Heme Biosynthesis & Porphyrias Tournament
Two onboarding diagrams orient you in heme biosynthesis. Then eight MCAT-DoK quiz rounds: ALA synthase as rate-limiting (B6 cofactor), the cytosol-to-mitochondrion shuttle, lead's dual block (ALA dehydratase + ferrochelatase), AIP triggers (P450 inducers), PCT phototoxicity, ALAS1 vs ALAS2 regulation, and bilirubin's downstream story.
Where the Metabolism of porphyrins fits in Whole-cell metabolism overview
Heme biosynthesis is an 8-step ring assembly that alternates between mitochondrion (start, end) and cytosol (middle four steps). Eight porphyrin intermediates, eight enzymes, eight clinical syndromes when one breaks. Click the highlighted Metabolism of porphyrins box to enter the tournament.
Click the highlighted Metabolism of porphyrins 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 heme biosynthesis inside whole-cell metabolism on the live Reactome map.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways heme biosynthesis figure before you start answering.
Fill in the Blank
Recall ALA synthase as the rate-limiting + committed mitochondrial enzyme (uses B6).
Disruptor
Diagnose lead poisoning from microcytic anemia + basophilic stippling + elevated zinc protoporphyrin.
Sequence Ordering
Trace the 8 enzyme steps with their cytosol / mitochondrion compartmentalization.
Match the Pairs
Pair each porphyria (AIP, PCT, hereditary copro, variegate, EPP, sideroblastic) with its deficient enzyme.
Numeric Input
Recall 8 ALA molecules per heme (4 PBG x 2 ALA each).
Select All That Apply
Identify TRUE facts about heme feedback, ALAS2 iron sensing, P450 inducers, and CO production by heme oxygenase.
Odd One Out
Distinguish mevalonate (cholesterol pathway) from heme intermediates ALA, PBG, protoporphyrin IX.
AIP Trigger Disruptor
Predict why phenobarbital precipitates an AIP attack via P450-induced heme depletion + ALAS1 release.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
Heme biosynthesis in 60 seconds
Heme is built from 8 succinyl-CoA + 8 glycine in 8 enzymatic steps, alternating between mitochondrion (start, end) and cytosol (middle four). Iron is slotted in at the very last step by ferrochelatase.
Rate limiting + committed: ALA synthase (B6 cofactor). Two isoforms: ALAS1 (ubiquitous, feedback-inhibited by heme) and ALAS2 (erythroid, regulated by iron via the iron-responsive element / IRP system).
Each enzyme block is associated with a distinct porphyria. AIP (PBG deaminase) = neurovisceral attacks (abdominal pain, neuropathy, psychiatric) precipitated by P450 inducers, fasting, alcohol. PCT (uroporphyrinogen decarboxylase) = adult-onset photosensitivity with blistering. EPP (ferrochelatase) = childhood photosensitivity.
Lead poisoning hits two enzymes at once - ALA dehydratase (cytosolic) + ferrochelatase (mitochondrial). Result: microcytic anemia, basophilic stippling, abdominal pain, peripheral neuropathy, elevated zinc protoporphyrin (Fe2+ can't be inserted, Zn2+ goes in instead). Treatment: chelation (succimer, EDTA, dimercaprol).
FAQ
Why does AIP cause neurologic symptoms?
δ-ALA accumulates upstream of the broken hydroxymethylbilane synthase. ALA structurally resembles GABA and is thought to be neurotoxic at high concentrations - causing the abdominal pain, peripheral neuropathy, autonomic symptoms, and psychiatric features.
Why does PCT respond to phlebotomy?
PCT is unmasked when iron overload increases hepatocyte oxidative stress, inhibiting uroporphyrinogen decarboxylase. Phlebotomy depletes iron stores, restoring some enzyme activity. Hydroxychloroquine works by mobilizing porphyrins from the liver into urine for excretion.
What does heme oxygenase do?
Heme oxygenase cleaves heme's α-methene bridge to produce biliverdin + Fe2+ + CO. Biliverdin reductase makes bilirubin, which is conjugated to glucuronate by UGT1A1 and excreted in bile. CO acts as a vasodilator at endogenous concentrations.
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
Different starting carbons + cofactor logic - the two great ring assembly pathways of biochemistry.
Where succinyl-CoA comes from before it's siphoned off to make heme.
Overview diagram: Reactome Pathway R-HSA-1430728, licensed CC BY 4.0.