Biological complexity: the vital importance of heme (Introduction)

by David Turell , Wednesday, June 30, 2021, 23:42 (1030 days ago) @ David Turell

It is the starting point for the manufacturer of hemoglobin and more:

https://evolutionnews.org/2021/06/designed-for-a-purpose-heme-production-defeats-evolut...

"Seven scientists (Galvin Leung et al.) from two UK universities (Leicester, Bristol) explain the significance of heme in their paper, “Unravelling the mechanisms controlling heme supply and demand,” published in PNAS. Their homage to heme is unrestrained, as is their appreciation for how the cell handles this toxic molecule.

"Heme is essential for the survival of virtually all living systems and is involved in many fundamental biological processes. It is also implicated as a signaling/regulatory molecule and must be mobilized in response to cellular demands. This presents a complex logistical problem: heme cannot simply diffuse around cells because it is both insoluble and cytotoxic. We show that the cell exhibits exquisite control over release of heme by limiting its availability to one molecule or less within cellular compartments.

"Heme is essential for the survival of virtually all living systems — from bacteria, fungi, and yeast, through plants to animals. The family of heme proteins is vast, and heme proteins are responsible for a multitude of functions that are essential for the survival of the cell. To meet the needs of supply and demand for heme in cells, most organisms need to synthesize it. Biosynthesis of the heme cofactor is, therefore, one of the most important metabolic processes in biology; it occurs as an eight-step enzymatic pathway, the last three steps of which occur in the mitochondria. (my bold)

"It takes eight steps to synthesize one heme molecule, and virtually all life needs it — even bacteria, among the simplest of organisms. The other enzymes that construct heme had to already exist before heme could do its job. This is a serious chicken-and-egg problem for the origin of life. (my bold)

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"We suggest an exchange mechanism between protein partners to control supply and demand. Such a mechanism would provide an in-built buffering capacity for heme, enable cells to hoard supplies of heme, and protect the cell against the undesirable effects of heme.

"How about that; cells know the law of supply and demand. Where did they learn that? In protocell economics class? They also know how to “hoard supplies” of heme (actually, how to maintain emergency stockpiles).

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"A cell cannot maintain a “pool” of heme to draw from, as once thought, because heme is a “nuisance” to cells. It tends form free radicals, which are dangerous, and though hydrophobic, it dimerizes in solution, making it unsuitable for delivery to proteins that only need one heme molecule per binding site.

"A free molecule of heme can therefore only exist transiently, and if a large reserve of heme is present, the heme molecules would presumably need to be exchanged rapidly between binding partners to remain solubilized, in the same way that heme is solubilized within the interior of other well-known heme proteins (e.g., hemoglobin).

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"heme availability…. The results demonstrate that concentrations are typically limited to one molecule or less within cellular compartments. These miniscule amounts of free heme are consistent with a system that sequesters the heme and is able to buffer changes in heme availability while retaining the capability to mobilize heme when and where it is needed. … This exquisite control, in which heme is made available for transfer one molecule at a time, protects the cellagainst the toxic effect of excess heme and offers a simple mechanism for heme-dependent regulation in single-molecule steps.

"In effect, the cell maintains “an exchangeable (buffered) heme reservoir” that solves the availability problem while simultaneously protecting the cell from heme’s toxic effects. Free heme (the risky kind) was detected only in “a minute fraction of the entire amount of heme present in the cell”

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"This exquisite control also provides a mechanism for heme-dependent signaling and regulation, as heme can be supplied discretely, leading to the switching on of proteins in single-molecule steps.

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"To nail the case for design, consider the level of exquisite control...The human body makes around 250 billion red blood cells per day, and each RBC contains 270 million hemoglobin molecules, each constructed with 4 heme groups. That multiplies out to 27 billion trillion hemes per day!

"It’s amazing enough that each cell in the body orchestrates its synthesis and availability of heme. On top of that, the whole body, too, regulates the number of hemoglobin molecules and red blood cells that carry another cytotoxic substance — oxygen — from our lungs to each cell in a safe, regulated, exquisitely controlled manner. Every red-blooded person should take this to heart: we would be walking packages of explosives if it were not for mechanisms “designed for the purpose” of using energy safely for life,..."

Comment: Toxic heme is vital and is tightly controlled as it is a feedstock for many important living processes. Tell me how that happens by chance. There is no answer but a careful designer creating the process: it can only appear in cellular functions with safeguards simultaneously in place. Not to mention eight specific steps orchestrated by giant complex enzymes made up out of thousands of specific amino acids.