaver-Burk plot, competitive inhibitors produce lines that intersect on the y-axis, reflecting unchanged Vmax but increased Km