when both dopa and other amino acids are infused IV, is that the presence of elevated levels of phenylalanine and the large aliphatic amino acids isoleucine and leucine in plasma are preventing transport of plasma dopa into the brain. This is because they share a common molecular transport system and are competing with one another to pass through. I would guess that tyrosine and tryptophan, amino acids with large, aromatic "side chains" would have the same effect if present at similar levels. I seem to remember that all five of these amino acids, including dopa, use the same or overlapping transport systems, unlike the other amino acids like glycine and alanine which enter the brain via different transport systems. In typical dietary proteins, tyrosine and tryptophan are present in lower amounts than phenylalanine, leucine and isoleucine, and would therefore provide less competention for a common transport system.

Think of the presence of separate turnstiles or revolving doors constructed to allow only people with certain body shapes or sizes to pass through. So, if there were only one or two dopa-shaped people and several hundred phenylalanine-, leucine-, isoleucine-, and ten or twenty tyrosine- and tryptophan-shaped people all simultaneously trying to get through the same turnstile, the dopa-shaped people would get in quicker after the crowd of other amino acid folks thinned out.

However, that explanation alone does not seem to fully answer the mysterious ons and offs that folks experience even in the absence of oral dopa intake. It is well-known that dopa is made in other parts of the body, especially the adrenal medulla, as well as in non-brain dopaminergic neurons. It is my understanding that the dopa made in these cells can not get out into the general body circulation where it might otherwise supply some amount of "rescue" dopa to account for an improved pre-off condition. The gradual production of dopa by the few remaining dopaminergic neurons while in the unmedicated state, as suggested by rick and others, seems to me to better account for that phenomenon.

Robert

Could we possibly be dealing with a drop in dopamine levels brought on by a depletion of the raw materials triggered by sinemet? For example, Ron takes a sinemet and floods his system with l-dopa. As the l-dopa is used up, it might trigger the adrenals to use the tyrosine or even dopamine itself in anticipation of the oncoming symptoms to produce epinephrine and norepinephrine. It could even be a learned response- i.e. the adrenals think "Oh darn, here comes that paralysis again!" and it sets up a self-reinforcing loop. Sort of a miniature fight-or-flight response.

Robert,
Your info. on transport systems is interesting.
My major problem at present is the total off following any on, whether from oral levodopa or a "mysterious" on. I started to take tyrosine about 2 months ago, in the hope that it would facilitate own levodopa synthesis which would avoid dyskinesia. Could this be causing my dreadful offs following an on?? Am I creating a traffic jam?
Concerning body dopamine, this is used as a hormone to regulate heart rate, and in theory should not be able to cross the BBB. However, you are obviously familiar with chemical structure, so compare dopamine which "can't pass the BBB" with levodopa which can. Dopamine is very similar to levodopa, differing only by a molecule of CO2. In fact dopamine is a smaller molecule than levodopa, and combine this with the fact that PWP have dysfunctional BBB's, means that our mysterious ons could be caused by hormonal dopamine leaking into the brain from the body.