Any thoughts on Citrulline malate in Pre/workout drinks?
To answer this question, we need to consider the actions of citrulline. The first is its action as a neurochemical.
Nitric Oxide and glutamate neurotransmitter receptors
A. Glutamate Receptors:
ligand gated ion channels
2 types, characterized by pharmacology:
a. NMDA: Na+ and Ca+2, slow response, requires glutamate and glycine
b. Kainate: Na+, fast response, requires glutamate only
(both kinds co-mingle in same postsynaptic membrane)
B. nitric oxide (NO)
small, highly diffusible substrate
N-hydroxy-L-arginine > NO + L-cirtulline by NOS (nitric oxide synthetase)
NO produced in POST-synaptic cell
NOS activated by Ca+2 through NMDA receptor
Oh fucking oh. Ca+2 is modulated by glutmate/NMDA receptors in brain and CNS..
So, for CNS nerve activity in brain and body, two types of chemistry drive neurochemistry: ATP and Ca+2, for the two dominant ion-gated channel types (ACh = acetylcholine and glutamate)
Now comes the hammer: citrulline, arginine and glutamate metabolism are HIGHLY interconnected. From wikipedia:
"Arginine is synthesized from citrulline by the sequential action of the cytosolic enzymes argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL).
This is energetically costly, as the synthesis of each molecule of argininosuccinate requires hydrolysis of adenosine triphosphate (ATP) to adenosine monophosphate (AMP); i.e., two ATP equivalents.
*important note: if you have FUCKED UP GLUCOS METABOLISM, you are ATP IMPAIRED. THIS DIRECTLY EFFECTS ARGININE <--> CITRULLINE <---> GLUTAMATE interconversion. (leads to a pile up citrulline and glutamate)
Citrulline can be derived from multiple sources:
* from arginine via nitric oxide synthase (NOS);
* from ornithine via catabolism of proline or glutamine/glutamate;
* from asymmetric dimethylarginine (ADMA) via DDAH.
The pathways linking arginine, glutamine, and proline are bidirectional. Thus, the net utilization or production of these amino acids is highly dependent on cell type and local metabolic demands.
On a whole-body basis, synthesis of arginine occurs principally via the intestinal???renal axis,
wherein epithelial cells of the small intestine, which produce citrulline primarily from glutamine and glutamate, collaborate with the proximal tubule cells of the kidney, which extract citrulline from the circulation and convert it to arginine, which is returned to the circulation.
Consequently, impairment of small bowel or renal function can reduce endogenous arginine synthesis, thereby increasing the dietary requirement.
ONE FUCKING HALF OF THE ADULT POPULATION HAS THIS PROBLEM BY AGE 40 and > 20% HAVE THIS PROBLEM IN THEIR EARLY 20. Arginine/citrulline supplementation is a double edged sword. If YOU FUCKING CAN"T CONVERT CITRULLINE TO ARGININE, YOU CRANK OUT MEGA QUANTITIES OF GLUTAMATE.
You also upregulate ACh activity, and thus ---> excitotoxic neurochemistry in brain and body. This has important consequences.
--> Kenwood knows this, this is the problem he is having with his NO-inducer addiction.
Synthesis of arginine from citrulline also occurs at a low level in many other cells, and cellular capacity for arginine synthesis can be markedly increased under circumstances that also induce iNOS.
Thus, citrulline, a coproduct of the NOS-catalyzed reaction, can be recycled to arginine in a pathway known as the
citrulline-NO or arginine-citrulline pathway. I mention this above, in the CNS activation discussion.
"This is demonstrated by the fact that in many cell types, citrulline can substitute for arginine to some degree in supporting NO synthesis. However, recycling is not quantitative because citrulline accumulates along with nitrate and nitrite, the stable end-products of NO, in NO-producing cells "
Bottom line: for a fairly large subset of the population with normal glucose metabolism and a lack of predominating excitatory (cause by an apparent inborn problem with glutamate translocation and norepinephrine supersensitivity to stress, which releases glutamte and Ca+2 in excessive quantities in the brain, gut, kidneys and body CNS), then citrulline supplementation will be salutory - in ortherwords, beneficial, when not used excessively.
For a smaller subset of the population that has excitatory neurochemical issues, this is not good chemical karma. At best, it should be used sparingly, at worst, avoided completely.
I hope you can follow this argument. Its an important one to consider for use of both NO-inducers and citrulline malate.
