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326 Tissues and organs
Functions in the acid–base balance B. Ammonia excretion
Approximately 60 mmol of protons are ex-
Along with the lungs, the kidneys are partic-
ularly involved in keeping the pH value of the creted with the urine every day. Buffering
systems in the urine catch a large proportion
extracellular fluid constant (see p. 288). The +
contribution made by the kidneys particularly of the H ions, so that the urine only becomes
weakly acidic (down to about pH 4.8).
–
involves resorbing HCO 3 and actively excret-
ing protons. An important buffer in the urine is the
hydrogen phosphate/dihydrogen phosphate
2–
–
system (HPO 4 /H 2 PO 4 ). In addition, ammo-
A. Proton excretion nia also makes a vital contribution to buffer-
ing the secreted protons.
The renal tubule cells are capable of secreting Since plasma concentrations of free am-
+
protons (H ) from the blood into the urine monia are low, the kidneys release NH 3 from
against a concentration gradient, despite the glutamine and other amino acids. At
+
fact that the H concentrationinthe urine is
up to a thousand times higher than in the 0.5–0.7 mM, glutamine is the most important
amino acid in the plasma and is the preferred
blood. To achieve this, carbon dioxide (CO 2 )
is taken up from the blood and—together with form for ammonia transport in the blood. The
water (H 2 O) and with the help of carbonate kidneys take up glutamine, and with the help
of glutaminase [4], initially release NH 3 from
dehydratase (carbonic anhydrase, [1])—con-
verted into hydrogen carbonate (“bicarbo- the amide bond hydrolytically. From the glu-
tamate formed, a second molecule of NH 3 can
+
–
nate,” HCO 3 )and one H . Formally, this yields
carbonic acid H 2 CO 3 as an intermediate, but it be obtained by oxidative deamination with
the help of glutamate dehydrogenase [5] (see
is not released during the reaction. p. 178). The resulting 2-oxoglutarate is fur-
The hydrogen carbonate formed in car-
bonic anhydrase returns to the plasma, where ther metabolized in the tricarboxylic acid
cycle. Several other amino acids—alanine in
it contributes to the blood’s base reserve. The
proton is exported into the urine by secondary particular, as well as serine, glycine, and
aspartate—can also serve as suppliers of am-
+
active transport in antiport for Na (bottom monia.
right). The driving force for proton excretion,
as in other secondary active processes, is the Ammonia can diffuse freely into the urine
+
Na gradient established by the ATPase in- through the tubule membrane, while the am-
+
+
+
+
volved in the Na /K exchange (“Na /K AT- monium ions that are formed in the urine are
charged and can no longer return to the cell.
Pase”, see p. 220). This integral membrane Acidic urine therefore promotes ammonia ex-
proteinonthe basalside (towards the blood)
+
of tubule cells keeps the Na concentration in cretion, which is normally 30–50 mmol per
day. In metabolic acidosis (e. g., during fasting
the tubule cell low, thereby maintaining Na +
inflow. In addition to this secondary active H + or in diabetes mellitus), after a certain time
increased induction of glutaminase occurs in
+
transport mechanism, there is a V-type H - the kidneys, resulting in increased NH 3 excre-
transporting ATPase in the distal tubule and +
collecting duct (see p. 220). tion. This in turn promotes H release and
thus counteracts the acidosis. By contrast,
An important function of the secreted H +
-
ions is to promote HCO 3 resorption (top when the plasma pH value shifts towards
alkaline values (alkalosis), renal excretion of
right). Hydrogen carbonate, the most impor- ammonia is reduced.
tant buffering base in the blood, passes into
the primary urine quantitatively, like all ions.
–
In the primary urine, HCO 3 reacts with H +
ions to form water and CO 2 ,which returns
by free diffusion to the tubule cells and from
there into the blood. In this way, the kidneys
–
also influence the CO 2 /HCO 3 buffering bal-
ance in the plasma.
Koolman, Color Atlas of Biochemistry, 2nd edition © 2005 Thieme
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