The glycerol-3-phosphate shuttle is one of the shuttles that can transfer NADH/H+ into the mitochondria. NADH/H+ itself cannot pass from the cytosol into the mitochondria through the mitochondrial membrane. In the cytosol glycerone phosphate/ dihydroxyacetone phosphate can convert NADH/H+ to NAD+, forming glycerol-3-phosphate, glycerone phosphate takes up two hydrogen from NADH/H+, which makes it glycerol-3-phosphate. Glycerol-3-phosphate can then transfer the hydrogen at the mitochondrial membrane, converting FAD to FADH2 in the respiratory chain complex II. FADH2 then pass on the 2 hydrogen to Coenzyme Q10, producing QH2.
(click on image for large version)
The glycerol-3-phosphate shuttle is important to prevent a rise in cytosolic NADH/H+ and to activate the respiratory chain. High NADH/H+ in the cytosol can increase lactate levels. If NADH/H+ isn’t being converted back to NAD+, NAD+ in the cytosol is low and this inhibits the glycolysis, which requires NAD+. The FAD-dependent part of glycerol-3-phosphate dehydrogenase is activated by (mitochondrial?) calcium. The FAD-dependent enzyme is a mitochondrial dehydrogenase (1). This is another important function of calcium signaling.
α-Glycerylphosphorylcholine is a choline form. It is produced from phosphatidylcholine with the enzyme phospholipase A2. Phospholipase A2 is activated by calcium and UV-light. α-Glycerylphosphorylcholine can then be converted to choline by glycerophosphocholine phosphodiesterase (2,3):
Glycerophosphocholine + H2O -> choline + glycerol-3-phosphate
(full choline metabolism in ‘info-> choline metabolism’)
α-Glycerylphosphorylcholine can release glycerol 3-phosphate, which can form FADH2 at the mitochondrial membrane. This can raise respiratory chain function, but more glycerol 3-phosphate might also increase the backward reaction to glycerone phosphate and NADH/H+ (the reaction can go both ways (4)). This might lead to more lactate production from pyruvate and NADH/H+ and a rise in lactate levels. Lactate can have pros and cons. Lactate can be brought to the liver through the blood, and be converted to glucose in the liver via gluconeogenesis. Glucose can produce glycogen, which is an important energy store in muscles and the liver. The body cleaves glycogen back to glucose when blood-sugar drops.
High lactate production can be problematic too though, because it is related to high cytosolic NADH/H+ and low aerobe metabolism. When lactate is high, pyruvate isn’t converted to acetyl-CoA anymore and doesn’t support citric acid cycle and respiratory chain function. This leads to an energy-deficit and symptoms of high lactate.
α-GPC and Calcium
Choline derived from α-glycerylphosphorylcholine can stimulate phospholipase C in some cell-types, sometimes directly, or as acetylcholine. This raises excretion of calcium from the endoplasmatic reticulum/ calcium storage into the cytosol and mitochondria and increases intracellular calcium.
I have been taking choline as choline bitartate for a while and had some mixed reactions. It helped a bit with some cognitive symptoms and sensory overload, but also induced weakness and feelings of hypoglycemia at times. I am now trying α-GPC, as I think that some of the effects of α-GPC that choline bitartrate doesn’t have, might be important. I’ll see whether I tolerate it better than choline bitartrate. I think the tolerance of α-GPC might depend on the individual situation and might be worse if calcium and lactate levels are high.
I have had some issues with low calcium and I don’t think my lactate is very high. I read somewhere that lactate can help with cognitive function, probably because glycogen can provide glucose for the blood and glucose is very important for supplying the brain with energy. My energy levels can go down pretty quickly when trying to learn something new or having to visualize images. I didn’t have these symptoms a few years ago.
It might be important for both directions to work sufficiently, lactate production and pyruvate dehydrogenase activity, so that the body can switch when needed.
A list with α-GPC content in foods here.
Update: Currently not taking α-GPC. I think α-GPC might mediate some effects of high calcium, but not work as a supplement. α-GPC in doses around 600mg made me more confused and panicked.