$ Why Nitric Oxide ?

& Inorganic gas - Internal air population

& A unpaired electron N=O ·

h (di)oxygen in its various redox form

h with transition metal ions

& Rapidly react with other molecules

& Easily pass through membranes

& A double-edged sword: Messenger and Toxin

& Production and Regulation: Nitric Oxide Synthase

Joan B. Mannick, Koichiro Asano, Kenneth Izumi, Elliott Kieff, and Jonathan S. Stamler

Cell, Vol. 79. 1137-46, December 30 1994

$ Nictric Oxide Synthase:

& Large (~300kDa) and complicated enzyme

& Three cosubstrate: L-arginine, NADPH, O2

Five cofactor or posthetic groups: FAD, FMN, Calmodulin, Tetrahydrobiopterin and

Heme

& Significant homology to NADPH cytochrome P450 reductase:

Two enzymes fused: a cytochrome reductase & a cytochrome

& Two isoforms:

Constitutive NOS (cNOS):

Ca²⁺ /CaM dependent

Endothelial & neuronal cells

Low levels of NO for servoregulatory service

Inducible NOS (iNOS):

Ca²⁺ /CaM independent

Induced by cytokines stimulation

high levels of NO for bacteriostatic and tumoricidal

$ Summary:

& Human B cell lines produce constitutively and very low level of NO/NOS

& EBV reactivation can be inhibited by NO in

B cell lines that express EBV latent gene products or

newly infected adult perpheral blood or umbilical core blood mononuclear cells

& Apoptosis of B cell lines can be inhibited by NO

Nathan, C., Cell Vol. 78:915-18 (1994)

Stamler, J.S. Cell Vol. 78:931-36 (1994)

Schmidt, H.H.H.W. Cell Vol. 78: 919-25 (1994)

Schmidt, H.H.H.W. Cell Vol. 78: 919-25 (1994)