Lower B12 Transport Mechanim from Infection Identified-- Does it Parallel MCS?

Background: Inflammatory activities in the gut may influence neuroinflammatory cytokines in the brain to influence behaviors. In the brain and other organ systems including the intestines, efflux pumps help to minimize the damage done to tissue from xenobiotics and other molecules by transporting across biological barriers to reduce the "waiting" time for cytochrome enzymes to break them down to make them more excretable . ABC transporters are an example of these pumps and their presence or absence can alter the excretion rate of harmful drugs and other toxins as well as, potentially determine the level of tissue damage from environmental toxins.

A new study provides evidence that the MRP1/ABCC1 transporters are important for proper metabolic balance of B12 in addition to other conjugates including sulfates and glutathione. We have previously noted how certain metabolic pathways are dependant on the availability of B12 and in B12-deficiency, impairments in the renal excretion of ammonia and elevations in homocysteine may occur to cause tissue damage. In general, the availability of B12 is invaluable because low levels may cause health effects in the blood and neurological problems. Studies on MRP1 knock-out mice, "confirm the ability of MRP1 to mediate ATP-dependent Cbl transport and the physiologic role of MRP1 in mammalian Cbl homeostasis is indicated with disruption of MRP1. These animals have a reduced concentration of Cbl in plasma and in the storage organs liver and kidney." On the other hand, the class of efflux transporters are important for proper detoxification of 50% or more of the prescription drugs on the market. Certain bacterial infections can upregulate the expression of these transporters and therefore they may play a role in functional diseases of the intestines, unexpected results of medical therapies and contribute to drug interactions and potentiate effects of shutting off the antioxidant system from altered GSK-3b signals.  MRP transporters are critical components in olfaction and their disfunction may lead to tissue damage and aberrant neural signaling of the olfactory secondary pathway may alter neurotransmission, therefore, it is not beyond the bounds of reason to assume MRP signaling may influence MCS through regulation of evolutionary olfactory pathways of IGF-1, BDNF, etc.


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