The Importance of the Liver as a Regulator of Amino Acid Supply to the Brain
In mammals, tryptophan and phenylalanine are essential components of the diet, dietary tyrosine being supplemented by hydroxylation of phenylalanine in the liver. The concentrations of the amino acids in the blood are regulated by the rates of dietary intake, protein turnover and peripheral metabolism (occurring mostly in the liver; see Figure 1). The aromatic amino acids are of particular interest because of their role as precursors of several neurotransmitters, i. e., dopamine, noradrenaline and serotonin. The aromatic amino acids share, with many other neutral amino acids, a common transport system into the brain and it is clear that the ratio of their concentrations, as well as their absolute concentrations, is important for neurotransmitter synthesis. The synthesis of serotonin has been shown to be regulated by the supply of its precursor, tryptophan. Tryptophan hydroxylase is considered to be the rate-limiting enzyme for serotonin synthesis and is unsaturated with respect to its substrate, tryptophan (1). Increases or decreases in brain tryptophan will therefore increase or decrease the synthesis of serotonin; the normal concentration of brain tryptophan approximates to the Km of tryptophan hydroxylase for tryptophan (1). The control of brain serotonin is of great importance because of the role of this neurotransmitter in the cerebral functions associated with mood, sleep, sensitivity to pain and appetite.
KeywordsAromatic Amino Acid Neutral Amino Acid Tryptophan Hydroxylase Kynurenine Pathway Phenylalanine Hydroxylase
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