I'm just doing a little exercise looking at the metabolism of aspartame in the body, wondering whether there is anything concerning there and I have a small question. Aspartame is metabolised into phenylalanine, aspartate and methanol in the small intestine. For all intents and purposes only the methanol is of concern, the other compounds are amino acids that are much more plentiful in our ordinary diet. I calculated that in with a can of coke zero of 87mg, 0.3 mmol of methanol (or 9.6 mg) enters the portal circulation to be metabolised by the liver. The volume of distribution of methanol is 0.7 L/kg. At most adult body weights, this volume of distribution leads to 0.15 - 0.22 mg/L concentration of methanol. The liver's enzymatic breakdown to formic acid is about 8 mg/dL/h (https://www.ncbi.nlm.nih.gov/books/NBK482121/). So we should be able to metabolise all the methanol from a can of coke zero, if we drank it all in one gulp in less than 15 seconds.
My question now concerns how much formic acid remains in the body, because I'm unsure how formic acid is excreted, apparently it "accumulates". However, the pKa of formic acid is 3.75. If the intracellular pH of the hepatocyte is around 7.0 then does that mean the ratio [formate]/[formic acid] should be around 10^(7 - 3.75) to 1 right? The problem of formic acid is that it inhibits cytochrome C oxidase (complex IV of the ETC) and has other toxic effects, whereas formate can be readily metabolised by folic acid into CO2 and water. Presumably a saturation of this action of folate is what contributes to formic acid overload in methanol toxicity.
Are my calculations so far correct though? Should I feel safe ingesting the 87mg of aspartame because the toxic formic acid is mostly converted to formate?
My question now concerns how much formic acid remains in the body, because I'm unsure how formic acid is excreted, apparently it "accumulates". However, the pKa of formic acid is 3.75. If the intracellular pH of the hepatocyte is around 7.0 then does that mean the ratio [formate]/[formic acid] should be around 10^(7 - 3.75) to 1 right? The problem of formic acid is that it inhibits cytochrome C oxidase (complex IV of the ETC) and has other toxic effects, whereas formate can be readily metabolised by folic acid into CO2 and water. Presumably a saturation of this action of folate is what contributes to formic acid overload in methanol toxicity.
Are my calculations so far correct though? Should I feel safe ingesting the 87mg of aspartame because the toxic formic acid is mostly converted to formate?
