methionine + cysteine + taurine + glutathione (sulfur containing amino acids)
Methionine is a nutritionally indispensable amino acid required for the normal growth and development of all mammals (1, 2), whereas cysteine is conditionally indispensable (3, 4). In addition to its required role in protein synthesis, methionine supplies the methyl group for numerous methylation reactions and the sulfur atom for cysteine formation (5–8). Through the intermediate S-adenosylmethionine, methionine is the source of the methyl groups of choline, creatine, and both DNA and RNA intermediates (1, 5, 6, 8). Cysteine is involved in the protein synthesis and biosynthesis of taurine, sulfate, and glutathione (6).
so, the amino acid here that is considered essential is methionine, but it seems like the major purpose of methionine in the diet is actually to act as a source of sulfur (in conversion to cysteine) or as a methyl donor (via s-adenyl-methionine, or sam); taurine and glutathione are actually both derived more directly from cysteine, which is formed by the combination of serine & sulfur (from the methionine). it's really serine that is the precursor here, not methionine. as such, if i'm concerned about synthesizing cysteine, i need to ensure i'm getting enough serine.
serine is apparently primarily converted from glycine, but glycine is then apparently mostly converted from serine, so that doesn't help. rather, it seems like i should aim to get sufficient serine levels directly.
but, then, i should just focus on getting cysteine directly. right? yeah.
so, the main thing i'd want to do with methionine, proper, then, is use it to build s-adenosyl-methionine which is the form that methionine seems to be used as most readily. methionine also plays a role in synthesizing some neurotransmitters (including acting as a precursor to choline, where necessary), but this is a general role for amino acids, and they seem to be converted back and forth fairly easily. i'm actually going to do some more research into neurotransmitters as it's own unit topic, and may add further requirements to ensure i'm generating enough of them. for now, i'm going to assume that the rdis for the amino acids & vitamins, together, are enough to ensure i'm getting enough brain food. if i get extra methionine it could potentially end up as cysteine, but excess homocysteine (the intermediate) should be avoided - which is partly what all the extra betaine is about. b6 & b12 also help in clearing out excess homocysteine. so, i want to get a little extra methionine, but broadly keep it down a little.
so, the two main derivatives of cysteine are glutathione (with glutamic acid & glycine), which is one of the few known antioxidants that actually functions in vivo but cannot be absorbed in tact and must be synthesized, and taurine, which, due to the lack of red meat in my diet, can only be derived from cysteine. i'm phasing taurine out because i just don't get it in my diet, but i'll be working the 100 mg/day requirements into the cysteine requirements as a subcomponent.
rdi:
this is unsettled science, at this point. i've looked at a number of sources and built up the following chart:
eu: 10.4 mg/kg for methionine, 4.1 mg/kg for cysteine
usda: 19 mg/kg total
di buono 1: 21 mg/kg total + taurine & glutathione requirements
caveat:
Therefore, the total SAA requirements found in the present study represent the amount of dietary methionine needed to fulfill all the functions of methionine in vivo. However, it cannot be concluded from the present study whether the amount of cysteine required for the synthesis of glutathione, taurine, or sulfate was achieved with methionine intakes at the breakpoint for protein synthesis. This is an important consideration for deciding on appropriate dietary reference intakes for SAAs; additional research is required on this issue.
di buono 2: 10.1 mg/kg for methionine (lower bound) + 10.9 mg/kg cysteine (upper bound)
Results: The mean and population-safe (upper limit of the 95% CI) methionine requirements in the absence of exogenous cysteine were found to be 12.6 and 21 mg·kg−1·d−1, respectively. The mean and population-safe methionine requirements in the presence of excess dietary cysteine were found to be 4.5 and 10.1 mg·kg−1·d−1, respectively, representing a cysteine sparing effect of 64% in a comparison of mean methionine requirements and of 52% in a comparison of population-safe methionine intakes. Furthermore, the difference between population-safe intakes with and without dietary cysteine establishes a safe cysteine intake of 10.9 mg·kg−1·d−1 in the presence of adequate methionine intakes.
milk study 1: 36.3 mg/kg total, with a cys:met ratio of ~ 1.25
milk study 2: cys/met ratio of ~ 1.42
further sources:
2) the survey: https://academic.oup.com/jn/article/136/6/1682S/4664458
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that's a messy pile of data. some comments are necessary.
i posted this earlier:
i think a part of the reason this is confusing - and the survey states as much up front - is that the language they're using is often inexact, to say the least. the ideas are not being presented clearly. so, let me work through this and try to get the ideas clarified, first.
their argument is that cysteine can "substitute" for methionine if it's present in sufficient quantities that you can prevent the conversion of methionine to cysteine. but, this isn't actually a substitution process at all. it's more like a blocking process. they should by talking about transsulfuration-blocking, not cysteine-sparing.
they then erect this idea of "total sulfur requirement", which is the amount of methionine you need without any cysteine, and subtract out the minimum obligatory amount of methionine, which they decide is the amount of methionine you need to do methionine things. the argument is that what's left should be the amount converted to cysteine, but, as i've said before, that doesn't actually make any sense, and i'd advise against citing that deduction. i guess you could use that number as a crude upper bound, but you don't actually know how much non-essential methionine gets converted, so you can't actually say anything besides that. the amount of cysteine you need to block conversion could very well be half of that. worse, if you go back to the first study, it mentions that they don't know that the amount of methionine cited is truly sufficient for what i'm measuring - they explicitly poi\int out that that number may be insufficient to produce enough taurine and glutathione. so, you can only deduce that you need some amount that is less than 10.9 mg/kg of cysteine to block transsulfuration from occurring at levels that may or may not be sufficient to meet cysteine needs.
so, what's the right experiment, then, even if i can't find it?
what you should do if you want the answer i'm looking for is measure the maximum amount of methionine that gets converted to cysteine, and base your cysteine requirements on how much you observe your body transsulfurate. so, what you want to do is give the subject massive levels of methionine & serine with zero cysteine and zero cysteine derivatives and see where the breakpoint occurs. that will determine total dietary cysteine requirements, independent of methionine. i'd want to take that number and build an rdi for cysteine on it. then, i could subtract that out from the total sulfur requirements to get a methionine rdi.
the confusion is likely stemming from methionine being seen as essential and cysteine being seen as inessential. that may be technically true, in terms of the chemistry, but cysteine seems to be the more valuable chemical, so it should really be what the requirements are built around. methionine may be indispensable, but only at much lower levels, and only as an after thought, in the presence of sufficient cysteine.
so, i'm taking a giant step back and asking a different question - has anybody tried to measure how much total cysteine your body requires, independent of methionine? let me figure that out first...
so, the way that this has been approached up to now has generally been to look at the two of them as "sulfur containing amino acids" and try to determine the total amount of sulfur required by the body. as methionine can convert to cysteine, but cysteine cannot convert back to methionine, and specifically cannot convert to sam, methionine is labeled as "essential", while cysteine is not. unfortunately, cysteine requirements are then generally approached with the intent to minimize methionine requirements by "sparing" them, which is really a blocking process - what di buono 2 really does is determine how much cysteine you need to take before your body decides it has enough that it can stop converting methionine to cysteine, but it doesn't tell us how much cysteine we need, altogether, if we aim to minimize our methionine intake to methylation and stop transsulfuration from occurring, altogether. so, this is ultimately a very conservative argument that ignores the implication that we may have evolved these pathways - we transsulfurate in only one direction - for a good reason, and that maybe excess cysteine is a better idea than excess methionine because of it. as mentioned, excess homocysteine is bad news for your arteries; loading up on cysteine seems like a better idea. yet, it means that we need to ensure we get enough methionine in it's own right, too, because it remains essential, in the form of sam.
the second question - how much cysteine we need, altogether, if we aim to minimize our methionine intake to methylation and stop transsulfuration from occurring, altogether - is the one i'm seeking an answer to, and it doesn't seem to be a question that has been asked. rather, the question that has been asked is the third one, "what is the minimum methionine requirements in the presence of sufficient cysteine, whatever the latter is", and we have two answers:
- 10.1 mg/kg (di buono 2 ) & 10.4 mg/kg (eu)
these are relatively close, but let's take the bigger number. then,
methionine: 10.4*70 = 728 mg
to go back to the second question, then, the bounds are 4.1 mg/kg (eu) and 10.9 mg/kg (di buono 2 ). 10.9 is explicitly an upper bound, although they acknowledge that the upper bound may not be sufficient. i've previously calculated that 100 mg/day is a reasonable target for taurine production, so that should be added to the derived upper limit, whatever it's determined to be. so, these numbers are in truth only marginally useful. if nobody wants to ask the question i'm asking, what else can we do?
one thing we could do is look at human breast milk for clues.
i've found two studies, both of which determine that there is more cysteine than methionine in breast milk, which suggests that humans have indeed evolved these pathways in some sort of complicated manner; it doesn't seem to be an accident that we only transsulfurate in one direction, given that our mothers give us an excess of cysteine, and just enough methionine to act as a methyl donor. the two studies provide ratios of 1.25 and 1.42. while an upper bound of 1.5 is nice and round, i am already exaggerating by using 70 mg/kg, so let's take an average instead. then, (1.25 + 1.42)/2 = 1.335 and, adding in the 100 mg/day for taurine (https://dsdfghghfsdflgkfgkja.blogspot.com/2020/10/taurine-is-something-that-im-sort-of.html):
cysteine: 10.4*1.335*70 + 100 = 1071.88
in total, that would be: (1071.88 + 728)/70 = 25.71 mg/kg
this number is higher than any of the numbers presented, except the numbers in breast milk. however, note that (1071.88 + 728)/50 = 35.9976, so a more realistic body weight estimate takes me much closer to the sulfur levels in breast milk, which are no doubt way more than enough. at 125%, that's 1.25*(1071.88 + 728)/50 = 44.997 mg/kg, which is approaching the upper limit in the next section; 1.25*(1071.88 + 728)/55 = 40.9063636364, 1.25*(1071.88 + 728)/60 = 37.4975, 1.25*(1071.88 + 728)/65 = 34.6130769231.
after much hair pulling, i believe this is sufficient.
upper limit:
this article sets it at 46 mg/kg:
1.5*46*50/728 ~ 474%
.5*46*50/728 ~ 158%
i'm going to use the same ratio for cysteine.
1.5*46*50/1072 ~ 322%
.5*46*50/1072 ~ 107%
so,
methionine (728 mg):
per meal: >50, <158
total: >150, <474
cysteine (1072, includes taurine + glutathione):
per meal: >50, <107
total: > 150, <322
methionine
water - 0
=============
raspberry - ?. raspberries have very low amounts of amino acids, low enough that nobody bothered measuring it, or that it couldn't be measured. i have not been able to find data, but it's minimal across the board.
guava - 16*.3 = 4.8
banana - 9
strawberry - 2
avocado - 57
kiwi - 17
soy - 16*4 = 64
ice cream - 81*.825 = 66.825
yogurt - 169*.5 = 84.5
yeast - 184*5/20 = 46
vector cereal -
all bran cereal - 234*.45 = 105.3
wheat bran - 234*.07 = 16.38
sunflower seeds - 494*.08 = 39.52
flax - 370*.12 = 44.4
algal oil - 1020*.1922*.0135 = 2.646594
===============
100*(4.8 + 9 + 2 + 57 + 17 + 64 + 66.825 + 84.5 + 46 + 105.3 + 16.3 + 39.52 + 44.4 + 2.64659)/728 = 76.8257678571
cysteine
the usda has 0 for cysteine in soy milk, but that seems to be wrong. here is a different source:
h ttp s : / / w w w . r e s e a r c h g a t e . n e t / fi g u r e / D i e t a ry - so u r c e s - o f - c y s t e i ne _ tb l 1 _2 2 3 9 5 9 3 0 5
water - 0
=============
raspberry - ?. raspberries have very low amounts of amino acids, low enough that nobody bothered measuring it, or that it couldn't be measured. i have not been able to find data, but it's minimal across the board.
guava - ?
banana - 11
strawberry - 6
avocado - 41
kiwi - 21
soy - 113*1.6 = 180.8
ice cream - 29*.825 = 23.925
yogurt - 52*.5 = 26
yeast - 102*5/20 = 25.5
vector cereal -
all bran cereal - 371*.45 = 166.95
wheat bran - 371*.07 = 25.97
sunflower seeds - 451*.08 = 36.08
flax - 340*.12 = 40.8
algal oil - 1020*.1922*.0062 = 1.2154728
===============
100*(11 + 6 + 41 + 21 + 180.8 + 23.925 + 26 + 25.5 + 166.95 + 25.97 + 36.08 + 40.8 + 1.21547)/1072 = 56.5522826493
methionine + cysteine
met: (4.8 + 9 + 2 + 57 + 17 + 64 + 66.825 + 84.5 + 46 + 105.3 + 16.3 + 39.52 + 44.4 + 2.64659) = 559.29159
cys: (11 + 6 + 41 + 21 + 180.8 + 23.925 + 26 + 25.5 + 166.95 + 25.97 + 36.08 + 40.8 + 1.21547) = 606.24047
tot: 728 + 1071.88 = 1799.88,
(559.29159 + 606.24047)/1799.98 = 0.64752500583
....but i'm not measuring this.