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It has been widely reported that there is a progressive loss of neurons in the nigrostriatal dopaminergic tract with age. In the human striatum, dopamine content and number of neurons are known to decline rapidly beyond the age of 45 years. I would like to expand on those molecular changes caused by reactions between neurotransmitters and oxygen. I will try to establish a conclusion in which oxygen will appear as the culpable element and main inducer of fundamental changes in the secretions and activity of neurons.
L-dopa is an amino acid that penetrates the blood brain barrier. Inside neurons L-dopa it is metabolized to dopamine, an amine with a different molecular configuration to L-dopa. The enzyme dopa-decarboxylase, take away the carboxylic acid group of L-dopa, and the result is the amine dopamine. (Fig 4) The carboxylic group, COOH, is liberated in this reaction.
Dopamine can be enzymatically or spontaneously oxidized. Spontaneous auto-oxidations of dopamine cause detrimental effects to the brain dopaminergic system. This is clearly observed in normal persons after the age of 45, and in a severe form, in Parkinson's Disease, or other neurological age-related diseases.
I wish to present evidence in support of my hypothesis on ageing which states that atmospheric oxygen is the main environmental factor modulating the process of ageing.
Excess oxygen exerts its effects by damaging neuronal areas directly involved with the neuroendocrine system. The secretion of several hormones is dependent on the availability of neurotransmitters like dopamine, which in turn, directly responsible for the secretions of growth hormone releasing hormone (GHRH) from the hypothalamus.
I will present structural details of the chemical reactions between oxygen and the neurotransmitter dopamine. I hope to integrate my ideas with published research to biochemically confirm the fact that high oxygen pressure in brain tissues, is the main inducer of age-correlated damage in the dopaminergic system.
The first experimental result confirming that dopamine could be auto-oxidized to form 6-hidorxydopamine, was published in 1959. The reaction is non enzymatic, occurs spontaneously, and adds an atom of oxygen to position 6 of the dopamine carbon ring.
A different reaction of dopamine with oxygen is an enzymatic catalyzed reaction. In this second type of reaction, dopamine reacts with oxygen to produce norepinephrine (noradrenaline). The enzyme catalyzing the reaction is dopamine beta-oxidase, which adds oxygen to the CH2 group of dopamine. (Recall that the spontaneous reaction to form 6-hydroxydopamine adds oxygen to position 6 of the carbon ring of dopamine.) (Colour Plate 14, page 90)
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