Vitamin D is nothing without hydroxylation, which is carried out by hydroxylase enzymes in the liver and kidney. (Not to be confused with Hydrolase enzymes) Hydroxylation is the process that makes the Cytochrome P450 system work and oxidizes those things that would otherwise makes us ill. It is also essential for biosynthesis and metabolism of all hormones/prohormones including those that largely affect our voluntary energy expenditures--all the catecholamines, VitD, cortisol, they all will be affected by impaired hydroxylation; it is seemingly of great importance to keep the control of oxidizing bad stuff and synthesizing energy together because global decreases in hydroxylation will affect so many processes related to the regulation of oxidative stress. As an example of decreased hydroxylation, you have something like congenital deficiency of 21-Hydroxylase, which causes adrenal insufficiency, salt wasting, etc., sounds a bit like "adrenal fatigue," don't you think?
Vitamin D completely lacks biological activity until hydroxylation. It simply has no significant effect on humans until it is hydroxylated. Hydroxylation is also critical for amine metabolism. With enhanced hydroxylation, one can more efficiently process hydroxyl groups, which are just groups that contain an Oxygen molecule bound to a Hydrogen molecule, but there is a special problem caused by a particular kind of hydroxyl group with a different charge called the "hydroxyl radical." This is something we have to deal with in abundance due to our existing poor ability to suppress oxidative stress combined with our high NOS/ROS burden. Hydroxyl radicals are highly reactive molecules that destroys your proteins, your fats, your DNA. This molecule doesn't stay around long, but it causes lots of problems. As you may have guessed, endotoxins are also negatively charged and generate their own hydroxyl radicals.
A number of these hydroxylase enzymes are particularly notable, including the aromatic amino acid hydroylase enzymes. This includes tyrosine, phenyalanine, and trypophan and thus influences a whole host of critical biologic molecules that are metabolized from these. Energy, hormones, sleep, mood obviously have the potential to be affected. All the stress hormones and melanin are produced from phenylanine. I think I mentioned that i felt that the dark circles under many peoples eyes (particularly when they experience the effects of circulating endotoxins) is related to the cellular debris from microbial organisms that metabolize phenols because the byproduct is melanin. In effect, I think there is biological role for these organisms that can decompose melanin, which suggests we have high concentrations of phenolic and related compounds. A similar condition, at least biochemically and symptomatically, hepatic encephalopathy, also demonstrates an accumulation of aromatic amino acids and a scarcity of BCCA. This is also a condition where elevated plasma ammonia is nearly universal; actually it shares countless similarities with ME/CFS among a number of notable differences. Of course, I think the evidence of hepatic dysfunction in ME/CFS is growing, and any GIT syndrome is going to affect the liver. One of theories regarding the pathogenesis of hepatic encephalopathy relates to an accumulation of phenols.
Looking at the aromatic amino acids, which require hydroxylation, tyrosine, has that same -OH (hydroxyl) group. It just so happens Bifidobacteria are really good at getting rid of phenolic compounds, like tyrosine. Salicylates are phenolic compounds, as are those neurotransmitters that come from phenylalanine. Toxic compounds like cresols, another phenolic compound, accumulates in those with lower counts of Bifidobacteria, and these accumulations are not trivial. Tryptophan, well you know that this is the precursor to serotonin, I will not discuss this one now, but you can extrapolate the consequences this may create.
What about the stuff that I really don't like, threonine. Makes me feel awful, involved in maintaining intestinal integrity. It's metabolism is closely tied to serine, cysteine, glycine, active site for VDR deglycosylation by N-acetylgalactosaminadase occurs at a threonine residue. Threonine has an -OH (hydroxyl) group, and it is incorporated as part of a set of critical enzymes called the serine/threonine-specific protein kinase group, these actually carry out phosphorylation functions, including phosphorylation of the vitamin D receptor.