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Biochemistry · Amino acid metabolism: ammonia and the brain
Sample itemA man with decompensated cirrhosis has confusion and a flapping tremor with a blood ammonia level three times normal. Which process in the brain contributes most to the cerebral swelling in this condition?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
B. Astrocytic glutamine accumulation from ammonia and glutamate, causing osmotic swelling
The brain has no urea cycle, so ammonia is detoxified in astrocytes by glutamine synthetase, which combines ammonia with glutamate in an ATP-requiring reaction. Glutamine is osmotically active and its accumulation causes astrocyte swelling and cerebral oedema, while consumption of glutamate and alpha-ketoglutarate disturbs neurotransmission and energy metabolism. Lactulose and rifaximin lower gut ammonia production.
Option by option
A. Conversion of ammonia to urea within astrocytes
Astrocytes lack urea cycle enzymes, so urea cannot be made in the brain.
B. Astrocytic glutamine accumulation from ammonia and glutamate, causing osmotic swelling (correct)
Correct. Glutamine is the osmotically active product of astrocytic ammonia detoxification.
C. Accumulation of alpha-ketoglutarate in neurons
Alpha-ketoglutarate is depleted rather than accumulated because it is drawn off to make glutamate.
D. Overproduction of GABA from excess glutamine in the synapse
GABA production is not the main driver of swelling, and the swelling arises from glutamine itself.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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