Transport of alpha-keto analogues of amino acids across blood-brain barrier in rats.
The transport of 14C-labeled alpha-keto acids across the blood-brain barrier (BBB) was studied in rats anesthetized with sodium pentobarbital using a modification of a single-injection dual-isotope technique. alpha-Keto acids were found to cross the BBB via a saturable carrier-mediated transport system that may be specific based on lack of inhibition by glucose, isoleucine, and ketone bodies on the uptake of tracer levels of 14C-labeled alpha-keto acids. alpha-Ketobutyrate and alpha-keto-gamma-methiolbutyrate, both straight chain keto acids, and alpha-ketoisocaproate, a branched-chain keto acid, appeared to cross the barrier by a common carrier based on cross-inhibition studies. Aromatic keto acids had no effect on the uptake of tracer levels of these 14C-keto acids. The Km of transport of alpha-ketobutyrate, alpha-ketoisocaproate, and alpha-keto-gamma-methiolbutyrate, was 0.11, 0.60, and 0.33 mM, respectively. The corresponding Vmax was 15.7, 73.3, and 30.2 nmol . g-1 . min-1. Phenylpyruvate was found not to cross the BBB. Inhibition of brain uptake of alpha-keto acids by propionate and pyruvate, and not by DL-beta-hydroxybutyrate suggests that alpha-keto acids and monocarboxylic acids are transported either via a common system independent of ketone bodies or share an affinity with a monocarboxylic acid and an alpha-keto acid transport system.
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier; D002250:Carbon Radioisotopes; D007651:Keto Acids / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002250:Carbon Radioisotopes; D007651:Keto Acids