Cholesterol Biosynthesis & Statins Tournament
Two onboarding diagrams orient you in lipid metabolism + sterol biosynthesis. Then eight MCAT-DoK quiz rounds: HMG-CoA reductase as the rate-limiting + statin target, the mevalonate -> IPP -> FPP -> squalene -> lanosterol path, why statins upregulate LDLRs, the 18-acetyl-CoA arithmetic of cholesterol carbons, AMPK regulation, and familial hypercholesterolemia.
Where the Metabolism of steroids fits in Metabolism of lipids
Cholesterol biosynthesis is a 27-step run from acetyl-CoA to a 27-carbon sterol, regulated by SREBP-2 sterol sensing and HMG-CoA reductase activity. It feeds membrane biogenesis, bile acid synthesis, steroid hormones, and vitamin D. Click the highlighted Metabolism of steroids box to enter the tournament.
Click the highlighted Metabolism of steroids box to continue.
What this tournament tests
Each task maps to a distinct MCAT cognitive demand. The first two orient you in the broader topology; the next eight test the high-yield mechanism, regulation, sequence and quantitative reasoning that consistently appear on test day.
The Bigger Picture
Anchor sterol biosynthesis inside lipid metabolism on the live Reactome overview map.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways cholesterol biosynthesis figure before you start answering.
Fill in the Blank
Recall HMG-CoA reductase as rate-limiting + the statin target; uses 2 NADPH.
Disruptor
Predict why statins lower LDL via LDLR upregulation, not just cholesterol-synthesis suppression.
Sequence Ordering
Trace acetyl-CoA -> HMG-CoA -> mevalonate -> IPP -> FPP -> squalene -> lanosterol -> cholesterol.
Match the Pairs
Pair each cholesterol-lowering drug class (statins, ezetimibe, sequestrants, PCSK9i, niacin) with its target.
Numeric Input
Count 18 acetyl-CoA per cholesterol (C27 from squalene C30 minus 3 lost methyls).
Select All That Apply
Identify TRUE facts about SREBP-2 retention, AMPK phosphorylation, 7α-hydroxylase, and de novo synthesis.
Odd One Out
Distinguish heme B (porphyrin pathway) from CoQ10, vitamin D, and farnesylated heme A (mevalonate-derived).
Familial Hypercholesterolemia Disruptor
Recognize LDLR mutations as the most common Mendelian dyslipidemia.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
Cholesterol biosynthesis in 60 seconds
Cholesterol's 27 carbons all come from acetyl-CoA, condensed in stages: 2 -> HMG-CoA (6) -> mevalonate (6) -> IPP (5) -> FPP (15) -> squalene (30) -> lanosterol -> cholesterol (27). The committed step is HMG-CoA reductase, the famous statin target.
Two parallel regulatory layers: SREBP-2 (transcription) senses ER cholesterol; when low, SREBP-2 is cleaved and translocates to the nucleus to upregulate HMG-CoA reductase AND LDL receptors. AMPK phosphorylates and inhibits HMG-CoA reductase under low ATP - the cell does not waste energy on cholesterol when it lacks energy.
Statins work mainly via LDLR upregulation: they modestly suppress cholesterol synthesis, the cell senses low sterol, SREBP-2 fires, and the LDLR pool expands - which clears LDL out of the plasma. PCSK9 inhibitors prevent LDLR degradation and amplify this effect.
Branch points off the mevalonate pathway feed CoQ10, dolichol, prenylated proteins (Ras, Rab), heme A's farnesyl side chain, and vitamin D. Statin myopathy may relate to CoQ10 depletion. Bisphosphonates inhibit FPP synthase and disrupt protein prenylation in osteoclasts.
FAQ
Why does HMG-CoA reductase have to be in the ER membrane?
The enzyme spans the ER bilayer with a sterol-sensing domain that triggers ubiquitination + proteasomal degradation when sterol is high. This compartmentalized control - separate from cytosolic HMG-CoA synthase - lets the cell coordinate cholesterol synthesis with membrane sterol content directly.
How does ezetimibe complement statins?
Ezetimibe blocks intestinal NPC1L1, reducing dietary + biliary cholesterol absorption. Statins suppress hepatic synthesis. Combining both eliminates the compensatory increase in absorption seen with statin monotherapy, producing additive LDL reductions of ~25% on top of statin alone.
Why do bisphosphonates cause jaw osteonecrosis?
Bisphosphonates inhibit FPP synthase, depleting prenylation substrates needed for small GTPase function (Ras, Rho) in osteoclasts. The bone of the jaw, with high turnover, is most vulnerable - rare but well-described complication of long-term bisphosphonate use.
Do I need an account to play?
No. The tournament is fully public. You get a randomized handle and your score posts to the public leaderboard at the bottom of this page.
Keep going
Both pathways start from cytosolic acetyl-CoA + NADPH; both hit the SREBP-1/2 transcription axis.
Different starting carbons (succinyl-CoA + glycine), different cofactor logic, but both classic biochemistry pathways.
Overview diagram: Reactome Pathway R-HSA-556833, licensed CC BY 4.0.