BLVRA Human

The breakdown of heme, a component of hemoglobin, is a two-step process. First, heme oxygenase catalyzes the conversion of heme to biliverdin. This reaction involves the cleavage of the heme ring at the alpha-methene bridge, producing biliverdin IXα, carbon monoxide, and free iron . Biliverdin is then reduced to bilirubin by biliverdin reductase A, utilizing NADPH as a cofactor .

Biliverdin Reductase A is a multifunctional enzyme with a wide range of biological activities. It is known for its role in converting biliverdin to bilirubin, but it also has kinase activity and can function as a transcription factor . The enzyme has two distinct cofactor-dependent pH optima: in the acidic range (pH 6.0-6.7), it utilizes NADH, while in the alkaline range (pH 8.5-8.7), it utilizes NADPH .

The recombinant form of Biliverdin Reductase A is produced using Escherichia coli expression systems. This method allows for the scalable production of the enzyme, ensuring high purity and activity . The recombinant enzyme is typically expressed in a buffered aqueous solution and can be stored at -20°C .

Biliverdin Reductase A is considered a major physiological cytoprotectant. It has been shown to suppress experimental autoimmune encephalomyelitis in rats, indicating its potential role in modulating immune responses . Depletion of this enzyme leads to the accumulation of cellular oxidants and increased cell death, highlighting its importance in cellular protection .

The ability of Biliverdin Reductase A to convert biliverdin to bilirubin, a potent antioxidant, suggests its potential as a therapeutic agent. The enzyme’s role in redox homeostasis and its protective effects against oxidative stress make it a promising candidate for the treatment of various diseases, including neurodegenerative disorders and inflammatory conditions .