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Homeostasis: Life’s balancing act as a challenge to unguided evolution


From Biologic Institute’s Ann Gauger, on J. Scott Turner’s forthcoming Purpose and Desire: at Evolution News & Views:

Claude Bernard (1813-1878) was a French physiologist, one of the most famous scientists of his age, so famous that he appeared in poems, novels, and memoirs of the period both in France and abroad. Think Albert Einstein.

Now, however, he is most famous for his idea that the miliéu interieur, or internal environment of living things, must remain constant to sustain and maintain life. This idea is given the name homeostasis, defined as a “self-regulating process by which biological systems tend to maintain stability while adjusting to conditions that are optimal for survival. If homeostasis is successful, life continues; if unsuccessful, disaster or death ensues.”

Here’s the point. Can any neo-Darwinian process account for the existence of homeostasis? I have indicated just some of the kinds of things that must be regulated, each with its own controls. So as an example of the complex regulation required to maintain just one element, listen to this ID the Future podcast by physician Howard Glicksman. Calcium is regulated by the parathyroid gland using an intricate set of interacting systems of calcium uptake and release, primarily from the bone, but also the gut and the kidneys. And strict regulation of calcium concentration is essential for life. More.

Darwinism can do anything, Ann. Anything, everything, and nothing.

Turner is lucky he is allowed to openly wonder about that as much as he does.

Seriously, the principle difference between life and non-life is that life forms engage in strenuous and very complex efforts to remain in a highly organized state. Non-life forms do not make such efforts. Little progress will be made understanding origin of life, for example, if we do not even wish to consider that but instead propose scenarios by which life just happens. The way rocks just fall.

See also: J. Scott Turner in the Chronicle of Higher Education — ID is asking the right questions! (2007)


A biologist’s deep wish for Darwinism to make sense

Regulation of Potassium Homeostasis 1 http://reasonandscience.heavenforum.org/t2457-regulation-of-potassium-homeostasis Potassium is the most abundant cation in the intracellular fluid, and maintaining the proper distribution of potassium across the cell membrane is critical for normal cell function. Potassium plays a key role in maintaining cell function. Almost all cells possess an Na+-K+-ATPase, which pumps Na+ ( Sodium ) out of the cell and K+ ( Potassium ) into the cell and leads to a K+ gradient across the cell membrane (K+in>K+out) that is partially responsible for maintaining the potential difference across the membrane. This potential difference is critical to the function of cells, particularly in excitable tissues, such as nerve and muscle. The body has developed numerous mechanisms for defense of serum K+. These mechanisms serve to maintain a proper distribution of K+ within the body as well as regulate the total body K+ content. Otangelo Grasso
Iron Uptake and Homeostasis in Cells 1 http://reasonandscience.heavenforum.org/t2443-iron-uptake-and-homeostasis-in-prokaryotic-microorganisms The origin of life required two processes that dominated: (1) the generation of a proton gradient and (2) linking this gradient to ATP production in part and in part to uptake of essential chemicals and rejection of others. The generation of a proton gradient required especially appropriate amounts of iron (Fe2+), levels for electron transfer and the ATP production depended on controlling H+, Mg2+ and phosphate in the cytoplasm. 8 Iron serves essential functions in both prokaryotes and eukaryotes, and cells have highly specialized mechanisms for acquiring and handling this metal. 2 Organisms use a variety of transition metals as catalytic centers in proteins, including iron, copper, manganese, and zinc. Iron is well suited to redox reactions due to its capability to act as both an electron donor and acceptor. In eukaryotic cells, iron is a cofactor for a wide variety of metalloproteins involved in energy metabolism, oxygen binding, DNA biosynthesis and repair, synthesis of biopolymers, cofactors, and vitamins, drug metabolism, antioxidant function, and many others. Because iron is so important for survival, organisms utilize several techniques to optimize uptake and storage to ensure maintenance of sufficient levels for cellular requirements. However, the redox properties of iron also make it extremely toxic if cells have excessive amounts. Free iron can catalyze the formation of reactive oxygen species such as the hydroxyl radical, which in turn can damage proteins, lipids, membranes, and DNA. Cells must maintain a delicate balance between iron deficiency and iron overload that involves coordinated control at the transcriptional, post-transcriptional, and post-translational levels to help fine tune iron utilization and iron trafficking. 4 Question: Had this coordination not have to be fully setup right when cells first became alive ? Otangelo Grasso
Homeostasis in cells, and origin of life scenarios http://reasonandscience.heavenforum.org/t2447-homeostasis-in-cells-and-origin-of-life-scenarios One of the key properties of life is Regulation, including homeostasis. Freeman Dyson, Origins of Life, page 73: The essential characteristic of living cells is homeostasis, the ability to maintain a steady and more-or-less constant chemical balance in a changing environment. Homeostasis is the machinery of chemical controls and feedback cycles that make sure that each molecular species in a cell is produced in the right proportion, not too much and not too little. Without homeostasis, there can be no ordered metabolism and no quasi-stationary equilibrium deserving the name of life. The question Why is life so complicated? means, in this context, Given that a population of molecules is able to maintain itself in homeostatic equilibrium at a steady level of metabolism, how many different molecular species must the population contain? From the fact that bacteria have generally refused to shrink below a certain level of complexity, we may deduce that this level is in some sense an irreducible minimum. I am conjecturing that the minimum population size required for homeostasis would be ten or twenty thousand monomer units. And more important, I am suggesting that the most promising road to an understanding of the origin of life would be to do experiments like the Spiegelman and Eigen experiments but this time concerned with homeostasis rather than with replication. The essence of life from the beginning was homeostasis based on a complicated web of molecular structures. Life by its very nature is resistant to simplification, whether on the level of single cells or ecological systems or human societies. Life could tolerate a precisely replicating molecular apparatus only by incorporating it into a translation system that allowed the complexity of the molecular web to be expressed in the form of software. After the transfer of complication from hardware to software, life continued to be a complicated interlocking web in which the replicators were only one component. The replicators were never as firmly in control as Dawkins imagined. In my version the history of life is counterpoint music, a two-part invention with two voices, the voice of the replicators attempting to impose their selfish purposes upon the whole network and the voice of homeostasis tending to maximize diversity of structure and flexibility of function. The tyranny of the replicators was always mitigated by the more ancient cooperative structure of homeostasis that was inherent in every organism. Homeostasis is the mechanistic fundament of biology, beginning with the protocell 1 Two fundamental properties of life as we recognize it are homeostasis and redox chemistry. Redox homeostasis is defined here as the maintenance of a constant electrochemical potential and ionic concentration gradient across a cellular boundary, despite fluctuations in the electrochemical potential of the external environment and despite changing identities and activities of electron donors and acceptors. 2 The transition to free-living cells depends on the proto-cells’ ability to maintain a proton motive force for energy conversion, providing for metabolism, for active transport, and for synthesis of informational and structural macromolecules. A feature that distinguishes living from non-living matter is homeostasis – the maintenance of a constant internal environment despite changes in the external environment. A second feature of all known life is that living things are composed of spatial compartments, called cells. Cellular homeostasis requires a system of integrated feedback and feedforward, producing adaptive responses to, and anticipation of, ultimately uncontrollable changes in the properties of the outside world. I have been trying to imagine a framework for the origin of life, guided by a personal philosophy that considers the primal characteristics of life to be homeostasis rather than replication, diversity rather than uniformity, the flexibility of the genome rather than the tyranny of the gene, the error tolerance of the whole rather than the precision of the parts. A Massachusetts General Hospital (MGH) research team investigating how the earliest stages of life might have developed has discovered a way the first living cells could have met a key challenge -- maintaining a constant internal environment, a process called homeostasis, even when external conditions change. "Modern cells are constantly regulating what they are doing -- synthesizing, degrading and exporting a whole suite of RNAs and proteins -- depending on the cell's particular needs at the time," says Aaron Engelhart, PhD, of the MGH Department of Molecular Biology and the Center for Computational and Integrative Biology, lead author of the paper. "One would expect that the earliest cells weren't nearly as complex as today's cells, but they still had the need to regulate their internal environment. 1 Otangelo Grasso
Otangelo Grasso @1 and gpuccio @2, Very insightful comments. Thanks. Dionisio
Many years ago now, a young nurse suspected something was causing or contributing to post-parturition depression in her ward. It was intuition and observation that led her. But when she proposed it she was hammered as in those days calcium was just an inert non-reactive ingredient the only role of which was bone construction. If either of you gentlemen could contribute it would settle me, because I thought her theory had some merit. If it is wrong or right it is immaterial to me now, but it would put an end to my wondering. Belfast
A lovable rascal. :) Mung
Mung: "Are you actually trying to confuse rvb8?" What a rascal I am! :) gpuccio
1) The ability to generate and maintain structures and systems that require an extremely tight control of energy management, because of their low entropy and high information and order.
Are you actually trying to confuse rvb8? Mung
Otangelo Grasso: Very, very good thoughts. Thank you indeed. "Controlled environment is the essence of life. This cellular separation from the surround pretty much builds around a simple and effective principle of divide et impera, i.e., divide the world into external environment and internal space and govern everything which goes into or out of the living cell/organism. Ca2+ permits binding reactions that are ~ 100 times faster than Mg2+( magnesium )." Absolutely true! A couple of times, in the past, I have tried to suggest three basic components that IMO are absolutely needed for any form of life to exist. They are, more or less: 1) The ability to generate and maintain structures and systems that require an extremely tight control of energy management, because of their low entropy and high information and order. 2) The ability to generate and maintain far from equilibrium systems as a general context in the cell. 3) The ability to generate a partition between the outer and the inner, by specific membranes and membrane functions. So, it seems that we absolutely agree on the third point! Moreover, while you appropriately focus on the regulation of intracellular calcium, the separation between outer and inner obviously includes many other aspects, like Na and K regulation, and so on. Also, the plasma membrane is probably the greatest signal transducer in living beings, with its many specific receptors and corresponding intracellular cascades that transmit the signals to the nucleus. Indeed, most informational signalings stop at the membrane, and are translated and transmitted to the inner part of the cell. "This is a interdependent system !" You bet! There are tons of functional complexity in each of its components, of course, and tons of irreducible complexity in the system as a whole. But I am sure that our design-denier friends will see no difficulty in imagining that they can imagine an explanation for all that! :) gpuccio
How intracellular Calcium signaling, gradient and its role as a universal intracellular regulator points to design http://reasonandscience.heavenforum.org/t2448-howintracellular-calcium-signaling-gradient-and-its-role-as-a-universal-intracellular-regulator-points-to-design In view of the importance of calcium (Ca2+) as a universal intracellular regulator, its essential role in cell signaling and communication in many biological intra and extra cellular processes, it is surprising how little it is mentioned in the origins ( evolution/ID) debate. Most discussions about the origin of life start with RNA worlds versus metabolism first scenarios, panspermia, hydrothermal vent theory etc. The origin of life cannot be elucidated, without taking into consideration and explaining how the calcium signaling machinery and cell homeostasis appeared. The Calcium gradient : The ability of cells to maintain a large gradient of calcium across their outer membrane is universal. All biological cells have a low cytosolic (liquid found inside Cells ) calcium concentration, can and must keep this even when the free calcium outside is up to 20,000 times higher concentrated! The first forms of life required an effective Ca2+ homeostatic system, which maintained intracellular Ca2+ at comfortably low concentrations—somewhere around 100 nanomolar, this being ?10,000–20,000 times lower than that in the extracellular milieu. Damage the ability of the plasma membrane to maintain this gradient and calcium will flood into the cell, precipitating calcium phosphate, damaging the ATP-generating machinery, and kill the cell. At millimolar concentrations, calcium competes with Mg2+ ( magnesium), binds to DNA and RNA, and clogs it up. Ca2+ binds to nucleotides, so they do not work properly. And crucially Ca2+, at too high concentrations, precipitates carbonate, phosphate, and sulfate. So if a primeval cell was to work, it had to get rid of Ca2+, lowering it at least to submillimolar levels, if not submicromolar. In fact, without control of intracellular Ca2+, life would never have got off the ground! Control of intracellular Ca2+ had to be a crucial step in allowing the original cells to survive and replicate, even before RNA or DNA synthesis could begin in earnest. The evidence we have from molecular biology, together with the toxic nature of prolonged high Ca2+ levels inside cells, argues strongly that primeval cells must have had Ca2+ pumps to keep their free intracellular Ca2+ low, setting the scene for the ‘calcium pressure’ across then plasma membrane to be exploited to act as the source for cell activation. In order to maintain such a low cytosolic calcium concentration, Ca2+ ions thus have to be transported against a steep concentration gradient. In addition, the positively charged molecules are often transported against a very negative membrane potential, contributing to a large electrochemical gradient for Ca2+ ions. The concentration is tightly regulated by Ca 2+ -binding proteins, Ca 2+ pumps and other transporters. This gradient has to be maintained by the continuous exclusion of Ca2+ from the cell. The removal of Ca2+ by active extrusion requires energy to pump the Ca2+ against the electrochemical gradient. The metabolic apparatus that serves this function involves Ca2+ protein-based and non-proteinaceous channels, Ca2+ antiporters (Ca2+/2H+, Ca2+/Na+), and ATP-dependent Ca2+ pumps. The making of a power gradient ( which is a thermodynamically uphill process ) is always an engineering achievement, and a lot of knowledge, planning, and intelligence is required for setup. Hydroelectric dams are highly complex, and always the result of years of planning by the most skilled, educated and knowledge engineers of large companies. As for many human inventions, the engineering solutions discovered by man are employed in nature at least since life began in a far more elaborate and sophisticated way. So inanimate chemistry had the innate drive of trials and errors to produce a cell membrane, and amongst tons of other things, a Ca+ gradient through highly complex Calcium channels to keep a 10 000-fold higher concentration of calcium outside the cell than inside the cytosol in order to create a environment suited for a protocell to keep its vital functions and not to die ? Why would chemical elements do that? Did they have the innate drive and goal to become alive and keep an ambiance prerequisite, homeostasis of various elements, to permit life ? Calcium signaling: Metabolism of ATP required intracellular free Ca(2+) to be set at exceedingly low concentrations, which in turn provided the background for the role of Ca(2+) as a universal signalling molecule. Furthermore, Ca(2+) is a universal carrier of biological information, and one of the most extensively employed signal transduction mechanisms: it controls cell life from its origin at fertilization to its end in the process of programmed cell death. Ca(2+) is a conventional diffusible messenger released inside cells by the interaction of first messengers with plasma membrane receptors. Perhaps the most distinctive property of the Ca(2+) signal is its ambivalence: while essential to the correct functioning of cells, Ca(2+) becomes an agent that mediates cell distress, or even (toxic) cell death, if its concentration and movements inside cells are not carefully tuned. A prolonged high level of intracellular free Ca2+ irreversibly damages mitochondria and can cause chromatin condensation, precipitation of phosphate and protein and activation of degradative enzymes such as proteases, nucleases and phospholipases Calcium ions (Ca2+) serve as a universal signal to modulate almost every aspect of cellular function in all cells. Cells in the three domains of life all have a number of universalities, including intracellular Ca2+. Calcium carries messages to virtually all important functions of cells. Ca2+ signaling pathway plays a key messenger role in regulating many cellular processes including fertilization, contraction, exocytosis, transcription, apoptosis, and learning and memory. Ca 2+ controls the most important cell functions in all eukaryotic organisms. Fertilization, muscle contraction, secretion, several phases of metabolism, gene transcription, apoptotic death, etc. are finely orchestrated by the functional versatility of Ca 2+ signaling and its exquisite spatial and temporal regulation. Most likely its unique coordination chemistry has been a decisive factor as it makes its binding by complex molecules particularly easy, even in the presence of large excesses of other cations, e.g. magnesium. Its free concentration within cells can thus be maintained at the very low levels demanded by the signaling function. A large cadre of proteins exists to bind or transport calcium. They all contribute to buffer it within cells, but a number of them also decode its message for the benefit of the target. The most important of these "calcium sensors" are the EF-hand proteins. Given the central role of intracellular calcium signaling in the living world, a better understanding of the constitution of this calcium-signaling toolkit, and the proteins that comprise it, is crucial to our global understanding of what was required for cells to emerge. These scientific studies highlight the high conservation of the calcium toolkit from prokaryotes to metazoa and the increasing complexity of the proteins that make it up. The necessity of exporting Ca2+ from cells is a direct consequence of the ambivalent nature of the Ca2+ signal. Ca2+ is essential to cells: it presides over the origin of new life at fertilization and assists cells when their vital cycle has come to an end. Between origin and end, however, Ca2+ guides cells in most of what they must do to fulfill the tasks assigned to them. The balance of Ca2+ between cells and the outside ambient must be regulated with utmost precision: any escape that would somehow alter the balance by letting internal Ca2+ increase over the optimal level spells doom for cells. Controlled environment is the essence of life. This cellular separation from the surround pretty much builds around a simple and effective principle of divide et impera, i.e., divide the world into external environment and internal space and govern everything which goes into or out of the living cell/organism. Ca2+ permits binding reactions that are ~ 100 times faster than Mg2+( magnesium ). The maintenance of the stability of cells, osmotic, electrical and chemical, is life essential, and requires the cell to reject certain elements as ions, namely Na+ ( Sodium ), Ca2+ ( Calcium ) and cl ( Chlorine ), while retaining K+ ( potassium ions ) and Mg2+ ( magnesium ) . The levels of these simple ions are related to the cell's activities, both to metabolism and to the functioning of DNA. This requirement to reject Ca2+ in the initial stages of life is the pre-requisite of all its advanced functions. To maintain steady states of flow, cells have numerous signaling (circuit) systems employing carriers and messengers, amongst which co-enzymes are of major importance. To describe cellular homeostasis , in total about twenty elements need to be regulated. To get this is already a major feat. How did inanimated matter achieve this without guiding intelligence ? Inseparable tandem: evolution chooses ATP and Ca2+ to control life, death and cellular signalling. From the very dawn of biological evolution, ATP was selected as a multipurpose energy-storing molecule. Had a adequate energy supply in the cell not to be established prior when life began ? And so, had the origin of energy supply not have to be setup without having evolution at hand as driving force, since dna replication was not setup yet ? Yet, low Ca2+ concentration in the cell is a prerequisite for ATP metabolism. That creates one more remarkable catch22 situation, since for a Ca2+ gradient, membrane channels are required, which are only made using ATP as energy source for its biosynthesis. But the production of ATP requires a existing calcium gradient !! The proposed naturalistic explanations, like Donnan potential without requiring Ca 2+ -ATPases and antiporters are fantasious at best. ATP effects are mediated by an extended family of purinoceptors often linked to Ca(2+) signalling. Similar to atmospheric oxygen, Ca(2+) must have been reverted from a deleterious agent to a most useful (Intra- and extracellular) signaling molecule. Invention of intracellular trafficking further increased the role for Ca(2+) homeostasis that became critical for regulation of cell survival and cell death. Several mutually interdependent effects of Ca(2+) and ATP have been exploited in evolution, thus turning an originally unholy alliance into a fascinating success story. The Regulation of a Cell’s Ca 2+ Signaling Toolkit: The Ca 2+ Homeostasome The Ca 2+ ion serves as a ubiquitous second messenger in eukaryotic cells and changes in the intracellular Ca 2+ concentration regulate many responses within a cell, but also communication between cells. In order to make use of such an apparently simple signal, i.e. a change in the intracellular Ca 2+ concentration, cells are equipped with sophisticated machinery to precisely regulate the shape (amplitude, duration) of Ca 2+ signals in a localization-specific manner. To ascertain such a precise regulation, cells rely on the components of the Ca 2+ signaling toolkit. This embraces Ca 2+ entry systems including Ca 2+ channels in the plasma membrane and organellar membranes, and Ca 2+ extrusion/uptake systems including Ca 2+ -ATPases (Ca 2+ pumps) and Na + /Ca 2+ exchangers. The Ca 2+ -signaling components orchestrate their activity as to ascertain the high accuracy of intracellular Ca 2+ signaling. The total of the molecules that build the network of Ca 2+ signaling components, and that are involved in their own regulation as to maintain physiological Ca 2+ homeostasis resulting in phenotypic stability is named the Ca 2+ homeostasome. Ca2+ triggers life at fertilization and controls the development and differentiation of cells into specialized types. It mediates the subsequent activity of these cells and, finally, is invariably involved in cell death. To coordinate all of these functions, Ca2+ signals need to be flexible yet precisely regulated. This incredible versatility arises through the use of a Ca2+- signaling ‘toolkit’, whereby the ion can act in the various contexts of space, time and amplitude. Different cell types then select combinations of Ca2+ signals with the precise parameters to fit their physiology. The concentration of Ca2+ increases during perturbation of stimuli, which get recognized by calcium binding proteins or sensor proteins. These proteins further transfer the signal downstream to start phosphorylation cascade that ultimately leads to the regulation of gene expression The modulation in Ca2+ concentration across the cell membrane is basically mediated by three classes of transporters- 1. Ca2+-ATPases (PMCAs) 2. Ca2+ permeable channels, or in other words : Ca2+ selective channels 3. Ca2+/cation antiporters (CaCAs), or in other words : Ca2+/H+ and Na+/Ca2+ exchangers which only function in combination of each other This is a interdependent system ! Otangelo Grasso

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