Methionine

This story has three parts: Met salvage, catabolism, and urology. And it spans three decades of missing research.

L-Methionine (Met) is an essential amino acid. Its use is to take part in Met-RNA and protein biosynthesis, and the synthesis of S-Adenosylmethionine (SAM). In all cases it is recycled. Even when SAM is used to produce polyamines, the sulfur is recycled to Met via the Met salvage pathway. However, if you take a Met overdose -- say 1 or 2 grams orally -- the excess doesn't show in the blood for long, and is degraded or changed quickly. It appears to be well known[1] that this excess leads to an excess of sulfate which is excreted with urine. Around 1985, at least two reactions were hypothesized for excess Met -- transamination to 4-methylthio-2-oxobutanoate (MOB) and transmethylation-transsulfuration via SAM, homocysteine and cystathionine -- with inconclusive results on which is the main path[2]. The transamination reaction to MOB certainly plays a role[3] but where the sulfate comes from quantitatively (MOB or cystathionine) is still unclear, as well as the whole regulation issue in such a tightly regulated system. Possibly the location, cytosol or mitochondria, makes a difference. Meanwhile, a review elucidated the cysteine catabolic branch[4]. So, a complete characterization of the Met-catabolic pathway via transamination -- or the proof of it being irrelevant awaits the trophy-hungry lab rat.

Additionally, in the Met salvage pathway, we don't know exactly the human gene producing the necessary methylthioribulose 1-phosphate dehydratase activity (EC 4.2.1.109). From homology to yeast, it might be APIP but the human activity was never shown. And finally, while transamination to and from Met is proven, which of the many transaminases has that broad specificity to also take on Met? Our guess it's the GGT but noone bothered to test it for decades.

Finally, the sulfate excretion accounting for the acidification potential of Met[5], according to my urologist, this is the only compound with that effect on humans. There may be also ammonium chloride (ref?). Okay, there is the n=60 study[6] showing diluted vinegar being effective in urinary tract infection (UTI), but would you drink it daily to prevent infections? Surprisingly, although the beneficial effect of low pH urine for UTI prevention is beyond doubt, there is no clinical study using Met for this. It would be so easy, the pH test strips and Met itself are inexpensive, so please someone take up this piece of Unsexy Science!

Refs:
1.  Mudd, S. H., and H. L. Levy. 1983. Disorders of Transsulfuration. In: The Metabolic Basis of Inherited Disease. 5th edition. J. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, J. L. Goldstein, and M. S. Brown, editors. McGraw-Hill Book Co., Inc., New York. 522-559. (unchecked)
2. J. D. Finkelstein, J. J. Martin: Methionine metabolism in mammals. Adaptation to methionine excess. In: J biol chem 261, 4, 1986, 1582–1587. PMID 3080429.
3. W. A. Gahl, I. Bernardini et al.: Transsulfuration in an adult with hepatic methionine adenosyltransferase deficiency. In: J clin. invest. 81, 2, 1988, 390–397. doi:10.1172/JCI113331. PMID 3339126. PMC 329581.
4. M. H. Stipanuk, I. Ueki: Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. In: Journal of inherited metabolic disease 34, 1, 2011, 17–32. doi:10.1007/s10545-009-9006-9. PMID 20162368. PMC 290177. (Review)
5. D. L. Bella, M. H. Stipanuk: Effects of protein, methionine, or chloride on acid-base balance and on cysteine catabolism. In: Am J phys 269, 5 Pt 1, 1995, E910–E917. PMID 7491943.
6. Y. C. Chung, H. H. Chen, M. L. Yeh: Vinegar for Decreasing Catheter-Associated Bacteriuria in Long-Term Catheterized Patients : A Randomized Controlled Trial. In: ''Biological research for nursing'' epub 2011. doi:10.1177/1099800411412767. PMID 21708892.