What is the biochemical basis for X-linked adrenoleukodystrophy (X-ALD)? What is the formulation of "Lorenzo's oil," and what is thought to be its mode of action?

X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder caused by a mutation in the ABCD1 gene, located on the X chromosome. The ABCD1 gene is responsible for encoding a peroxisomal membrane protein called ALD protein (adrenoleukodystrophy protein). This protein plays a major role in transporting very-long-chain fatty acids (VLCFAs) into peroxisomes, where they undergo beta-oxidation. The mutation in the ABCD1 gene leads to impaired ALD protein function and reduced transportation of VLCFAs into peroxisomes. As a result, VLCFAs accumulate in various tissues, including the adrenal cortex and the white matter of the brain. Subsequently, it triggers an inflammatory response damaging the myelin sheath surrounding the nerve cells, hence causing the characteristic symptoms of X-ALD.

Lorenzo's oil is a mixture of two fatty acids, glycerol trioleate and glycerol trierucate, in a 4:1 ratio respectively. Glycerol trioleate contains oleic acid (a monounsaturated omega-9 fatty acid), while glycerol trierucate consists of erucic acid (a monounsaturated omega-9 fatty acid). These are both long-chain fatty acids but not classified as very-long-chain fatty acids.

Lorenzo's oil is thought to function by inhibiting the elongation of long-chain fatty acids, thus reducing the production of VLCFAs. By incorporating more of the oleic and erucic acids in cell membranes and competing for the enzymes responsible for VLCFA synthesis (ELOVL1 and ELOVL2), Lorenzo's oil helps to decrease the levels of VLCFAs in the body effectively. Once VLCFA levels are reduced, the inflammatory response associated with tissue accumulation is also decreased, which may contribute to slowing down the progression of X-ALD. However, it is essential to note that Lorenzo's oil is not a cure; it mainly helps in managing and reducing the accumulation of VLCFAs in the blood.