Biomaterial Database

Are neuropsychiatric manifestations of folate, cobalamin and pyridoxine deficiency mediated through imbalances in excitatory sulfur amino acids? 1994

C R Santhosh-Kumar, and K L Hassell, and J C Deutsch, and J F Kolhouse

Department of Medicine, University of Colorado Health Sciences Center, Denver.

Folate, cobalamin and pyridoxine deficiency are associated with psychiatric or neurological symptomatology. Disturbances in sulfur amino acid metabolism leading to accumulation of homocysteine occurs in all three conditions as the metabolism of homocysteine depends on enzymes requiring these vitamins as cofactors. Oxidation products of homocysteine (homocysteine sulfinic acid and homocysteic acid) and cysteine (cysteine sulfinic acid and cysteic acid) are excitatory sulfur amino acids and may act as excitatory neurotransmitters, whereas taurine and hypotaurine (decarboxylation products of cysteic acid and cysteine sulfinic acid) may act as inhibitory transmitters. Homocysteic acid and cysteine sulfinic acid have been considered as endogenous ligands for the N-methyl-D-aspartate (NMDA) type of glutamate receptors. The profile of these sulfur amino acid neurotransmitters could be altered in a similar fashion in states of decreased availability of folate, cobalamin or pyridoxine. It is proposed that the mechanism of neuropsychiatric manifestations in all three conditions result from a combination of two insults to homocysteine catabolism in the brain.

UI	MeSH Term	Description	Entries
D001921	Brain	The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.	Encephalon
D001927	Brain Diseases	Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.	Intracranial Central Nervous System Disorders,Brain Disorders,CNS Disorders, Intracranial,Central Nervous System Disorders, Intracranial,Central Nervous System Intracranial Disorders,Encephalon Diseases,Encephalopathy,Intracranial CNS Disorders,Brain Disease,Brain Disorder,CNS Disorder, Intracranial,Encephalon Disease,Encephalopathies,Intracranial CNS Disorder
D005494	Folic Acid Deficiency	A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed)	Deficiency, Folic Acid,Acid Deficiencies, Folic,Acid Deficiency, Folic,Deficiencies, Folic Acid,Folic Acid Deficiencies
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000603	Amino Acids, Sulfur		Sulfur Amino Acid,Sulfur Amino Acids,Acid, Sulfur Amino,Acids, Sulfur Amino,Amino Acid, Sulfur
D001523	Mental Disorders	Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function.	Mental Illness,Psychiatric Diseases,Psychiatric Disorders,Psychiatric Illness,Behavior Disorders,Diagnosis, Psychiatric,Mental Disorders, Severe,Psychiatric Diagnosis,Illness, Mental,Mental Disorder,Mental Disorder, Severe,Mental Illnesses,Psychiatric Disease,Psychiatric Disorder,Psychiatric Illnesses,Severe Mental Disorder,Severe Mental Disorders
D014806	Vitamin B 12 Deficiency	A nutritional condition produced by a deficiency of VITAMIN B 12 in the diet, characterized by megaloblastic anemia. Since vitamin B 12 is not present in plants, humans have obtained their supply from animal products, from multivitamin supplements in the form of pills, and as additives to food preparations. A wide variety of neuropsychiatric abnormalities is also seen in vitamin B 12 deficiency and appears to be due to an undefined defect involving myelin synthesis. (From Cecil Textbook of Medicine, 19th ed, p848)	Deficiency, Vitamin B 12,Deficiency, Vitamin B12,Vitamin B12 Deficiency,Deficiencies, Vitamin B12,Vitamin B12 Deficiencies
D016194	Receptors, N-Methyl-D-Aspartate	A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity.	N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D018846	Excitatory Amino Acids	Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear.	Amino Acids, Excitatory,Excitatory Amino Acid,Acid, Excitatory Amino,Acids, Excitatory Amino,Amino Acid, Excitatory
D026681	Vitamin B 6 Deficiency	A nutritional condition produced by a deficiency of VITAMIN B 6 in the diet, characterized by dermatitis, glossitis, cheilosis, and stomatitis. Marked deficiency causes irritability, weakness, depression, dizziness, peripheral neuropathy, and seizures. In infants and children typical manifestations are diarrhea, anemia, and seizures. Deficiency can be caused by certain medications, such as isoniazid.	Pyridoxine Deficiency,Deficiency, Pyridoxine,Deficiency, Vitamin B 6,Deficiency, Vitamin B6,Vitamin B6 Deficiency,Vitamin Deficiency, B6,B6 Deficiencies, Vitamin,B6 Deficiency, Vitamin,B6 Vitamin Deficiencies,B6 Vitamin Deficiency,Deficiencies, B6 Vitamin,Deficiencies, Vitamin B6,Deficiency, B6 Vitamin,Vitamin B6 Deficiencies,Vitamin Deficiencies, B6