In a patient with chronic metabolic acidosis, the kidney adapts by increasing excretion of ammonium. Which substrate and cellular location provide the ammonia that carries the largest share of this adaptive response?

• A Glutamate, decarboxylated in alpha-intercalated cells
• B Alanine, transaminated in the cytosol of thick ascending limb cells
• C Urea, hydrolyzed by urease in collecting duct cells
• D Glutamine, metabolized in the mitochondria of proximal tubular cells ✓

Explanation

Adaptive ammoniagenesis uses glutamine taken up by proximal tubular cells and deaminated by mitochondrial glutaminase and glutamate dehydrogenase, yielding two ammonium ions and two new bicarbonate molecules per glutamine. Chronic acidosis upregulates this pathway over days. Alpha-intercalated cells secrete preformed ammonium but do not synthesize it from glutamine, and no urease enzyme exists in human renal tissue.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.