Fetal fuels. IV. Regulation of branched-chain amino and keto acid metabolism in fetal brain.
|
| Abstract |
The regulation of branched-chain amino and keto acid metabolism was examined in fetal rat brains at 20 days gestation. When fetal brain slices were incubated with [1-14C]leucine, graded concentrations of beta-hydroxybutyrate or acetoacetate resulted in a progressive rise in labeled alpha-ketoisocaproic acid accompanied by a fall in 14CO2, whereas the sum of these products remained unchanged. These reciprocal relationships were maintained when leucine concentrations were varied from 0.4 to 4 mM. Increasing concentrations of glucose or pyruvate enhanced the formation of both 14CO2 and alpha-ketoisocaproic acid from [1-14C]leucine, but resulted in a progressive decrease in the conversion of alpha-ketoisocaproic acid to 14CO2. That glucose and ketone bodies probably acted via separate mechanisms was suggested by a further inhibition of alpha-ketoisocaproic acid decarboxylation whenever beta-hydroxybutyrate was added. When mothers were starved from days 18-20, a threefold rise in circulating branched-chain keto acids was reflected concordantly in the fetus and was attended by a significant enhancement of leucine transaminase activity in fetal brain. Because levels of circulating ketone bodies reported during maternal starvation were maximally effective in diminishing the conversion of alpha-ketoisocaproic acid to 14CO4, it is suggested that the inhibitory effects of beta-hydroxybutyrate on the critical dehydrogenase step in branched-chain keto acid metabolism in fetal brain could restrain oxidation of maternally derived alpha-ketoisocaproic acid, thereby permitting salvage for reversible transamination to leucine.
|
|---|---|
| Authors | G E Shambaugh 3rd, R A Koehler |
| Journal | The American journal of physiology (Am J Physiol) Vol. 241 Issue 3 Pg. E200-7 (Sep 1981) ISSN: 0002-9513 [Print] United States |
| PMID | 7282922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!