Biochemical controls: the kidney (Introduction)

by David Turell @, Monday, April 25, 2022, 20:47 (65 days ago)

The kidney does manythings at once to produce proper urine:

https://medicalxpress.com/news/2022-04-key-urinary-kidney.html

"Proper function of the kidney is critical for concentrating urine, regulating blood pressure, and for the tight control of electrolyte levels in the blood. The kidney achieves these important functions through many microscopic functional units, called nephrons. These nephrons consist of different segments with distinct functions. How these segments form during development and how their function is maintained in the adult is only partially understood.

***

"The distal nephron is particularly important for the ability of the kidney to concentrate urine, regulate blood pressure, and control calcium and magnesium blood levels. Parts of the distal nephron have specific salt transporters, which are the main targets of medicine's most effective diuretics, used in the treatment of hypertension and chronic kidney disease. Thus, understanding how their function is regulated has important implications for these common diseases.

***

"Previously, Marneros showed in work published in Developmental Cell in 2020 that AP-2β is required for the formation of the segment of the distal nephron that is targeted by thiazide diuretics: the distal convoluted tubule. This prompted him to ask whether the closely related protein AP-2α also has a function in the kidney. His team found that while AP-2β function in the kidney is required for survival by regulating the development and function of distal convoluted tubules, AP-2α is important for the proper function of a different segment of the distal nephron, called the collecting duct, which is involved in the kidney's ability to concentrate urine. Notably, loss of even only half of AP-2β levels causes progressive kidney disease, whereas complete loss of AP-2α resulted in less severe kidney abnormalities.

"'These findings show that AP-2α and AP-2β are important regulators of distinct segments of the distal nephron. These new observations in genetic mouse models are important contributions to our understanding of how specific segments of the kidney are regulated on a molecular level," says Marneros."

Comment: As in all these situations, everything must work together from the start, or it won't work. That is irreducible complexity as must be fully designed from the start to work properly. Mutating it bit by bit is impossible. This intact functkon had to first appear in the Cambrian explosion.

Biochemical controls: how enzymes work

by David Turell @, Monday, April 25, 2022, 21:08 (65 days ago) @ David Turell

Picking their activity apart:

https://www.sciencedaily.com/releases/2022/04/220425104932.htm

"This concept is known as "electrostatic stress." For example, if the substrate (the substance upon which the enzyme acts) carries a negative charge, the enzyme could use a negative charge to "stress" the substrate and thus facilitate the reaction. However, a new study by the University of Göttingen and the Max Planck Institute for Multidisciplinary Sciences in Göttingen has now shown that, contrary to expectations, two equal charges do not necessarily lead to repulsion, but can cause attraction in enzymes. The results were published in the journal Nature Catalysis.

"The team investigated a well-known enzyme that has been studied extensively and is a textbook example of enzyme catalysis. Without the enzyme, the reaction is extremely slow: in fact, it would take 78 million years for half of the substrate to react. The enzyme accelerates this reaction by 1017 times, simply by positioning negative and positive charges in the active centre. Since the substrate contains a negatively charged group that is split off as carbon dioxide, it was assumed for decades that the negative charges of the enzyme serve to stress the substrate, which is also negatively charged, and accelerate the reaction. However, this hypothetical mechanism remained unproven because the structure of the reaction was too fast to be observed. (my bold)

***

"Unexpectedly, the negative charges of enzyme and substrate did not repel each other. Instead, they shared a proton, which acted like a kind of molecular glue in an attractive interaction. "The question of whether two equal charges are friends or foes in the context of enzyme catalysis has long been controversial in our field, and our study shows that the basic principles of how enzymes work are still a long way from being understood," says Tittmann. The crystallographic structures were analysed by quantum chemist Professor Ricardo Mata and his team from Göttingen University's Institute of Physical Chemistry. "The additional proton, which has a positive charge, between the two negative charges is not only used to attract the molecule involved in the reaction, but it triggers a cascade of proton transfer reactions that further accelerate the reaction," Mata explains.

"'We believe that these newly described principles of enzyme catalysis will help in the development of new chemical catalysts," says Tittmann. "Since the enzyme we studied releases carbon dioxide, the most important greenhouse gas produced by human activities, our results could help develop new chemical strategies for carbon dioxide fixation.'"

Comment: this shows how enzymes work, as if they knock two heads together, and demand cooperation. Enzymes force reactions to occur at the high-speed life's biology requires. Each giant enzyme molecule is precisely designed for each reaction it speeds up. Organic chemistry uses molecules that won't react quickly by themselves. Unfortunate, but those molecules are the only ones that will work. God knows what He is doing even if dhw has doubts with his second-guessing. It seems agnostics know better than God how to do things.

Biochemical controls: the kidney pumps blood

by David Turell @, Wednesday, May 18, 2022, 15:24 (42 days ago) @ David Turell

The kidney doesn't just filter blood, it pumps it along:

https://medicalxpress.com/news/2022-05-reveals-kidney-cells-dont-filter.html

"Human kidneys are an intricate network of tubes that process roughly 190 quarts of blood every day. Lining these tubes are epithelial cells that transport blood through the kidneys and circulate it back into the body. How these immobile cells generate the mechanical force needed to do their job is not fully understood. To unlock the secrets of this fluid transport process, a Johns Hopkins mechanical engineer has created a device that measures mechanical forces generated by both healthy and diseased kidney cells.


"'Fundamental physical laws say that you need forces to move things. In this case, the cells are not moving, but they are moving fluid. The question then becomes how do they do this?" said Sean Sun, a professor in the Whiting School of Engineering's Department of Mechanical Engineering and a core member of the Institute for NanoBioTechnology.

***

"The researchers noticed that kidney epithelial cells behave like mechanical fluid pumps and actively generate a fluid pressure gradient. The fluid pumping behavior is characterized by a pump performance curve, which is very much like a water pump in a house. Most people believe that kidneys behave like a conventional filter, which needs external pressure to move fluid. However, Sun and his team showed that cells can actually generate the needed pressure themselves—an insight with important implications for understanding kidney physiological function.

"'Everyone hears that kidneys filter blood, but conceptually that is incorrect. What we showed is that kidney cells are pumps, not filters, and they are generating forces," Sun said."

Comment: kidney blood vessels are extremely tiny, and the arterial blood delivered to them under pressure must be reduced to almost zero for proper filtration. That an extra push is designed into kidney cells is not surprising, but is necessary. Such complexity is irreducibly complex as it must be designed all at once for the kidney system to work.

Biochemical controls: controlling cell protein output

by David Turell @, Tuesday, May 31, 2022, 19:20 (29 days ago) @ David Turell

The body has control systems that drive production and slow production in a tight fashion:

https://phys.org/news/2022-05-decoding-protein-cells-healthy.html

"Cells produce proteins like little factories. But if they make too much at the wrong times it can lead to diseases like cancer, so they control production with a process called RNA interference (RNAi).

***

"They [a research group] recently discovered how RNAi's workhorse protein Argonaute (Ago) leverages limited resources to keep protein production on track.

"It's important to understand exactly how RNAi works because it's such a basic and heavily used process, Joshua-Tor said. It also offers a kind of safety net for therapeutics because it doesn't make permanent changes to cells and can be reversed.

***

"Ago helps cut off protein production by finding, binding, and destroying molecules called mRNA—which tell cells to make proteins. But the amount of Ago in the body pales in comparison to the amount of mRNA it must target. After destroying one MRNA molecule, the protein is still capable of finding another but it can't move on without help. Bibel discovered how cells use a process called phosphorylation to break Ago's grip on a mRNA target, allowing it to commute to the next.

"Bibel explains that their "theory is that having phosphorylation promote release is a way that you could free up Argonaute because when the target gets released, the guide's still there and it's super duper stable. So our thinking is that by phosphorylating it, you're going to free it to go repress other targets—because it's still totally capable of doing that work.'"

Comment: more evidence of purposeful design. Controlling production rates is vital, so start and stop controls must be designed together all at once.

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