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Could we get by with only essential amino acids in food?

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The content of individual specific amino acids in proteins seems to be key to maintaining a healthy metabolism. A change in composition by restricting certain amino acids leads to overeating, but also to greater wasting of energy as heat, so weight gain does not occur . Recent studies in mouse models clearly show that branched-chain (BCAA) and sulfur amino acids (SAA) play an interesting role here. While the mechanism for branched-chain ones is still very unclear, for sulfur amino acids the most likely mechanism of action appears to be sulfhydration of enzymes . For branched-chain acids, I would guess that the mechanism could be transamination to glutamate, which is metabolized in the TCA cycle in two different ways depending on the metabolic state. Either it is further processed via oxaloacetate into glucose, and then everything works normally, or it is processed by reverse run of IDH2 into citrate and then into fat . And that is the essential difference, which however is not describ...

A fatty diet with sugar produces hydrogen sulfide in the intestines—is it good or not?

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This post will once again be dedicated to hydrogen sulfide (H2S). The studies mentioned in previous posts have shown quite clearly how beneficial hydrogen sulfide produced in liver cells by the enzyme CSE can be. It can even be transported further into the whole body through S-sulfhydration of blood albumin . But will this also apply to hydrogen sulfide produced in the large intestine? Let’s take a look at what the authors of a study examining the influence of hydrogen sulfide on intestinal epithelial cell metabolism found. They also studied this in connection with obesity and a diet rich in fats and sugars. The basic idea is that the effect of a diet high in saturated fats on the development of obesity could be either supported or, conversely, blocked by hydrogen sulfide. We first need to clarify the conditions under which this research was conducted. It was done on obese mice, where obesity was induced by a fatty diet high in coconut oil and sugar, together with a low content of pol...

Hydrogen Sulfide – Regulator of Gluconeogenesis, Vascular Health, Liver, Muscles, Adipose Tissue, etc.

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We continue with the effects of hydrogen sulfide on enzyme activity. We have already seen that H₂S affects the S-sulfhydration of sirtuins, i.e., the activity of deacetylases that change the activity of many enzymes by preventing their “decoration” with an acetyl group . In the case of sirtuin modification, for example, this facilitates the “decoration” of some enzymes with ubiquitin, which leads to their removal. Or it increases their activity after the removal of acetyl “decoration,” if that decoration interferes with the enzyme’s function. Even at this level, things are already quite complicated. But that’s not all. S-sulfhydration of certain sites can occur on many proteins, not just on sirtuins! Research shows that H₂S also sulfhydrates the enzyme pyruvate carboxylase (PC) and also the key metabolic switch, the enzyme AMPK. That would explain further phenomena observed both in vitro (in the test tube) and in vivo (in whole organisms) related to changes in hydrogen sulfide levels. ...

Can Hydrogen Sulfide Protect Beta Cells and Heart Cells in Diabetes and Obesity?

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This is a loose continuation of the previous post about the effects of hydrogen sulfide (H₂S) on cellular metabolism . This time, we will look at a study related to diabetes, focused on the protection of insulin-producing cells—meaning the protection of pancreatic beta cells from high blood glucose levels. We will see that hydrogen sulfide activates the deacetylase SIRT2, improves antioxidant protection via GSH, reduces the level of aldehydes formed by oxidation of polyunsaturated fats in a high-glucose environment through activation of the enzyme ALDH2, and thus acts in a way that makes beta cells more resilient and able to survive even in unfavorable conditions. In the figure, we can actually see everything we need to know. If I were to follow up on the post where I showed that amino acid deficiency activates the enzyme SIRT2 and suppresses the formation of new fats , here we can see the mechanism more precisely. ALDA1  is an activator of the enzyme ALDH2, which removes toxic ald...

Hydrogen Sulfide as a Metabolic Repairman?

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In the previous post we saw how the restriction of sulfur-containing amino acids works in a mouse model. Restricting them to one-sixth essentially prevents fat formation and storage, and re-supplementation almost immediately starts to restore fat stores again—very interesting. A similar effect is seen with overall protein restriction in the diet, as we have already noted . I was thinking about possible mechanisms and almost forgot about the post where I commented on a study linking the (in)sufficiency of amino acids, the deacetylase SIRT2, and the effects of fructose—specifically the effect of activation of the enzyme KHK, which phosphorylates fructose . The conclusion of that reasoning was that amino acid deficiency activates SIRT2 and thereby limits fat formation. This manifests itself through deacetylation and removal of the enzyme ACSS2, which activates acetate into acetyl-CoA—thus reducing the production of substrates for new fat synthesis. But fructose, via KHK, suppresses SIRT2...

Do We Get Fat from BCAAs or SAAs? Or from Ammonia?

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In my previous post I showed results of studies on diets restricting certain specific amino acids. Overall, that “divine” construction kit consists of twenty amino acids, twenty building blocks. Some are straight sections, some are bent, some pieces allow flexibility, some allow branching—just like a classic children’s building toy. In the last post we talked about branched-chain amino acids (BCAAs). It seems that restricting them leads to weight loss in mice, but there are still some “bugs.” For example, it doesn’t work in female mice. Females are simply more resistant, and we basically don’t know what is happening in the body. I suggested the idea that since females inherently have a higher percentage of body fat, their fat tissue is more resistant to overload, e.g., when overeating. And BCAA restriction in mice is actually connected with increased food intake. So my conclusion is that the positive results in males are caused by activation of cellular senescence and insulin resistan...

Restricting Protein or Certain Amino Acids Helps Burn Fat

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Recently, many social media influencers have been focusing on studies that surprisingly show how limiting protein in the diet leads to increased calorie burning, usually compensated by higher carbohydrate or fat intake. This is a very interesting area of research, with many unanswered questions.   The most frequently cited study was conducted on young, lean men. The results were highly surprising, hence the attention.   FGF21 is the primary factor behind the positive effects of restricting protein to around 9% of calories To maintain the same weight, caloric intake had to be significantly increased. This is related to energy expenditure through thermogenesis.  LPHC: Low-protein, high-carb diet; LPHF: Low-protein, high-fat diet;  HPD: Diet with standard protein content Is this practically applicable? Does it carry any risks? These questions still need to be answered. We don’t know. But we have other studies. For example, a recent study linked protein or bran...