Showing posts with label methionine. Show all posts
Showing posts with label methionine. Show all posts

Vitamin U and acne, dandruff and eczema

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Acne, dandruff and eczema are skin conditions the origins of which are often idiosyncratic and mysterious. However, one characteristic shared by all three conditions is low glutathione levels. Glutathione is by far the most important antioxidant in the human body, yet we absorb little of it from our food- that's why our body makes it. 

There are three main causes of low glutathione - 

1. A medical condition that drains large amounts of glutathione

2. A genetic block that prevents the biosynthesis or regeneration of glutathione

3. Not enough glutathione precursors in our diet

Identifying the root cause of your skin condition is an important first step in the healing process. However, this is easier said than done. Often we just don't know why these conditions happen. Sometimes they can break out suddenly and worsen quickly, particularly under stress. At other times, symptoms can persist chronically for years.

Irrespective of the root cause, restoring your glutathione levels is a vital part of this rebalancing act. Glutathione is a tripeptide comprised of cysteine, glutamate and glycine. Of these amino acids, cysteine is most commonly in short supply. If glutathione levels are low due to dietary factors, it is usually due to a shortage of cysteine. Cysteine is found in protein, especially that derived from animals. Cysteine is also made from methionine, again abundant in animal proteins. These sulfur amino acids are also plentiful in grain proteins. However, some people find that meat/dairy/grain are inflammatory for other reasons like hormones or allergens. 

Vitamin U is S-methylmethionine, a soluble nutrient abundant in vegetables and fruit that is converted into methionine by the enzyme BHMT2. There have not been any direct studies into whether Vitamin U has any effect on these three conditions, whether taken internally in the diet or as a supplement, or when applied topically as an active component of a lotion. However, taking Vitamin U can help restore glutathione levels which are low in the tissues affected by acne, dandruff and eczema, so it is quite likely that increasing your intake of Vitamin U will help with these conditions, especially in combination with the identification and removal of triggers of these conditions in you. 

A glass of freshly-made vegetable juice every day is an excellent way to boost your Vitamin U intake along with a slew of vitamins and minerals essential for good skin health. For those who prefer a supplement, one capsule per day of Bioremediation's Vitamin U may be a useful alternative.

Take care and good luck,


The methionine cycle and Vitamin U

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Summary - The methionine cycle is a multistep enzymatic process than enables Vitamin U to be used as a source of methyl groups vital for gene regulation and the regeneration of creatine/ATP in muscles, as well as its use as a precursor of glutathione required to fight oxidative stress and inflammation.

This is a simple depiction of the four-step methionine cycle in our body. In the first step, the adenosyl group of ATP is transferred to methionine to form S-adenosylmethionine (SAM), thereby activating the methyl group of methionine. In the second step, SAM donates its methyl group to a range of acceptor molecules (notably DNA, guanidinoacetate, and phosphatidylethanolamines), also yielding S-adenosylhomocysteine (SAH). In the third step, the adenosyl group SAH is removed by hydrolysis leaving homocysteine. In the fourth step, homocysteine is either remethylated using one of three methyl donors to reform methionine (step 4a) or is directed into the transsulfuration pathway to form cystathionine (step 4b).

The methionine cycle has a myriad of functions including -

1. The generation of methylation capacity, 
2. The biosynthesis of cysteine as a component of proteins and glutathione, and as a precursor to taurine and hydrogen sulfide, 
3. The biosynthesis of polyamines from SAM. 

The most important function of the methionine cycle is to generate methylation capacity. A measure of our body's methylation capacity is the SAM:SAH ratio, i.e. the relative amounts of the two intermediates. If this ratio is low (below 4), the first enzyme in transsulfuration (cystathionine beta synthase) will have low activity and homocysteine will be remethylated to reenter the methionine cycle (step 4a). This tendency will continue until the ratio is above 4, at which point the relatively high concentration of SAM activates cystathionine beta synthase (CBS) resulting in excess homocysteine being funneled into the transsulfuration pathway. 

Another important function of the methionine cycle is the biosynthesis of cysteine via transsulfuration. Transsulfuration adds cysteine to that obtained from our diet as a component of protein (~50%). Cysteine is used as a building block in human proteins, is the catalytic center of the master antioxidant glutathione as well as acting as a precursor to molecules such as taurine and hydrogen sulfide. Increased oxidative stress will result in activation of CBS activity via allosteric binding by glutathione and transcriptional upregulation by hydrogen sulfide, nitric oxide and carbon monoxide. However, despite the negative health effects of high homocysteine levels (associated with cardiovascular disease) and low glutathione levels (associated with inflammation), the maintenance of methylation capacity trumps that of the provision of transsulfuration products.

The most common cause of a low SAM:SAH is a shortfall in the supply of dietary methyl donors. Other causes of low flux include shortages in vitamins that help catalyze reactions (e.g, folate, B12, B6), mutations in genes that encode enzymes involved in catalysis (e.g. MTHFR, CBS), and very low calorie diets.

There are several nutrients that can contribute methyl groups to the methionine cycle. Aside from methionine, which enters the methionine cycle directly, the other dietary methyl donors enter the methionine cycle via methylation of homocysteine. There are three enzymes known to catalyze this reaction in humans, with each enzyme acting upon a single methyl donor molecule. Other molecules that can contribute methyl groups must do so indirectly. Consequently, the three classes of dietary methyl donor are characterized by the enzyme that catalyzes the reaction with homocysteine and its substrate -

1. Betaine:homocysteine methyltransferase 1 (BHMT1) and betaine (trimethylglycine or TMG)
2. Methionine synthase (MS) and folate (5'-methyltetrahydrofolate or MTHF)
3. Betaine:homocysteine methyltransferase 2 (BHMT2) and Vitamin U (S-methylmethionine)

Betaine (trimethyl glycine) has three methyl groups, one of which is transferred to homocysteine to form methionine and dimethyl glycine. The other two methyl groups contribute to methylation, though via assimilation through the folate cycle. Dimethyl glycine dehydrogenase catalyzes the transfer of a methyl group from dimethyl glycine to tetrahydrofolate to produce 5, 10-methylenetetrahydrofolate. The other product, methyl glycine (sarcosine) yields the last methyl group to tetrahydrofolate in a similar reaction catalyzed by the homologue sarcosine dehydrogenase.

Betaine is plentiful in whole grains, with the notable exception of rice (betaine is an osmoprotectant in plants and it appears that under the wet conditions in which rice is usually grown betaine formation is suppressed). Betaine is also produced in our body from choline, which is abundant in the fatty component of food as phosphatidylcholine. Consequently, food with more naturally occurring fat such as meat, eggs, dairy and nuts are the richest sources of choline, with produce and grains contributing a lesser amount.

The active form of folate (Vitamin B9) is 5'-methyltetrahydrofolate, which supplies a methyl group to homocysteine to yield methionine and tetrahydrofolate. Once folate has donated its methyl group, it must be remethylated in the folate cycle to be reused. The primary source of these methyl groups is serine. Contrary to popular belief, folate itself is a minor dietary source of methyl groups. Even taking supplements labelled "methyl folate" or "activated folate" or eating green leafy vegetables provides minimal extra methylation substrate. With regards to its role in methylation, folate is better thought of as a carrier molecule analagous to homocysteine rather than as a methyl source.

Most methionine in our diet is found as a component of protein, which requires extensive digestion by a slew of enzymes to release methionine as an amino acid before it can enter the methionine cycle. Vitamin U (S-methylmethionine) is methionine with an extra methyl group, although unlike methionine, Vitamin U is rarely a component of proteins. It supplies a methyl group to homocysteine yielding two molecules of methionine. Vitamin U is abundant in vegetables and fruits, especially cruciferous (e.g. cabbage, kale) and stalky (e.g. celery, asparagus) vegetables.

The degree to which these methyl donors contribute to the methionine cycle is dependent upon our diet. In a diet rich in protein and fats, methionine and choline will be major sources. In a diet in which more calories are gleaned from whole grains, betaine will make a greater contribution. Folate and Vitamin U will make larger contributions in diets rich in fresh produce.

Take care and good luck,