Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(6R)-L-erythro-5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for tyrosine hydroxylase (TH), tryptophan hydroxylase, phenylalanine hydroxylase, and nitric-oxide synthase. These enzymes synthesize neurotransmitters, e.g. catecholamines, serotonin, and nitric oxide (NO). We established mice unable to synthesize BH4 by disruption of the 6-pyruvoyltetrahydropterin synthase gene, the encoded protein of which catalyzes the second step of BH4 biosynthesis. Homozygous mice were born at the almost expected Mendelian ratio, but died within 48 h after birth. In the brain of homozygous mutant neonates, levels of biopterin, catecholamines, and serotonin were extremely low. The number of TH molecules was highly dependent on the intracellular concentration of BH4 at nerve terminals. Alteration of the TH protein level by modulation of the BH4 content is a novel regulatory mechanism. Our data showing that catecholaminergic, serotonergic, and NO systems were differently affected by BH4 starvation suggest the possible involvement of BH4 synthesis in the etiology of monoamine-based neurological and neuropsychiatric disorders.
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PMID:Catecholamines and serotonin are differently regulated by tetrahydrobiopterin. A study from 6-pyruvoyltetrahydropterin synthase knockout mice. 1151 15

Hormone receptors, hormones and signal transduction pathways characteristic of higher vertebrates can be observed also in the unicellular Tetrahymena. Previous work showed that stress conditions (starvation, high temperature, high salt concentration, formaldehyde or alcohol treatment) elevated the intracellular level of four hormones (ACTH, endorphin, serotonin and T(3)). Here, the effect of other stressors (CuSO4 poisoning, tryptophan hydroxylase inhibitor parachlorophenylalanine (PCPA) treatment) on the same and other hormones (epinephrine, insulin, histamine) was studied, using immunocytochemistry and flow cytometric analysis. It was found, that each effect increased the intracellular hormone contents, but some hormones (histamine, T(3)) were less reactive. Insulin--which is a life-saving factor for Tetrahymena--itself provoked elevation of hormone amounts in association with a stressor, further increased the level of hormones. It was concluded that the ancestor of Selye's General Adaptation Syndrome (GAS) can be found already at unicellular level, and this possibly has a life saving function.
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PMID:How applicable is the general adaptation syndrome to the unicellular Tetrahymena? 1910 78

Research into how protein restriction improves organismal health and lengthens lifespan has largely focused on cell-autonomous processes. In certain instances, however, nutrient effects on lifespan are independent of consumption, leading us to test the hypothesis that central, cell non-autonomous processes are important protein restriction regulators. We characterized a transient feeding preference for dietary protein after modest starvation in the fruit fly, Drosophila melanogaster, and identified tryptophan hydroxylase (Trh), serotonin receptor 2a (5HT2a), and the solute carrier 7-family amino acid transporter, JhI-21, as required for this preference through their role in establishing protein value. Disruption of any one of these genes increased lifespan up to 90% independent of food intake suggesting the perceived value of dietary protein is a critical determinant of its effect on lifespan. Evolutionarily conserved neuromodulatory systems that define neural states of nutrient demand and reward are therefore sufficient to control aging and physiology independent of food consumption.
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PMID:Serotonin signaling mediates protein valuation and aging. 2757 62