What influences cognition? The exchange in purine bases and amino acids in the brain.

Photo: Adenine structure, one of the purine bases, specifically connects to thymine via hydrogen bonding in DNA and uracyl in RNA, as discovered by James Watson and Francis Crick in the 50s. Credit:kropekk_pl

Of the about 20,000 metabolites discovered so far in human blood serum, over 1,300 and 140 lipids have been observed to profile the brain’s uptake and release.

A new study led by Chinese scientists, published in the journal ,,Neuron,” explains why the human brain, which accounts for only 2% of body weight, consumes nearly 20% of the body’s glucose and oxygen resources. In simpler terms, neuronal activity requires these fuels, along with amino acids and lipids, to develop and maintain proper functions. The scientists observed differences in the quantities of the studied substances among individuals from whom blood samples were taken for testing. However, they noted that the participants were under anesthesia during the study, which could have influenced the results. This impact is believed to affect the functioning of the brain more than the abundance of the critical compounds themselves.

How do we use energy?

What’s fascinating, the observed differences in byproducts between participants were seen as greater than those between the brain and leg blood ingredients, although in the case of leg blood vessels, over 1,500 compounds circulate. The differences in vessel size are likely to be clear; for instance, the femoral artery is one of the largest arteries in the human body, while the blood vessels in the brain are much smaller. Moreover, it is already established that the brain consumes glucose at a rate exceeding 10%, according to comparisons of arteriovenous glucose levels. A key method for studying tissue metabolism involves measuring the quantities of substances across different tissues. Recent advancements in metabolomics, the study of organic compounds either produced within the body or obtained from external sources, have enabled the application of arteriovenous metabolomics in selected species. This has allowed for the quantification of metabolite exchanges that are specific to different organs or tissues. As a result, this approach has provided valuable insights into how, for example, the human heart utilizes energy. Is it now time to focus on the brain?

We observed a high net uptake of glucose, taurine, and hypoxanthine and identified glutamine and pyruvate as significantly released metabolites by the brain,

say Yilong Wang and Woo-ping Ge of Chinese Institute for Brain Research in Beijing.

Out of the 5,384 compounds analyzed, 738 (13.7% of all measured features) were taken up by the brain, while 627 (11.6%) were released from the brain. The remaining 74.7% of the compounds showed no significant difference in values between arterial and venous plasma samples, indicating they remained stable – write scientists.

What is contained within neuronal tissue?

 The brain utilizes both purines and amino acid derivatives in varying amounts, along with various released byproducts. Some of these byproducts are not yet fully classified in terms of their biological properties. Nevertheless, the research suggests that at least one of these substances is absorbed at a net rate of about 26% into the brain’s structural tissue. The predictive formula for this substance, along with its structure, suggests the presence of hydrogen, carbon, and oxygen forming bonds with boron, which in turn binds with sulfur. Is this essential for brain plasticity and, consequently, overall health? As the scientists claim, some compounds are absorbed or released more during youth, while others remain stable in adulthood even when their uptake occurred earlier in life. Around 50 of these compounds maintain remarkable stability during the 40s, despite having been released earlier. Additionally, no compound was found to be absorbed more by the human brain in the ≥40 age group compared to its absorption in the 20s age group. However, according to the study, with age, the brain consumes less glucose, taurine, and 3MGA, while releasing more asparagine, biliverdin, choline, trimethylamine, and caprylate. At the same time, scientists indicated the importance of the liver and its vessel’s role in absorbing substances necessary for the brain from the blood.

,, The arteriovenous data presented in this study were collected from human subjects who were under anesthesia and had fasted overnight to closely approximate resting state. Given this fasting condition, there is a potential increase in lipid utilization and a decrease in carbohydrate utilization. However, it is important to recognize that the effects of anesthesia and fasting on brain metabolic exchange can be unpredictable. Therefore, caution should be exercised when concluding about all metabolites,” – scientists claim. 


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