Citrulline (source code)

= Citrulline

<Citrulline> is an <amino acid> whose side chain has the structure $\mathrm{-(CH_2)_3-NH-C(=O)-NH_2}$. Its free, uncharged molecular formula is $\mathrm{C_6H_{13}N_3O_3}$; the biological L form has a specified arrangement at its chiral <carbon> atom. Like other <amino acids>, its <amino group> and <carboxyl group> can change protonation state, so a structural formula and the dominant ionic form in a solution need not look identical.<Citrulline in ChEBI>[CHEBI:18211, structure; CHEBI:16349, L-enantiomer, formula and zwitterion relation]{ref}

An illuminating experimental role is as a reaction product of <nitric oxide synthase>. A 1990 purification from rat <cerebellum> associated conversion of <arginine> to <nitric oxide> with stoichiometric production of <citrulline>. The reaction required <NADPH> and <calcium ions>, and the purified <enzyme> required <calmodulin>. Measuring newly formed <citrulline> therefore provided a chemically distinct readout of the same <enzyme> reaction that generated a gaseous signalling molecule.<Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme by D. S. Bredt and S. H. Snyder>[PNAS 87, pp. 682–685; abstract, coupled arginine/citrulline conversion and cofactor requirements]{ref}

For an idealized assay in which each turnover gives one molecule of <citrulline> and no competing reaction consumes it, formation of $10\,\mathrm{nmol}$ of <citrulline> would correspond to $10\,\mathrm{nmol}$ of <nitric oxide> generated. That inference requires the specified reaction and appropriate controls; an existing pool of <citrulline> in a <cell> is not by itself a measure of current <nitric oxide synthase> activity.