Amino acids and related compounds were measured in various regions of brain obtained at autopsy from eight neurologically normal persons, one patient with Parkinson's disease, and eight patients with Huntington's chorea. γ-Aminobutyric acid (GABA) and homocarnosine, a related dipeptide, were reduced in the substantia nlgra, putamen-globus-pallidus, and caudate nucleus of the choreic patients, as compared to the normal subjects and the patient with Parkinsonism. Glycerophosphoethanolamine concentration was elevated in these three regions of choreic brain. Deficiency of γ-aminobutyric acid, a possible inhibitory synaptic transmitter in brain, might produce the symptoms characteristic of Huntington's chorea. Such a deficiency could result from reduced activity of the enzyme glutamic acid decarboxylase, or might reflect a decrease in the number of neurons that normally utilize γ-aminobutyric acid as a transmitter.

Huntington's chorea. Deficiency of gamma-aminobutyric acid in brain.

Parkinson's disease: a disorder due to nigral glutathione deficiency?

Idiopathic Parkinson's disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients

Sequence identification and characterization of human carnosinase and a closely related non-specific dipeptidase.

— Contents (μmol/g wet wt.) of 35 free amino acids and related compounds were measured in 12 different regions of each of five human brains. Specimens were obtained at autopsy from patients who died suddenly without previous brain disease. These data may serve for later comparison with contents of amino compounds in similar regions of the brains of patients dying with various neurological or psychiatric disorders.



There were marked and consistent differences in the regional distribution of the following eight compounds: γ-aminobutyric acid, homocarnosine, glutamic acid, aspartic acid, taurine, cystathionine, glycerophosphoethanolamine, and phosphoethanolamine. These differences suggest that some of these compounds may have special physiological roles, including the possible mediation of synaptic transmission.



Human brain contains two previously unreported compounds, the mixed disulphide of cysteine and glutathione and α-(γ-aminobutyryl)-lysine. The latter dipeptide occurs in much higher concentrations in human brain than in the brains of lower mammals.

Regional distribution of amino acids in human brain obtained at autopsy.

A versatile lithium buffer elution system for single column automatic amino acid chromatography

Plasma-aminoacid levels in huntington's chorea

—Homocarnosine, rather than carnosine, is the major imidazole dipeptide present in human CSF. This compound can be readily detected in the CSF of normal infants and young children, while it is either not detectable or is present only in very small concentrations in the CSF of normal adult subjects. Slightly greater amounts of homocarnosine can be found in the CSF of some adults with neurological disorders.

Dorothy Stedman

Papers

A versatile lithium buffer elution system for single column automatic amino acid chromatography

Plasma-aminoacid levels in huntington's chorea

Homocarnosine in human cerebrospinal fluid: an age-dependent phenomenon.