Nitrogen metabolism and the urea cycle
Introducido| English | Significado |
|---|---|
| transamination | transamination |
| glutamate/ˈɡluːtəmeɪt/ | glutamate |
| urea cycle | urea cycle |
| glutamine | glutamine |
| alanine | alanine |
Nitrogen cannot be stored
- Every amino acid not needed today must be broken down today, and the ammonia it releases poisons the brain at micromolar levels.
- Disposal is not optional: it is a five-step conveyor that runs across two compartments of the liver cell.
Collecting the amino groups
- Transamination 转氨基作用 moves amino groups onto α-ketoglutarate: amino acid + α-ketoglutarate ⇌ keto acid + glutamate 谷氨酸.
- In liver mitochondria, oxidative deamination then frees the nitrogen from glutamate as NH₃, right where the urea cycle starts.
Alanine transaminates with α-ketoglutarate. What are the products?
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
The amino group moves to α-ketoglutarate, making glutamate; alanine's carbon skeleton is left as pyruvate.
The urea cycle
- The urea cycle 尿素循环 starts in the mitochondrion: NH₃ + CO₂ → carbamoyl phosphate → citrulline.
- In the cytosol: citrulline + aspartate → argininosuccinate → arginine → urea, and ornithine returns to start again.
Put the urea cycle intermediates in order, starting from ammonia.
Dificultad 3/5 · 200 monedas + un pequeño bono en el primer intento de hoy
The first two steps are in the mitochondrion; citrulline then moves to the cytosol for the rest.
Urea by the numbers
- Each urea carries 2 N: one from NH₃, one from aspartate. Making it costs 3 ATP, which is 4 high-energy bonds.
- Normal blood ammonia is only about 10–35 µmol per L, and it must stay that low because the brain has no urea cycle.
How many high-energy phosphate bonds does making one urea cost?
Dificultad 2/5 · 140 monedas + un pequeño bono en el primer intento de hoy
3 ATP are used, but one is split to AMP + PPi, which costs two bonds, so 4 bonds in total.
Why the liver, and the nitrogen taxis
- Blood from the gut goes straight to the liver through the portal vein, so the liver removes amino acids and ammonia before they reach the rest of the body.
- Other tissues send their nitrogen to the liver in safe forms: glutamine 谷氨酰胺 (carrying ammonia) and alanine 丙氨酸 (carrying nitrogen and carbon from muscle).
Match each molecule to its role in nitrogen transport.
Dificultad 2/5 · 140 monedas + un pequeño bono en el primer intento de hoy
Tissues ship nitrogen to the liver in non-toxic forms; the liver converts it to urea for the kidneys.
Worked example: the daily ledger
- A diet with about 90 g of protein a day holds about 14 g of N (protein is about 16% N). Almost all of it leaves as urea.
- Urea is 28 g of N in every 60 g, 47% N. So 14 g N ÷ 0.47 ≈ 30 g of urea a day, which matches what urine contains.
A patient eats 120 g of protein a day (16% N). If all the N leaves as urea (47% N), how many grams of urea is that?
Dificultad 2/5 · 140 monedas + un pequeño bono en el primer intento de hoy
120 × 0.16 = 19.2 g N, and 19.2 / 0.47 ≈ 41 g of urea a day.
Worked example: the blocked conveyor
- (Fictional newborn) Sleepy, then in a coma after the first feeds, with very high ammonia and orotic acid in the urine. Ornithine transcarbamylase (OTC), the cycle's second step, is missing.
- Carbamoyl phosphate cannot move on, so it spills into pyrimidine synthesis and makes orotic acid. Treatment follows the block: less nitrogen in, drugs that remove ammonia, and the missing products supplied.
Why is orotic acid high in the urine in OTC deficiency?
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
The block is right after carbamoyl phosphate, which then enters the pyrimidine pathway and makes orotate.
Three common slips
- "Urea removes ammonia." It removes two nitrogens: one from NH₃ and one from aspartate.
- Urea cycle in the brain. It runs only in the liver, which is why ammonia harms the brain.
- Free disposal. Each urea costs 4 high-energy bonds.
The brain can protect itself from ammonia by running its own urea cycle.
Dificultad 1/5 · 100 monedas + un pequeño bono en el primer intento de hoy
The urea cycle runs in the liver. The brain can only trap ammonia as glutamine, which is why high ammonia harms it.
Recap
- Transamination collects nitrogen on glutamate; the liver releases it as NH₃.
- The urea cycle spans mitochondrion and cytosol and costs 3 ATP per urea, removing 2 N.
- Glutamine and alanine carry nitrogen to the liver; high ammonia with orotic acid points to OTC.