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a) Metabolism
Chapter 2 focused on chemical reactions, Chapter 3 brought in the concept of information and function and Chapter 4 provided a description of the main precursor biomolecules used by organisms for structure, signalling and energy production. We thus have the conceptual toolkit to progress up the complexity hierarchy and study the macroprocesses entailing series of life-sustaining chemical reactions captured under the term of metabolism. The main distinction between those macroprocesses lies in their function, whether it is to release energy, store energy, split compounds into their precursors or on the contrary use those precursors as the basis for more complex macromolecules.
The release of energy and the splitting of compounds both involve the breakdown of large molecules and are categorized as catabolic reactions. The etymology of catabolic means “thrown downward”, suggesting breaking down, whereas the opposite type of reactions are called anabolic, which translates into “thrown upward”, thus pointing to a build-up. A key example of catabolic process is glycolysis, the conversion of glucose into pyruvate. This reaction frees up energy that is then used for the production of ATP, the high-energy molecule employed by our cells to power many functions, as described in Section 4.c. Pyruvate is not just a by-product; it can be converted to fatty acids or back into carbohydrates via gluconeogenesis, the process of glucose creation. Ultimately, from the point of view of the organism, the purpose of a specific catabolic reaction is to provide either the energy (typically by oxidation) or the precursor molecules required for anabolic reactions resulting in the synthesis of different chemical compound such as the amino acids required for genetic material and the manufacturing of proteins, or the synthesis of glycogen used for energy storage.
Frequently enough, some of the compounds resulting from metabolic processes cannot be reused and are then excreted out of the organism, for instance CO2, water or nitrogenous wastes such as ammonia and urea. Conversely, some of the nutrients required by organisms to sustain themselves must be sought from outside, in food sources, as is the case for certain vitamins. Likewise, food is a source of energy – mostly in the form of carbohydrates – and molecular compounds that will be catabolized to generate the required precursor molecules as part of a metabolic pathway called digestion, which will be covered in Series 2 Chapter 2.
If we are to take a step back and conceptualize the main functions of metabolism, we could arrange them into three categories: firstly, the extraction of energy and use of this energy to perform various tasks; secondly, the breaking down of certain compounds through biochemical reactions and use of those monomers to build complex compounds and structures; and thirdly, the elimination of wastes originating from the previous two processes.
I have already used the term “metabolic pathway” repeatedly, there is nothing technical about it and it should only be understood as a series of linked chemical reactions shuttling the organism from point A to B, chemically speaking. The regulation of those processes is sometimes intrinsic, i.e. self-regulating, or it can rely on chemical messengers such as hormones and vitamins. A hormone is a signalling molecule used by complex organisms to carry information in another part of the organism from which it originates. For example, insulin is an anabolic hormone produced in the liver and this protein is primarily used to regulate the absorption of glucose from the blood for conversion into carbohydrates (including fat). Finally, the intensity and speed of the chemical reactions can be greatly enhanced by drawing upon enzymes such as lactase that excels at breaking down lactose or rubisco which is involved in the carbon fixation part of photosynthesis in plants. In case your harboured any doubt, enzymes are proteins. No prize for guessing.
For those interested, I have included a link to the Wikipedia entry on metabolic pathway at the bottom of this chapter. The article includes an impressive diagram showing the complexity and interconnectedness of the main pathways in living organisms.
b) Motility and information transfer
Metabolism explains manufacturing processes; however it doesn’t address the challenge of bringing the catabolic inputs and dispatching the anabolic outputs. For this we must turn to the concept of motility, the ability of an organism or some of its constituting parts to move using energy produced by some of this organism’s metabolic pathways. The word should not be mistaken with “mobility”, which suggests the ability to be moved but doesn’t also include the self-locomotion aspect in its definition.
Motility comes in different forms with the main types of movements used by eukaryotic organisms being flagellar propulsion, and amoeboid movement. The first in the list relies on mechanical propulsion created by the whip-like movement of a filament appendage. Think tadpoles or sperm cells but this mechanism is also used by some bacteria and archaea species. As for amoeboid, it consists in a forward protrusion within a cell adhering to a surface and forming an anchor point that is used to pull the cell forward through deformation, and so on. This is generally described as a crawling-like movement, yet one could also think of a freestyle swimmer extending his arm forward and catching the water before pulling the body into a gliding motion then growing another arm at the front of the cell, extending it forward and so forth.
In terms of orientation, the organisms or one of their molecular subsets, can be guided either by a gradient or a force field. A gradient is essentially a differential in concentration that can be of a chemical or thermic nature for instance. Therefore, a gradient will create a flow that can be leveraged as a directional axis. On the other hand, a field line can be, inter alia, magnetic or electric and would be detected by an electromagnetic sensing mechanism.
In the case of humans and other highly complex animals, the locomotion of the entire organism would have evolved to seek nutrients in various food sources through hunting or harvesting as well as to escape or fight off predators. The motility is mechanically ensured by the musculoskeletal system, which also provides stability for the organism, with the overall information processing and dispatching coordinated by the central nervous system. As mentioned earlier, some of the information carriers or signalling biomolecules used within and without the nervous systems include neurotransmitters and hormones.
Neurotransmitters are amino acids, or amino acid-based biomolecules, generally synthesized by neuronal cells and carried across synapses by vesicles where they interact with receptor proteins to which they bind perfectly, as we saw in Section 4.d.
As for hormones, they are responsible for regulating various processes, also by binding to specific receptor proteins. Unlike neurotransmitters however, they are not specific to the nervous systems and are used to convey signals at a distance, meaning to different parts of an organism, and they do so at speeds that are a very small fraction of neural signals. The class of hormones is defined functionally rather than by its make-up so they can include proteins, amino acid derivatives such as adrenaline (increases blood flow and blood sugar level, among other effects), steroids such as oestrogen (a sex hormone involved in sexual phenotypes and the regulation of the female reproductive system), or even gases such as ethylene (a plant hormone that stimulates the ripening of fruits and opening of flowers). The workings of the nervous system, including neurotransmitters, will be covered in Series 2 Chapter 6 and the musculoskeletal system in S2 Chapter 3.
c) Cellular cycle and differentiation
We now appreciate how an organism can sustain itself thanks to various metabolic pathways, not in minute details to be sure but the big picture abstract view. We also have a base-level understanding of how such an organism, or some of its parts, can move to perform specific functions as well as the role of signalling and more broadly of information transfer in getting the right tasks performed at the right time. Nevertheless, we have not yet explored the various processes leading from the cell with its DNA material (covered in Chapter 4) to a multi-cellular and complex organism. These can be categorized into two distinct types of development: the growth and division of cells as part of the cell cycle and cellular differentiation.
The eukaryotic cell cycle is usually described as being divided in two parts: interphase and mitosis though, as the term suggests, it is a cycle so during the growth phase of an organism, once a cell will be duplicated after mitosis, it and its duplicate can journey into the interphase, etc.
The interphase is best described as encompassing a growth in size and content ending with the replication of the genetic material within, the DNA. Scientific descriptions generally slice the timeline for this whole process into three distinct subphases, starting with G1, a period of growth during which the cell ramps up its protein production and the number of its organelles such as ribosomes. A series of checks then takes place and if everything went according to plan, all redacted in the codons, the S phase then gets underway. This is the period when DNA synthesis takes places resulting in a duplication of chromosomes forming sister chromatids. Another growth phase named G2 then follows, it is characterised by further protein synthesis and potential DNA repair. One more check takes place before mitosis, also known as the M phase.
Mitosis is the phase when the division of the cell occurs, after all the much lengthier preparatory work of the interphase. Mitosis shouldn’t be confused with meiosis, the process described in Section 3.d which has both a different context and outcome. Indeed, meiosis is specific to germ cells and sexual reproduction while mitosis isn’t and occurs post-fertilization onward during the life of an organism. In addition, meiosis involves chromosome recombination and mitosis does not. The purpose of those processes is therefore fundamentally different.
Returning to our description, the chromosomes that were duplicated during the S phase condense and align along a central line and the sister chromatids of those chromosomes are then split at the centre and pulled to opposite side of each cell. In parallel, the nucleus would have dissolved (in animal species at least) and will re-form later around the two sets of identical DNA material whilst the cytoplasm is cleaved in two to form two daughter cells, each with their own nucleus.
Most cells in humans are produced via mitosis, with the bulk occurring post fertilization, during embryogenesis. In the initial period, cells divide every 12-24 hour and the embryo formation goes through different stages as its size increases. Notably, cell differentiation starts as early as the third week in human embryos, thus changing the shape, size and function of cells depending on which organ they end up belonging to. Since DNA itself is normally not altered, the difference between the job each individual cell is tasked with is a function of gene expression and regulation (explained in Section 3.c, which of course relies on signalling within the organism.
An undifferentiated cell is called a stem cell and can be duplicated indefinitely. Stem cells are mostly found at the embryonic stage but also act as back up cells in some niche locations in adults. Once they specialize, as a result of gene expression, the undifferentiated stem cells become differentiated somatic cells. In the human body, there are about 220 types of differentiated cells, each with a different pattern of gene expression, from blood cells to bones and internal organs. This isn’t an all or nothing differentiation however and some cells retain intermediate degrees of differentiation potential. At the apex for animal species at the adult stage are embryonic stem cells, they are pluripotent and can differentiate in all adult cell types.
All good things come to an end, and it is no different for cells, eventually they die, either by accident or in a programmed manner. The latter generally follows one of two regulated processes: apoptosis or autophagy. Symptoms of apoptosis include the fragmentation of the nucleus or DNA and the degradation of the cell’s internal structure. This process can be a standard part of the development of an embryo into adulthood or it can be triggered following DNA damage beyond the cell’s repair capability, possibly following a replication error or an infection. On the other hand, autophagy is a catabolic process mediated by enzymes such as lysosome during which the organelles are broken down, the nucleus destroyed and the resulting chemical elements are recycled by the organism.
d) Organisms
Cellular multiplication and differentiation, check. Information transfer, movement and metabolism, check. So far, we understand the basis of the key processes that can get us from a single cell to a life sustaining complex organism. But why did evolution go this way? It was not a given considering the complexity involved and the existence of simpler forms of life such as bacteria or even viruses, if that counts, are testament that survival and replication do not solely hinge on such complexity.
The answer must of course be sought in natural selection, so the real question requires the following rephrasing: what are the relative competitive advantages of a complex organism? If relative complexity provides a reproductive or survival advantage then, incrementally, this will eventually translate into mutations coming to dominate in the genome and becoming the wild type (meaning the standard version of a gene), thus paving the way towards increasing complexity, bit by bit.
As a matter of fact, I already went through that very reasoning in Section 3.e when explaining evolution. Nevertheless, it is so central to the argument that I will quickly outline the logic using a couple of examples focusing on cell differentiation rather than the genetic diversity provided by DNA recombination through sexual reproduction.
The first illustration would be the gradual development of the musculoskeletal system permitting flight in the form of wings. This elaborate organ did not appear overnight following a single mutation and would have seen the combination of an outgrowth to an existing pair of limbs, perhaps the equivalent of our arms, permitting an animal to glide a little bit, when jumping from a branch trying to escape a predator, to hunt a prey or harvest some fruit from a tree branch. The minute increase in survival rate provided by even the smallest of advantages to individuals carrying this mutation in their genome will statistically, over generations, ensure this modified version of the original gene becomes the wild type, “the new normal”. Over time, some of those descendants will experience another beneficial mutation that would have further enhanced the original advantage, possibly by making this limb-like protrusion longer so that the gliding becomes more pronounced. And so on. At some stage, one those mutations would have altered the skeleton or muscle involved in moving the arm so that it developed a minor ability to flap and extend the glide, and so forth until we have an airborne organism. Based on scientific research, it seems flight has evolved at least four times independently: in birds, in pterosaurs during the Mesozoic era, in insects and in bats. “At least” because some species may have become instinct and not made it to the fossil record (or those fossils have not yet been unearthed or have degraded beyond a level fit for analysis).
For our second example we can select any internal organ – say the lungs, rather than the more obvious central nervous system. In theory, single cells relying on oxygen to power their metabolism will evolve in an environment where it can be found and the carbon dioxide they produce may be excreted. Yet, as the organism enlarges, this may become problematic for those cells that are not situated on the periphery. In comparison, having a dedicated, specialized set of cells developing to the point of becoming a fully-fledged organ and having perfected the art of extracting oxygen from the atmosphere and releasing the carbon dioxide by-product outside of the organism will result in a stepping up of the intensity and efficiency of its overall metabolism, thus providing a relative advantage compared to organisms who have not evolved such an organ, or not to the same extent. The particular mechanisms of gas exchanges of the lung would of course not be what they are, nor would they perform so well, had they not evolved in combination with the cardiovascular system and the diaphragm skeletal muscle.
The standard way to think about an organism is in relation with its physical limits, as a distinct living entity separated in space and movement from other organisms. This works, in many ways, but if we go back to the notion of extended phenotype, we can see that the concept of organism can also extend to a collaboration between a set of individual organisms. Think beehive, ant colony, a corporation with its decision centre and specialized departments, or even a country.
This blurring of the lines and the multiplicity of configurations makes it hard to come up with a precise definition, especially as there may be an element of subjectivity in establishing fixed criteria. And it turns out, I am in the camp of those who say it doesn’t matter if there is no agreed upon set-in-stone definition. Ultimately, the concept of organism is an abstraction, not a hard fact of nature. And when we peel the layers, one by one, it is always about forces and information, not much else.
e) Life and death
This provides a suitable segue for how to think about life. The idea of an entity experiencing chemical reactions, a phenomenon directly related to the existence of fundamental interactions (also known as fundamental forces), cannot be enough to qualify – otherwise pretty much any compound could be said to be alive. This means the notion of information has to be central and, indeed, order or the decrease in entropy is a direct consequence of the existence and usage of information.
Life occurs when the virtual cycle between chemical reactions and information is maintained so that an organism can sustain its biological processes and not degrade beyond a point of no repair. The flip side is death, when a trauma, decay or infection prevents the retention and transfer of information required for maintaining homeostasis. An irreversible increase in entropy ensues.
Homeostasis is a crucial concept in biology, it is essentially about the maintenance of the internal variables within an organism which ensure all the physical and chemical processes required for a continuous existence can be properly carried out. Key variables include the pH level (a measure of the acidity of an aqueous solution), blood sugar level, body temperature, or the concentration of ions and other chemical elements such as potassium and sodium. For a successful homeostasis, there needs to be appropriate receptors in place, decisions taken based on the measured levels of the multiple variables, and an adequate response or rectification needs to be implemented. That regulation never stops and when it goes awry there tends to be unenjoyable consequences, with death on the approaching horizon.
In a manner reminiscent of organisms, the unanswered question of whether viruses are alive exhibits the difficulty in phrasing a hard-edged definition of life. My point of view is also identical to the question of how to define the true nature of an organism: it doesn’t really matter because life is also an abstraction dreamed up by humans. Accordingly, it may not always fit precisely with some of nature edge cases.
f) Trivia – Bee hives
In a hive of honeybees, there is only one sexually mature female who lays eggs, the worker bees are not. This ought to be surprising since at birth the royal and worker larvae are indistinguishable – that bit however should not be surprising given they are the same species. So, what happens behind the beeswax?
The secret, the factor triggering the difference, is the diet that future queen bee larvae are fed. It is made exclusively of royal jelly which contains nutriments that will have an impact in terms of metabolism and gene regulation by prompting a different pattern of gene expression and phenotypic differences compared to the worker bees; in particular this will lead to the full development of its reproductive organs, something not taking place with the lay workers.
In that respect, the queen bee can be thought of as the reproductive organ in the beehive, so it really isn’t far-fetched to think of a beehive or colony as a type of biological organism.
g) Further reading (S1C5)
Suggested reads:
- Wikipedia on Metabolic pathway: https://en.wikipedia.org/wiki/Metabolic_pathway
- Wikipedia on Cell cycle: https://en.wikipedia.org/wiki/Cell_cycle
- Wikipedia on Homeostasis: https://en.wikipedia.org/wiki/Homeostasis
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