Beta-carotene 15,15′-dioxygenase (BCO) is an enzyme that converts beta-carotene to retinal. Mutations in the BCMO1/BCO1 gene are associated with reduced function of this enzyme.
beta-carotene +O2-> 2 retinal (cofactor: iron as Fe2+)
Retinal can be converted to retinol (vitamin A), and the BCO enzyme increases vitamin A levels by conversion from beta-carotene. Decreased function in the BCO enzyme might impact the vitamin A metabolism, since beta-carotene is a source of vitamin A for the body (1). Beta-carotene content is high in red, yellow and orange vegetables and retinol is found in animal products like liver, milk or egg yolk.
Vitamin A deficiency might impact the fatty acid synthesis. Reduced activity of acetyl-CoA carboxylase, the starting enzyme of the fatty acid synthesis, has been found in the liver of retinol-deficient rats (2). The body is able to produce alpha lipoic acid by itself, via fatty acid synthesis and with SAMe. Low retinol levels could impact the body’s ability to produce alpha lipoic acid.
Alpha lipoic acid is a cofactor of the enzyme pyruvate dehydrogenase, which is needed to break down carbohydrates. Also, Alpha lipoic acid acts as an antioxidant in the body and its oxidized form DHLA (dihydro lipoic acid) is able to regenerate vitamin C, E and glutathione.
Retinol is also relevant for copper-binding by stimulating the production of the copper binding protein ceruloplasmin (3). Retinol also has benificial effects on iron status.
Mutations in the BCO enzyme might be associated with lower levels of retinal and retinol and correspondingly decrease retinol dependent processes like the fatty acid synthesis and alpha lipoic acid or ceruloplasmin production.
Cofactors and pathways:
Thyroxine and bile acids enhance BCO function. Oxygen and iron (as Fe2+) are cofactors in the beta-carotene oxygenase. Hemoglobin transports oxygen in the blood and supplies the cells with oxygen. It is produced with heme and Fe2+. Because oxygen catalyzes the reaction of the BCO enzyme, I think, there might be a relationship between the heme synthesis pathway, hemoglobin levels and BCO function.
The heme synthesis starts with succinyl-CoA and is dependent on vitamin B6, B2, zinc and Fe2+. Succinyl CoA is produced in the citric acid cycle or via breakdown of odd-numbered fatty acids. The heme synthesis depends on these cofactors, but I don’t have good experience with taking all of them to increase the heme pathway function.
This is only my personal feeling, that hydroxocobalamin might be associated with iron and retinol status. The coenzyme form adenosylcobalamin helps convert propionyl-CoA to succinyl-CoA and might increase heme synthesis like that. Zinc might also be relevant as a cofactor of the heme synthesis and because it is needed to produce the retinol-binding protein (4).
Iron would be the obvious cofactor for BCO and sufficient levels might be needed to ensure good function, but supplements might not be tolerated well. Iron can increase lipid peroxidation which impacts the antioxidant status, especially in people with chronic illness. That could be overall contraproductive.
In my opinion, mutations of the beta-carotene 15,15′-dioxygenase belong to the mutations, that have the ability to influence metabolic function, like MTHFR or MTR/MTRR mutations. Because the activity of this enzyme relates to the level of a vitamin -retinol-, low activity of the BCO can have consequences of vitamin A deficiency and reduce key functions in the metabolism, like the fatty acid synthesis.