3 Histidine
Histidine is metabolized through three different pathways, of which decarboxylation to histamine yields the active neurotransmitter histamine in the tuberomamillary neurons of the brain. l -Histidine is transported into the brain through the blood–brain b
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Histidine
P. Panula
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
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Histidine Transport and Uptake in Brain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
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Metabolism of Histidine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
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Histidine as Histamine Precursor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50
5 5.1 5.2 5.3
Histidinemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Mechanism and Consequences of Histidinemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 Brain Disorders Related to Histidinemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 Portocaval Anastomosis and Histidinemia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
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Summary and Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
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Springer-Verlag Berlin Heidelberg 2007
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Histidine
Abstract: Histidine is metabolized through three different pathways, of which decarboxylation to histamine yields the active neurotransmitter histamine in the tuberomamillary neurons of the brain. L‐Histidine is transported into the brain through the blood–brain barrier (BBB) by a system that recognizes several amino acids. Lack of functional histidase activity because of an autosomal recessive disorder leads to elevated histidine levels in the blood, which is occasionally associated with neurological symptoms, although the disorder is generally considered benign. Experimental histidinemia is associated with increased levels of histamine, which accumulates in brain histaminergic neurons and their axons. Histamine is the major biologically active product derived from L‐histidine in histidinemia, and it can potentially have functional significance because of the actions of histamine on the four known G protein‐coupled histamine receptors, of which three are abundantly expressed in the brain. List of Abbreviations: AP2/KER1, transcription factor AP2/KER1; BBB, blood-brain barrier; BCH, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid; BMEC, Brain microvascular endothelial cells; C/EBP, transcription factor C/EBP; DQ, developmental quotient; g17, human amino acid transporter g17; HDC, L-Histidine decarboxylase; HE, hepatic encephalopathy; HNF5, liver-specific DNA-binding protein HNF5; IQ, intelligence quotient; LAT1,
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