(1974). Recommended Methods for the Determination of Four Enzymes in Blood. Scandinavian Journal of Clinical and Laboratory Investigation: Vol. 33, No. 4, pp. 291-306.

Recommended Methods for the Determination of Four Enzymes in Blood

The Dopamine Hypothesis of Schizophrenia: A Review*

Molecular Neurobiology of the Mammalian Brain

Aldehydes are highly reactive molecules formed during the biotransformation of numerous endogenous and exogenous compounds, including biogenic amines. 3,4-Dihydroxyphenylacetaldehyde is the aldehyde metabolite of dopamine, and 3,4-dihydroxyphenylglycolaldehyde is the aldehyde metabolite of both norepinephrine and epinephrine. There is an increasing body of evidence suggesting that these compounds are neurotoxic, and it has been recently hypothesized that neurodegenerative disorders may be associated with increased levels of these biogenic aldehydes. Aldehyde dehydrogenases are a group of NAD(P)+-dependent enzymes that catalyze the oxidation of aldehydes, such as those derived from catecholamines, to their corresponding carboxylic acids. To date, 19 aldehyde dehydrogenase genes have been identified in the human genome. Mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjogren-Larsson syndrome, type II hyperprolinemia, γ-hydroxybutyric aciduria, and pyridoxine-dependent seizures, most of which are characterized by neurological abnormalities. Several pharmaceutical agents and environmental toxins are also known to disrupt or inhibit aldehyde dehydrogenase function. It is, therefore, possible to speculate that reduced detoxification of 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde from impaired or deficient aldehyde dehydrogenase function may be a contributing factor in the suggested neurotoxicity of these compounds. This article presents a comprehensive review of what is currently known of both the neurotoxicity and respective metabolism pathways of 3,4-dihydroxyphenylacetaldehyde and 3,4-dihydroxyphenylglycolaldehyde with an emphasis on the role that aldehyde dehydrogenase enzymes play in the detoxification of these two aldehydes.

Neurotoxicity and Metabolism of the Catecholamine-Derived 3,4-Dihydroxyphenylacetaldehyde and 3,4-Dihydroxyphenylglycolaldehyde: The Role of Aldehyde Dehydrogenase

Myelin basic protein - diverse conformational states of an intrinsically unstructured protein and its roles in myelin assembly and multiple sclerosis

Incorporation of radioactivity from labeled serotonin and tryptamine into acid-insoluble material from subcellular fractions of brain. I. The nature of the substrate.

SEROTONIN (5HT) and tryptamine are metabolized primarily by monoamine oxidase (MAO)1 with the formation of the corresponding aldehyde derivatives 5-hydroxyindole-3-acetaldehyde (5HIAAld) and indoleacetaldehyde (IAAld). These aldehydes are unstable and reactive and are promptly oxidized to corresponding acids2, are firmly bound to acid-insoluble fractions of brain homogenates2–3 or follow other metabolic routes2,4,5, but they are not significantly reconverted to the corresponding amines3. Little attention has been paid to the possible pharmacological activity of these aldehydes because they are inactive in smooth muscle preparations6. We now wish, however, to present evidence that indoleacetaldehydes are biologically active and that to some extent their effects mimic the action of serotonin in visual evoked responses7 and sleep induction9, two functions known to be affected selectively by serotonin probably because the corresponding pathways are normally modulated by the endogenous amine. Our 5HIAAld was prepared enzymatically from 5HT6 and its concentration determined by the 2,4-dinitrophenylhydrazine method9. Its purity was determined by a combination of electrophoretic separation and subsequent autoradiography3; serotonin was not detectable.

Indoleacetaldehydes: Serotonin-like Effects on the Central Nervous System

Spontaneous Reactions of 1,3-Substituted 1,4-Dihydropyridines with Acids in Water at Neutrality. I. Kinetic Analysis and Mechanism of the Reactions of Dihydronicotinamide-Adenine Dinucleotide with Orthophosphates*

Non-enzymic reactions of indoles with pyridine coenzymes and related structures.

WE previously reported1 changes of the absorption spectrum of nicotinamide adenine dinucleotide (coenzyme I, abbreviated NAD+) in solutions containing orthophosphate. In an extension of those investigations2, it has been observed that dihydronicotinamide-adenine dinucleotide (reduced coenzyme I, abbreviated NADH) also reacts with orthophosphate, but in an entirely different manner. Similar changes were observed with dihydronicotinamide adenine dinucleotide phosphate (reduced coenzyme II, abbreviated NADPH) and certain other NADH-analogues. This is a preliminary report of our findings3.

Frieda Ungar

Papers

Incorporation of radioactivity from labeled serotonin and tryptamine into acid-insoluble material from subcellular fractions of brain. I. The nature of the substrate.

Indoleacetaldehydes: Serotonin-like Effects on the Central Nervous System

Spontaneous Reactions of 1,3-Substituted 1,4-Dihydropyridines with Acids in Water at Neutrality. I. Kinetic Analysis and Mechanism of the Reactions of Dihydronicotinamide-Adenine Dinucleotide with Orthophosphates*

Non-enzymic reactions of indoles with pyridine coenzymes and related structures.

Non-enzymatic interactions of reduced coenzyme i with inorganic phosphate and certain other anions.