ISSN:
1432-2013
Keywords:
Na+-dependent transport
;
d-Lactate transport
;
Small fatty acids
;
3-Hydroxybutyrate
;
Acetoacetate
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract The 3.5 s efflux ofd-lactate (1 mmol/l) injected in the lumen of the late proximal convolution as well as the zero net flux transtubular concentration difference ofd-lactate, which is a measure of its active transtubular transport rate, were determined. The inhibitory potency of small fatty acids and their analogs added to the perfusate in a concentration of 10 mmol/l on both, the 3.5 s efflux and in most cases also the 45 s transtubular concentration difference ofd-lactate was measured. It was found that 1. small fatty acids from acetate to octanoate inhibit 3.5s efflux ofd-lactate, the largest inhibition being exerted by propionate and butyrate. With increasing chain length the inhibitory potency decreased and disappeared with decanoate. 2. Considering the acetate-, propionate- and butyrate analogs, introduction of an electron attracting group such as Cl, Br, I, CN, SH, N3 on C atom 2 increased the inhibitory potency, compared to the unsubstituted fatty acid. An OH on C2 increased or did not change the inhibition while an OH on C atom 3 reduced or blunted the inhibition. A keto-group, as it is present in glyoxylate prevented inhibition, but pyruvate inhibited to the same extent as lactate, and acetoacetate was even more inhibitory than 3-hydroxybutyrate. Cl substitution on C3 preserved the strong inhibitory potency, while 4-Cl butyrate, was only sparsely inhibitory. A NH 3 + group at any position precludes inhibition. 3. As seen with Cl or OH substituted propionate and butyrate the inhibitory potency increased with decreasingpK a of the compounds. 4. Increasing the chain length by a CH3 as from acetate to propionate, from glycolate to lactate and also from glyoxylate to pyruvate increased the inhibitory potency. 5. When tested against the 3.5 s efflux ofl-lactate, the same inhibitory pattern was seen as withd-lactate. 6. The transport of chloroacetate, glycolate and acetoacetate, which were available in a radio-labeled form of high specific activity, was measured directly in 3.5 s efflux studies. It was Na+-dependent and could be inhibited by 10 mmol/ll-lactate. Glyoxylate, on the other hand, which did not inhibitd-lactate transport, did also not show a Na+-dependent,l-lactate inhibitable efflux from the tubular lumen. The data indicate that a variety of short chain fatty acids and their analogs are transported by the same Na+-dependent transport system in the brush border which transportsl- andd-lactate. The specificity is determined by the molecule size, hydrophobicity of one part of the molecule, the electron attracting abilities of substitutes on C-atom 2 or 3 and the charge distribution on the molecule.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00584813
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