THE AMINO ACID CONTENT OF HUMAN CEREBROSPINAL FLUID IN NORMAL INDIVIDUALS AND IN MENTAL DEFECTIVES*
Authors: Thomas L. Perry, Richard T. Jones
Journal: Journal of Clinical Investigation (1961)

This investigation of the concentrations of hydrolysis of glutamine to ammonia, and subse- amino acids in human cerebrospinal fluid (`CSF) quent colorimetric determination of ammonia was stimulated by curiosity as to the mechanism (7-9).The most recent studies by XInauff, Zick- of mental defect in various genetically determined graf and Mialkowsky (10, 11) have used com- diseases.Studies of serum amino acids 'and of bined -high voltage paper electrophoresis and the pattern of their urinary excretion have in re-paper chromatography for the qualitative identifica- cent years made significant contributions to an tion of amino acids in CSF.-They found 25 nin- understanding of the biochemical etiology of some hydrin-positive substances, of which they were types of mental deficiency.But it seems likely able to identify 21.There has been a lack of that in some conditions abnormalities in the bio-agreement among investigators, in particular con- chemistry of the central nervous system may be cerning the normal occurrence of y-aminobutyric overlooked if studies are confined to those metabo-acid, cystine, proline, and methionine in CSF.lites excreted in the urine or to those circulating Most studies to date have failed to show dif- in the blood.Because the CSF is not merely an ferences between the amino acid pattern of nor- ultrafiltrate formed by way of the choroid plexuses, mal CSF and of that found in neurological dis- but is the product of an exchange between -the ease.Exceptions are the reports of high CSF blood and the central nervous system, examination levels of argininosuccinic acid in argininqsuccinicof this fluid may sometimes yield important clues aciduria (1), of phenylalanine in phenylketonuria to deranged cerebral metabolism.In the recently (12), of glutamine in hepatic coma (7-9), and of discovered disorder argininosuccinicaciduria (1), aspartic acid in hereditary cerebellar ataxia (13).for instance, the concentration of argininosuccinicThe development of the automatic amino acid acid has been found to be greater in CSF than in analyzer ( 14) has made possible more accurate plasma, thus suggesting that the brain rather and rapid measurement of a number of ninhydrin- than some other organ is the site of the metabolic 'positive substances in physiological fluids.In the error.present study this instrument was used to deter- Recent reports concerning-theamino acids found mine the concentrations of amino acids in normal in normal human CSF are confusing.Different pooled CSF.A preliminary investigation was investigators have found as few as seven to as also made of possible differences in amino acids many as 2-1 amino acids present.Using paper in the CSF of patients suffering from a variety of chromatographic techniques, quantitative estima-genetically determined diseases involving mental tion of the amino acids in CSF has been attempted defect.by Torre, Scarzella and Zanalda (2), Porcellati and Kemali (3), Walker, Telles and Pastore (4), MATERIALS AND METHODS and by Logothetis (5).Huisman (6) made use Pooled CSF from adults was used in the study of of quantitative column chromatography for the amino acid concentrations in normal individuals.Ideally determination of amino acids in CSF.Glutamine it would have been desirable to study individual CSF concentrations in CSF have been estimated by specimens, and to obtain the fluid from children, since most of the mental defectives studied were children; but * Supported by a grant from the Ford Foundation.there seemed no justification for collecting CSF from t This investigation was carried out during tenure of normal children, nor for collecting sufficient fluid from a Postdoctoral Fellowship from the United States Public individual normal adults to make possible individual Health Service.aminoiacid determinations.Accordingly, three pools nf 1363