Urea Cycle Tournament
Two onboarding diagrams orient you in amino-acid catabolism + nitrogen handling. Then eight MCAT-DoK quiz rounds: CPS I as the rate-limiting enzyme, OTC deficiency vs. citrullinemia, the 4-ATP cost per urea, NAG as obligate activator, hepatic encephalopathy mechanisms, and ammonia scavenger pharmacology.
Where the Urea cycle fits in Metabolism of amino acids & derivatives
The urea cycle is the liver's nitrogen-disposal machine. Free NH3 (from amino acid catabolism) plus aspartate-N condense across mitochondrial and cytosolic enzymes to form urea, which is excreted in urine. Click the highlighted Urea cycle box to enter the tournament.
Click the highlighted Urea cycle 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 the urea cycle inside amino-acid metabolism on the live Reactome map.
Whole-Pathway Overview
Pan and zoom the curated WikiPathways urea cycle figure before you start answering.
Fill in the Blank
Recall CPS I as the rate-limiting urea-cycle enzyme; activated by NAG; uses free NH3 + 2 ATP.
Disruptor
Diagnose OTC deficiency from hyperammonemia + orotic aciduria + low citrulline.
Sequence Ordering
Trace carbamoyl phosphate -> citrulline -> argininosuccinate -> arginine -> urea + ornithine.
Match the Pairs
Pair each urea-cycle enzyme with its cellular compartment + key reaction feature.
Numeric Input
Count the 4 ATP equivalents spent per urea (2 at CPS I + 2 at ASS).
Select All That Apply
Identify TRUE statements about ammonia transport (glutamine, alanine), liver-only urea synthesis, and astrocyte α-KG depletion.
Odd One Out
Distinguish glutamine (CPS II / pyrimidine substrate) from urea-cycle intermediates.
Pharmacology Fill-in
Recall sodium phenylbutyrate / benzoate as the textbook ammonia scavengers for inborn urea-cycle defects.
Public leaderboard
Your score posts to a global, persistent leaderboard scored by points first, time as tiebreaker.
Urea cycle in 60 seconds
The urea cycle is essentially liver-only. It packages two nitrogens (one from free NH3, one from aspartate) plus a CO2 into urea, which is freely water-soluble and renally excreted. The cycle straddles two compartments: mitochondrion (CPS I + OTC) and cytosol (the rest).
Rate limiting and committed: CPS I. Obligate activator: N-acetylglutamate (NAG), made by NAG synthase whenever arginine is abundant - so a high-protein meal directly throttles up urea synthesis. Distinguish CPS I (mitochondrial, uses NH3) from CPS II (cytosolic, uses glutamine, pyrimidine pathway).
Each urea costs ~4 ATP equivalents: 2 at CPS I, 2 at ASS (the ATP -> AMP + PPi step counts as 2 because PPi -> 2 Pi forces extra ATP regeneration). The fumarate released by ASL re-enters the TCA, linking nitrogen disposal to energy metabolism.
Defects are devastating in newborns. OTC deficiency is X-linked and uniquely shows orotic aciduria (carbamoyl phosphate spills to the cytosol -> pyrimidine pathway). Treatment of severe defects: low-protein diet, arginine supplementation, and ammonia scavengers (phenylbutyrate, benzoate) that conjugate amino acids and provide an alternative nitrogen excretion route.
FAQ
Why does the urea cycle live almost exclusively in the liver?
All five cycle enzymes co-localize in periportal hepatocytes, and the liver receives the bulk of nitrogen-laden plasma (glutamine + alanine) from peripheral tissues via the portal circulation. The kidney can detoxify ammonia locally as glutamine -> NH4+ but does NOT make urea de novo.
Why is hyperammonemia neurotoxic?
Astrocytes consume NH3 by glutamate -> glutamine (glutamine synthetase, ATP-dependent). This depletes α-ketoglutarate (slowing the TCA cycle) AND increases intracellular osmolarity (cerebral edema). Both effects converge on encephalopathy.
What is the difference between CPS I and CPS II?
CPS I = mitochondrial, uses free NH3, urea cycle, NAG-dependent. CPS II = cytosolic, uses glutamine's amide N, pyrimidine biosynthesis, NAG-independent (regulated by ATP/UTP feedback).
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
PKU, alkaptonuria, MSUD, homocystinuria - where amino acid carbons end up.
Aspartate / fumarate cycling between the urea cycle and TCA hooks straight into gluconeogenesis.
Overview diagram: Reactome Pathway R-HSA-71291, licensed CC BY 4.0.