Structural specificity in the renal tubular transport of tyrosine.
The structural requirements for aromatic amino acid reabsorption and secretion in the dog were investigated using a series of tyrosine analogs. In clearance experiments, l-tyrosine and l-phenylalanine underwent net reabsorption at rates 5 to 6 times greater than those of the corresponding d-enantiomers and about 1.5 time those of o- and m-dl-tyrosine. 3-(p-hydroxyphenyl)Propionic acid underwent net secretion under conditions of polyuria and high urinary pH and net reabsorption under conditions of oliguria and low pH. In stop-flow experiments, (U/Pl-amino acid)/(U/Pln) ratios, where U/P = concentration in urine and plasma and In = inulin, of proximal tubular samples were 1.5 to 5-fold greater than the control (free-flow) values of 0.1 to 0.3, indicating tubular secretion. Secretion was inhibited, and net reabsorption enhanced, by probenecid, p-aminohippuric acid and 2,4-dinitrophenol. (U/Pd-amino acid)/(U/PIN) ratios of proximal tubular samples were below the control values of 0.6 to 0.8, indicating tubular reabsorption. Probenecid had no effect on the overall pattern but caused a slight decrease in the relative clearance values. The stop-flow pattern of 3-(p-hydroxyphenyl)propionic acid excretion was similar to that of the I-amino acids. It was concluded that the I-amino acids undergo bidirectional transport and that the I-configuration and amino group are required for optimal active reabsorption, whereas ring hydroxylation has little effect on reabsorption transport. No absolute structural requirements for active secretion were elucidated.
D000042:Absorption; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D004285:Dogs; D005260:Female; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D008297:Male; D010649:Phenylalanine / Q000378:metabolism; D010666:Phenylpropionates / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000378:metabolism
D000596:Amino Acids; D010666:Phenylpropionates; D014443:Tyrosine; D010649:Phenylalanine; C008869:phloretic acid