So I have recently been traveling, and I have a theory about BH4 that I'm excited about. First, the story:
I live in Portland OR. When I first started taking it, I could only take about...maybe 1-2.5 mg BH4 per day, at which point I would get a headache. Then I started taking B6 (I had been taking a lot of things, but on purpose, no B6). To avoid what can become a fairly serious depression as well as diarrhea, I need to take about 2 parts BH4 to 1 part B6. For the past month or so I have been taking 8 mg B6 and 16 mg BH4, divided into four doses daily.
Then I went to Denver, CO. Suddenly, no matter that I was still taking the B6, I could not take BH4 without getting a headache. Also, I began getting diarrhea. When I first started the B6, I got diarrhea, which I fixed by taking one sixth of the dose (15 mg) six times a day. I have CBS C699T+/+, so I assume that B6 will end up creating a fair bit of ammonia and sulfites for me. The sulfites seem to be dealt with via molybdenum, so my assumption is that the diarrhea came from excess ammonia, particularly as the BH4 plus the divided dose of B6 seemed to prevent that.
The final piece of the picture is my history with colorado: In the past eight years, I have lived in both oregon and colorado, and I have traveled (mostly from oregon to colorado) at least once, if not multiple times in a year. Each time I travel from oregon to colorado, a few changes to my health are to be expected: First, a mild depression that I associate with wet weather lifts. Second, my sleep gets worse. Third, I have periodic diarrhea.
Based on this, I theorize that BH4, while necessary to the function of NOS when converting arginine to citrulline + NO, does not use BH4. This seems to be what all the studies agree on. I would continue to theorize that when converting citrulline + NO to arginine, it does use BH4. I suspect Yasko has seen some sort of study indicating this that we haven't found. Finally, I theorize that a difference in humidity, and possibly air pressure, change the body's need for NO, causing--in my case--NOS to switch what reaction it catalyzes based on climate.
This would potentially explain why some people, in spite of getting enough vitamin D (I had a friend like this) always feel a little depressed in wetter climates.
Has anyone had similar experiences? Nandixon, does your expertise cover this? Is it possible for an enzyme to use a cofactor when moving a reaction in one direction, but not in another?