Transaminase Inhibition by Decaborane ∗

Abstract

The use of the boron hydrides, pentaborane and decaborane, in recent years as high energy propellants has stimulated interest in the mechanism(s) by which this class of compounds expresses its toxic effects.

Boron hydrides are known to cause marked derangements in the biochemical and functional relationships of the central nervous system (1). While there is indirect evidence that many of the effects may be due to inhibition of aromatic amino acid decarboxylases (2), direct evidence has been obtained that 5HTP decarboxylase (EC 4.1.1.26) is inhibited by decaborane (B₀₁H₁₄) (3); these are all pyridoxal-requiring enzymes. For this reason, we chose to examine a number of pyridoxal enzymes, as well as several nonpyridoxal-requiring enzymes, to test the hypothesis that the toxic manifestations of boron hydrides are primarily due to their inhibition of pyridoxal enzymes.

We are reporting our initial results showing the effects of decaborane (B₁₀H₁₄) upon glutamic-oxalacetic transaminase (aspartate aminotransferase, EC 2.6:1.1) activity in the brain, liver, kidneys, serum, and heart of the rat.

Methods Ten male Sprague-Dawley rats weighing 280-480 gm were injected intraperitoneally with 10 mg, and 10 with 20 mg, of tlecal, orane per kg of body weight as a solution in corn oil. Kine control animals were injected with like quantities of corn oil All the anirnals had free access to Purina laboratory chow and to water. It was noted, honever, that those animals injected with tlecahorane seemed to abstain from eating. After 16 hours, the rats were anesthetized with methouyllurane, and a sample of blood was aspirated by cardiac puncture into a heparinized syringe. The liver, bitlneys, heart. and brain were quickly removed, frozen in liquid nitruqen, and stored for 1-3 days at −25°C until assayed. At the time of assay, the tissues were homogenized in 9 volumes of 0.25 −11 sucrose (4) with a Ten Broeck glass homoqenizer.