Nitric oxide and intracellular heme.
Figure 2 depicts a working hypothesis for these results. Activation of .NO synthesis results in nitrogen oxide-induced loss of protein-bound heme from CYP proteins, which remain relatively intact. This heme liberation results in a decrease in heme synthesis (decreased ALAS) and an increase in heme degradation (increased HO). In addition, .NO synthesis results in direct inhibition of ferrochelatase, which further contributes to inhibition of heme synthesis. There also appears to be a mechanism to repair or resynthesize CYP after .NO synthesis is inhibited. Finally, a result of this effect may be protection against cellular injury, since increased HO is an important response against cellular injury from a variety of insults.
Kim
Y M
YM
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261, USA.
Bergonia
H A
HA
Müller
C
C
Pitt
B R
BR
Watkins
W D
WD
Lancaster
J R
JR
D000818:Animals; D002374:Catalase / Q000096:biosynthesis; D003580:Cytochromes / Q000096:biosynthesis; D006418:Heme / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*
D003580:Cytochromes; D009569:Nitric Oxide; D006418:Heme; D002374:Catalase