Relationship of brain glutamine and brain neutral amino acid concentrations after portacaval anastomosis in rats

Publisher Website
Google Scholar
Abstract
Evidence from several sources suggest that blood-brain transport of the large neutral amino acids (NAA) is abnormal in animals with a portacaval anastomosis (PCA) and in patients with liver cirrhosis and portal-systemic shunting and encephalopathy, but the underlying mechanisms are unknown. After PCA, the concentration of glutamine (Gln) in brain is markedly increased as a by-product of cerebral ammonia detoxification, and the rate of efflux of Gln from brain is also increased. Studies were undertaken to clarify the relationships among plasma and brain concentrations of NAA after PCA in rats, and the relationship of brain Gln concentration to plasma and brain NAA concentrations was examined. After PCA plasma phenylalanine, tyrosine and histidine were elevated and leucine, isoleucine and valine were lowered. In brain, phenylalanine, tyrosine, histidine and methionine were markedly elevated after PCA and their concentrations in brain far exceeded the concentrations in plasma. Analyses of single, partial and multiple correlations of plasma NAA ratios expressed as plasma competitor function (PCF), brain NAA and brain Gln showed significant correlations between PCF and brain NAA in shunted rats. A better correlation was found between brain NAA and brain Gln. The effects of PCF and brain Gln on brain NAA were separate and additive. Gln was shown to compete with other NAA for blood brain transport by inhibiting brain 14C phenylalanine uptake. This in combination with the relationship demonstrated between brain Gln concentration and brain NAA concentrations suggests that Gln exerts some effect on blood-brain NAA transport. This has therapeutic implications in patients with liver failure and encephalopathy.