Among the antioxidant genes activated by Nrf2, one of the most commonly studied is the heme oxygenase 1 (HO-1) gene which converts free heme, which has prooxidant effects, into iron, carbon monoxide (CO), and biliverdin
, with the last being converted into the antioxidant bilirubin via an activity also raised by Nrf2, the two biliverdin
Heme-oxygenase (HO) 1 and 2 are the rate-limiting enzymes in the catabolism of heme, a reaction that yields equimolar amounts of biliverdin
reductase-A (BVR-A) is a pleiotropic enzyme that not only catalyzes the synthesis of the powerful antioxidant bilirubin but through its Ser/Thr/Tyr kinase activity modulates cell signaling networks including the two main arms of insulin signaling: MAPK and PI3K.
Further breakdown releases biliverdin
(green) and finally, bilirubin (yellow).
A growing number of studies have found a positive correlation between blue biliverdin
and either maternal or egg quality (Morales et al.
In a previous study, it has been shown that bilirubin undergoes redox cycling with biliverdin
, which is subsequently reduced by biliverdin
reductase to regenerate bilirubin (63).
The "haem" bit of the haemoglobin contains a single atom of iron, which goes through many transformations as it gets broken down, through bilirubin and biliverdin
is then processed to form bilirubin (see figure 1, opposite page).
Heme oxygenase converts heme to bilirubin and biliverdin
Heme oxygenase degrades the heme to release iron, carbon monoxide, and biliverdin
, and the latter is reduced to bilirubin.
Bilirubin benefits: cellular protection by a biliverdin
reductase antioxidant cycle.
It is made by enzymes breaking down the red haem molecule (found in haemoglobin in red blood cells) into green biliverdin
and yellow bilirubin molecules.