Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ventilatory acclimatization to hypoxia (VAH) is a time-dependent increase in ventilation and ventilatory O2-sensitivity that involves plasticity in carotid body chemoreceptors and CNS respiratory centers. Hypoxia inducible factor-1alpha (HIF-1alpha) controls the expression of several genes that increase physiological O2 supply. Studies using transgenic mice show HIF-1alpha expression in the carotid bodies and CNS with chronic sustained and intermittent hypoxia is important for VAH. Other O2-sensitive transcription factors such as HIF-2alpha may be important for VAH by reducing metabolic O2 demands also. Specific gene targets of HIF-1alpha shown to be involved in VAH include erythropoietin, endothelin-1, neuronal nitric oxide synthase and tyrosine hydroxylase. Other HIF-1alpha targets that may be involved in VAH include vascular endothelial growth factor, heme oxygenase 1 and cytoglobin. Interactions between these multiple pathways and feedback control of HIF-1alpha expression from some of the targets support a complex and powerful role for HIF-1alpha in neural plasticity of physiological control circuits with chronic hypoxia.
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PMID:HIF-1 and ventilatory acclimatization to chronic hypoxia. 1870 72

This work deals with dioxygen (O2 ) binding sites and pathways through inducible human heme oxygenase (HO-1). The experimentally known distal binding site 1, and sites 2-3 above it, could be reproduced by means of non-deterministic random-acceleration molecular-dynamics (RAMD) simulations. In addition, RAMD revealed the proximal binding site 5, a deeply-seated binding site 4, which lies behind heme, as well as a few gates communicating with the external medium. In getting from site 1 to the main gate, which lies on the protein front opposed to site 4, O2 follows chiefly the shortest direct pathway. Less frequently, O2 visits intermediate sites 2, 4, or 5 along longer pathways. A similarity between HO-1, myoglobin, and cytoglobin in using, for diatomic gas delivery, the direct shortest pathway from the heme center to the surrounding medium, is emphasized. Otherwise, comparing other proteins and diatomic gases, each system reveals its peculiarities as to sites, gates, and pathways. Thus, relating these properties to the physiological functions of the proteins remains in general a challenge for future studies.
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PMID:On the pathways of biologically relevant diatomic gases through proteins. Dioxygen and heme oxygenase from the perspective of molecular dynamics. 2357 42