Hyperammonemia induces polymerization of brain tubulin.

Rats were made hyperammonemic by feeding them a diet containing ammonium acetate. The tubulin content in their brain increased greater than or equal to 30% after 20 days on the diet. All the increase was found in polymerized tubulin; no increase in free tubulin was noted. When rats on the ammonium diet were then fed the standard diet, the tubulin increased slightly on the first day but decreased markedly on the second day, reaching control values on the third day. It should be noted that brain tubulin synthesis, was not reduced on the first day of feeding the standard diet but was markedly inhibited (to approximately 40% of control) on the second day, returning to control values on the third day. On the first day of refeeding there is a remarkable disassembly of microtubules with a large, proportional increase (approximately 50%) of free tubulin. Both free and polymerized tubulin levels returned to control values on the third day. These results indicate that in hyperammonemia changes in the degree of polymerization of tubulin preceded those in tubulin synthesis.