Low amounts of the essential amino acid methionine diet help form new blood vessels

Putting mice on a diet containing low amounts of the essential amino acid methionine triggered the formation of new blood vessels in skeletal muscle, according to a new study from Harvard T.H. Chan School of Public Health. The finding adds insight to previous research showing that a methionine-restricted diet extends lifespan and healthspan, suggesting that improved vascular function may contribute to these benefits.

Previous work by Mitchell and colleagues has shown that a methionine-restricted diet increases production of the gas, hydrogen sulfide. This smelly molecule gives rotten eggs their characteristic odor, but is also made in our cells where it functions in myriad beneficial ways. One of these is to promote the growth of new blood vessels from endothelial cells—a process known as angiogenesis.

Lack of oxygen, or hypoxia, is the best-characterized trigger of angiogenesis. Hypoxia occurs in tissues when a vessel is blocked, or upon acute exercise when oxygen delivery is limited. However, methionine restriction triggered angiogenesis despite normal oxygen delivery, suggesting involvement of a pathway sensing amino acid deprivation rather than hypoxia.

The smell — that’s from hydrogen sulfide, which is produced when sulfur-rich food is digested by bacteria in your colon. Foods that promote sulfur smells include eggs, meat, fish, beer, beans, broccoli, cauliflower and cabbage.

In an accompanying paper from David Sinclair’s group at Harvard Medical School published in the same issue of Cell, the authors found that treatment with NMN—a small molecule activator of the longevity-associated protein SIRT1—either alone or in combination with hydrogen sulfide (in the form of NaHS), increased vascular density in the skeletal muscle of elderly mice and boosted the aging animals’ exercise capacity.

Methionine, cysteine, homocysteine, and taurine are the 4 common sulfur-containing amino acids, but only the first 2 are incorporated into proteins. Sulfur belongs to the same group in the periodic table as oxygen but is much less electronegative. This difference accounts for some of the distinctive properties of the sulfur-containing amino acids. Methionine is the initiating amino acid in the synthesis of virtually all eukaryotic proteins; N-formylmethionine serves the same function in prokaryotes. Within proteins, many of the methionine residues are buried in the hydrophobic core, but some, which are exposed, are susceptible to oxidative damage. Cysteine, by virtue of its ability to form disulfide bonds, plays a crucial role in protein structure and in protein-folding pathways. Methionine metabolism begins with its activation to S-adenosylmethionine. This is a cofactor of extraordinary versatility, playing roles in methyl group transfer, 5′-deoxyadenosyl group transfer, polyamine synthesis, ethylene synthesis in plants, and many others. In animals, the great bulk of S-adenosylmethionine is used in methylation reactions. S-Adenosylhomocysteine, which is a product of these methyltransferases, gives rise to homocysteine. Homocysteine may be remethylated to methionine or converted to cysteine by the transsulfuration pathway. Methionine may also be metabolized by a transamination pathway. This pathway, which is significant only at high methionine concentrations, produces a number of toxic endproducts. Cysteine may be converted to such important products as glutathione and taurine. Taurine is present in many tissues at higher concentrations than any of the other amino acids. It is an essential nutrient for cats.

High levels of methionine can be found in eggs, meat, and fish; sesame seeds, Brazil nuts, and some other plant seeds; and cereal grains.

Cysteine, a sulfur-containing amino acid, plays an important role in a variety of cellular functions such as protein biosynthesis, methylation, and polyamine and glutathione syntheses. In trypanosomatids, glutathione is conjugated with spermidine to form the specific antioxidant thiol trypanothione (T[SH]2) that plays a central role in maintaining intracellular redox homeostasis and providing defence against oxidative stress.


Protozoan parasites in humans

Three protozoan parasites of humans, Entamoeba histolytica, Giardia intestinalis, and Trichomonas vaginalis, share various biological and biochemical characteristics, including anaerobic carbohydrate metabolism and the lack of typical mitochondria
(“amitochondriate”). The ATP generation in these parasites occurs exclusively through substrate-level phosphorylation, despite differences in their life cycles and pathogenic properties.

As obligatory parasites, these organisms have a reduced ability for the de novo (anew) synthesis of essential building blocks of DNA and proteins, including nucleic acid precursors and amino acids. As a consequence, certain metabolic pathways either are missing in these organisms or are divergent from those of mitochondriate organisms. Sulfur-containing-amino-acid metabolism represents one such divergent metabolic pathway in these three “amitochondriate” protists.

Essential Sulfur-containing amino acids

Sulfur-containing amino acids are essential for a variety of biological activities, including protein synthesis, methylation, polyamine synthesis, coenzyme A production, cysteamine production, taurine production, iron-sulfur cluster (ISC) biosynthesis, and antioxidative stress defense.

Source:  https://www.hsph.harvard.edu/news/press-releases/sulfur-amino-acid-restriction-diet-blood-vessel-formation/


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