Renal transport of amino acids

Abstract

According to recent experimental data the renal transport of amino acids (AA) is characterized as follows. 1. Kinetics: Several reabsorption systems remove AA from the tubular fluid by active transport with Michaelis-Menten type kinetics. Passive diffusion does play only a relatively small role in reabsorption, but determines the pump leak steady state concentration at the end of the tubule. 2. Stereospecificity: Except for aspartate the naturally occurring L-analogs show a much larger affinity to the transport "carriers" than the D-isomers do. 3. Specificity: Separate transport mechanisms exist for a) the "acidic" AA (Glu and Asp); b) the "dibasic" AA (Arg, Lys, Orn); c) cystine/cystine; d) the "imino" acids (Pro, OH-Pro and other N-substituted AA); e) the beta- and gamma-AA (beta-Ala, GABA, Taurine); f) all other "neutral" AA. For the group (d) and maybe also for (b) and glycine additional low capacity/high affinity systems exist. 4. Localization: Except for glycine and taurine under normal conditions more than 80% of the filtered load are reabsorbed within the first third of the proximal tubule. At an elevated load the rest of the proximal tubule (including pars recta) but not the distal nephron is included into the reabsorptive process. AA are also taken up from the peritubular blood. 5. Energy sources: At least the main part of AA uptake at the brushborder membrane is dependent from a transmembranal Na+-gradient which in turn is established by the ATP driven Na+-pumps at the basolateral side of the cell (Secondary active transport or co-transport of AA). 6. Biochemistry: The biochemical nature of the AA-"carriers" is unknown. The recent hypothesis than a "gamma-glutamyl cycle" plays a major role in this context has been disproved to great extent. 7. Peptides: Oligopeptides (Angiotensin, Gluthathion) filtered at the glomerulum are hydrolyzed by brushborder peptidases within the tubule lumen. The splitting products, the free constituent amino acids, are reabsorbed subsequently by their respective transport systems.