33 - Metabolism of ammonia – generation, toxicity, ammonia detoxification: reductive amination of alpha-ketoglutarate, glutamine synthesis, role of ammoniagenesis in kidney. Urea cycle – regulation, metabolic disorders. Glucose-alanine cycle.

sections

• production

• ammonia detoxification

• location

• urea cycle

• glutamine synthesis

• role of liver + muscle

• oral box

• production

• derives from metabolism of AAs

• transamination + deamination produces ammonia

• ammonia detoxification

• Ammonia si weak toxic base so needs to be detoxified/eliminated from body

• done by circulation in liver to convert to urea

• Toxic to CNS as reacts with alpha-KG to make glutamate

• Depleted levels of alpha-KG leads to impairment of TCA

• Location

1. liver → urea cycle

2. Brain → hepatic encephalopathy

• urea cycle

• requires glutamate dehydrogenase reaction

• Uses NAD/NADP to release nitrogen as ammonia

• glutamine synthesis

• fixes ammonia or glutamate and is catalysed by glutamine synthase

• ammonia detoxified by ammoniagenesis:

  • by kidney as response to alkalosis

  • more bicarbonate secreted = lower glutamine metabolism + ammonia excretion

  • NH4+ produced in proximal tubules

• role of liver + muscle

• free AAs, alanine + glutamine are released from muscle into circulation

• Alanine extracted by liver

• glutamine → gut + kidney

• glutamine is source of ammonia for excretion by kidney

• oral box