Formation and excretion of NH3----NH4+. New aspects of an old problem.
The proximal tubule cell is the major site of renal ammoniagenesis. Glutamine is the major substrate. Deamidation by mitochondrial glutaminase yields glutamate- and NH4+ (not NH3, as traditionally taught). A second NH4+ ion is obtained by deamination of glutamate- to 2-oxo-glutarate2-. NH4+ preferentially enters the tubule lumen primarily, but probably not exclusively, by non-ionic diffusion of NH3. For each NH3 formed in the cell one H+ ion is left behind. H+ and NH3 are secreted on separate routes, but recombine in the lumen to NH4+ and reach the final urine in this form. This process per se does not net-remove H+ from the organism. For this purpose, the anionic products of ammoniagenesis (2-oxo-glutarate2- and others) have to be converted into neutral compounds (CO2, glucose). This metabolism again takes place usually in the tubule cell. For each negative charge one HCO3- is formed which enters the peritubular blood. Luminal gamma-glutamyl transferase-mediated ammoniagenesis contributes to NH4+ accumulation in the proximal tubule to a small extent. The endproximal NH4+ delivery exceeds the filtered load by a factor of 9. Only 1/3 of it reaches the distal convoluted tubule mainly because NH+4 as such is reabsorbed from the thick ascending limb of Henle's loop by secondary active transport or electrodiffusion. Both processes are energized by the active Na+ transport in this segment. Thereby NH3----NH4+ is accumulated in the medullary interstitium, which establishes the chemical gradient for non-ionic diffusion of NH3 into the lumen of the collecting ducts. This is favoured by the acidic disequilibrium pH in the lumen of this segment.(ABSTRACT TRUNCATED AT 250 WORDS)
D000136:Acid-Base Equilibrium; D000641:Ammonia / Q000652:urine*; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D005972:Glutaminase / Q000502:physiology; D005973:Glutamine / Q000502:physiology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000502:physiology; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D008099:Liver / Q000502:physiology; D008138:Loop of Henle / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D005723:gamma-Glutamyltransferase / Q000502:physiology
D007473:Ion Channels; D005973:Glutamine; D000641:Ammonia; D005723:gamma-Glutamyltransferase; D005972:Glutaminase