Monday, 11 December 2017

human biology - Are there any effects of elevated Cysteine levels on cognitive function?


I'm looking at this diagram of homocysteine metabolism and see two distinct pathways that the amino acid may get metabolized to: with vitamin B12 it gets converted back into methionine, while with B6 it gets converted to cysteine.


I've followed the links for the products that Cysteine gets metabolized to and could not find any references to cognitive effects. Are there any cognitive effects of Cysteine or other amino acids that it gets metabolized to?


Diagram of homocysteine metabolism


I'm interested in learning what are the possible effects of pharmacological (50mg - 100mg) doses of vitamin B6 on this metabolic cycle, while folate and B12 levels stay at the baseline levels. It seems to me that if vitamin B6 is more readily available, there will be a higher chance of homocysteine metabolized into Cysteine. Is this assumption correct? What are the implications to this metabolic cycle that may be caused by elevated levels of vitamin B6, while keeping folate and B12 at baseline levels?


I'm particularly interested in the implications of this process on dreaming. There has been numerous reports among dreamers that 50-100mg of vitamin B6, taken in the 3rd-5th sleep cycle produces very intense and vivid dreams, sometimes featuring spontaneous awareness (lucid dreams), while B-complex vitamins (B6, B12, Folate, Niacin, etc) appear to produce the opposite effect - very vague dream recall.


I'm trying to understand if there is indeed a connection between the metabolic pathway that homocysteine may take and the vividness of dreams, capacity to recall them clearly and the phenomenon of being able to spontaneously realize the fact that the person is dreaming while still asleep.


Thank you for your input!



Diagram obtained from here



Answer



Your shown homocysteine pathway is way too simple. Especially the production of the neuromodulator H2S from excess sulfur amino acids is not shown. In the last years many more enzymes and reactions have been discovered. I have summarized human sulfur amino acid metabolism in reactome.org, so please use this link to discover all the details and new papers. I'll also append some of the relevant papers below.


Brosnan, JT, Brosnan, ME The sulfur-containing amino acids: an overview 2006 J Nutr PMID 16702333


Remethylation of homocysteine to methionine can also happen using betaine as a methyl donor. This reaction is also part of choline catabolism.


Li, F, Feng, Q, Lee, C, Wang, S, Pelleymounter, LL, Moon, I, Eckloff, BW, Wieben, ED, Schaid, DJ, Yee, V, Weinshilboum, RM Human betaine-homocysteine methyltransferase (BHMT) and BHMT2: common gene sequence variation and functional characterization 2008 Mol Genet Metab PMID 18457970


Bearden, SE, Beard RS, Jr, Pfau, JC Extracellular transsulfuration generates hydrogen sulfide from homocysteine and protects endothelium from redox stress 2010 Am J Physiol Heart Circ Physiol PMID 20817827


Dominy, JE, Stipanuk, MH New roles for cysteine and transsulfuration enzymes: production of H2S, a neuromodulator and smooth muscle relaxant 2004 Nutr Rev PMID 15497768


Stipanuk, MH, Ueki, I Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur 2011 J Inherit Metab Dis PMID 20162368


Chiku, T, Padovani, D, Zhu, W, Singh, S, Vitvitsky, V, Banerjee, R H2S biogenesis by human cystathionine gamma-lyase leads to the novel sulfur metabolites lanthionine and homolanthionine and is responsive to the grade of hyperhomocysteinemia 2009 J Biol Chem PMID 19261609



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