How intracellular 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 nano molar, 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 sulphate. 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 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 make of a power gradient ( which is a thermodynamically uphill process ) is always a 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 knowledged engineers of large companies. As for many human inventions, the engineering solutions discovered by man are employd in nature at least since life began in a far more elaborated and sophisticated way. [color=#009900]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 a ambience prerequisite, homeostasis of various elements, to permit life ?[/color]
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 exist 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 fulfil the tasks assigned to them. The balance of Ca2+ between cells and the outside ambient must be regulated with outmost 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+( manganese ).