Blood-brain barrier transport of the alpha-keto acid analogs of amino acids.
A number of alpha-keto acid analogs of amino acids have been found to penetrate the blood-brain barrier (BBB). Pyruvate, alpha-ketobutyrate, alpha-ketoisocaproate, and alpha-keto-gamma-methiolbutyrate all cross the BBB by a carrier-mediated process and by simple diffusion. Under normal physiological conditions, diffusion accounts for roughly 15% or less of total transport. Aromatic alpha-keto acids, phenylpyruvate, and p-hydroxyphenylpyruvate do not penetrate the BBB, nor do they inhibit the transport of other alpha-keto acids. Evidence based primarily on inhibition studies indicates that the carrier-mediated transport of alpha-keto acids occurs via the same carrier demonstrated previously for propionate, acetoacetate, and beta-hydroxybutyrate transport, commonly referred to as the monocarboxylate carrier. As a group, the alpha-keto acid analogs of the amino acids have the highest affinity for the carrier, followed by propionate and beta-hydroxybutyrate. Starvation for 4 days induces transport of alpha-keto acids, but transport is suppressed in rats fed commercial laboratory rations and subjected to portacaval shunts. The mitochondrial pyruvate translocator inhibitor alpha-cyanocinnamate has no effect on the BBB transport of alpha-keto acids.
D020155:3-Hydroxybutyric Acid; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002264:Carboxylic Acids / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology; D004058:Diffusion; D006885:Hydroxybutyrates / Q000378:metabolism; D007651:Keto Acids / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism; D007700:Kinetics; D008715:Methionine / Q000031:analogs & derivatives / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters; D011422:Propionates / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D013217:Starvation / Q000378:metabolism
D000596:Amino Acids; D002264:Carboxylic Acids; D002352:Carrier Proteins; D003373:Coumaric Acids; D006885:Hydroxybutyrates; D007651:Keto Acids; D007656:Ketoglutaric Acids; D027501:Monocarboxylic Acid Transporters; D011422:Propionates; D011773:Pyruvates; C007175:alpha-cyano-4-hydroxycinnamate; C014632:2-keto-4-methylthiobutyric acid; C013082:alpha-ketoisocaproic acid; D019289:Pyruvic Acid; D008715:Methionine; C029658:propionic acid; D020155:3-Hydroxybutyric Acid