Hemoglobin: A Nitric-Oxide Dioxygenase

Table 1

Some important biological targets and actions of NO.

Target Reaction	Sensitivity (Est.)	Consequence	Reference
Aconitase (mitochondrial)	>50 nM	Citric acid cycle inhibition	[141–147]
IRE-BP (cytosolic aconitase)	Nanomolar	Iron homeostasis	[143, 146, 148–150]
6-phosphogluconate dehydratase	>50 nM	Entner-Doudoroff pathway inhibition	[151]
Dihydroxy acid dehydratase	Nanomolar	Branched chain amino acid deficiency	[152–154]
Iron-sulfur enzymes; (e.g., dehydratases above)	Nanomolar	Formation of toxic iron-dinitrosyl complexes	[146, 155–158]
Cytochrome oxidase; (and other terminal oxidases)	Nanomolar	Respiratory inhibition	[141, 142, 159–166]
Catalase	Nanomolar	H2O2 damage	[167–169]
Prolyl hydroxylase family	Nanomolar	Hif-1α stabilization and hypoxic response, collagen cross-linking	[170, 171]
Cytochrome P450 family	Nanomolar	Metabolism of hormones, lipid second messengers, and so forth, Heme release and damage.	[172–174]
Ribonucleotide reductase (diiron)	Nanomolar-micromolar	Inhibition of DNA synthesis	[175–178]
Heme oxygenase family	Nanomolar	Inhibition of toxic heme breakdown	[179, 180]
Photosystem II	?	Inhibition of photosynthesis	[181]
Nitrogenase	Nanomolar-micromolar	Inhibition of N2 fixation	[182–187]
Hydrogenase	Nanomolar	Inhibition of N2 fixation	[188]
O2	Micromolar	NO2 damage	[189]
O2^−	Nanomolar	Peroxynitrite damage	[189, 190]
Guanylate cyclase	0.1–10 nanomolar	cGMP kinase activation and smooth muscle relaxation	[191, 192]
Transcription regulators (NorR, NsrR, DevS, etc.)	Nanomolar	NO defense gene expression	[80, 193–196]
ACO (1-aminoacyl cyclopropane-1-carboxylic acid oxidase)	Nanomolar	Ethylene production and signaling in plants	[197]