Econstudentlog

Systems Biology (I)

This book is really dense and is somewhat tough for me to blog. One significant problem is that: “The authors assume that the reader is already familiar with the material covered in a classic biochemistry course.” I know enough biochem to follow most of the stuff in this book, and I was definitely quite happy to have recently read John Finney’s book on the biochemical properties of water and Christopher Hall’s introduction to materials science, as both of those books’ coverage turned out to be highly relevant (these are far from the only relevant books I’ve read semi-recently – Atkins introduction to thermodynamics is another book that springs to mind) – but even so, what do you leave out when writing a post like this? I decided to leave out a lot. Posts covering books like this one are hard to write because it’s so easy for them to blow up in your face because you have to include so many details for the material included in the post to even start to make sense to people who didn’t read the original text. And if you leave out all the details, what’s really left? It’s difficult..

Anyway, some observations from the first chapters of the book below.

“[T]he biological world consists of self-managing and self-organizing systems which owe their existence to a steady supply of energy and information. Thermodynamics introduces a distinction between open and closed systems. Reversible processes occurring in closed systems (i.e. independent of their environment) automatically gravitate toward a state of equilibrium which is reached once the velocity of a given reaction in both directions becomes equal. When this balance is achieved, we can say that the reaction has effectively ceased. In a living cell, a similar condition occurs upon death. Life relies on certain spontaneous processes acting to unbalance the equilibrium. Such processes can only take place when substrates and products of reactions are traded with the environment, i.e. they are only possible in open systems. In turn, achieving a stable level of activity in an open system calls for regulatory mechanisms. When the reaction consumes or produces resources that are exchanged with the outside world at an uneven rate, the stability criterion can only be satisfied via a negative feedback loop […] cells and living organisms are thermodynamically open systems […] all structures which play a role in balanced biological activity may be treated as components of a feedback loop. This observation enables us to link and integrate seemingly unrelated biological processes. […] the biological structures most directly involved in the functions and mechanisms of life can be divided into receptors, effectors, information conduits and elements subject to regulation (reaction products and action results). Exchanging these elements with the environment requires an inflow of energy. Thus, living cells are — by their nature — open systems, requiring an energy source […] A thermodynamically open system lacking equilibrium due to a steady inflow of energy in the presence of automatic regulation is […] a good theoretical model of a living organism. […] Pursuing growth and adapting to changing environmental conditions calls for specialization which comes at the expense of reduced universality. A specialized cell is no longer self-sufficient. As a consequence, a need for higher forms of intercellular organization emerges. The structure which provides cells with suitable protection and ensures continued homeostasis is called an organism.”

“In biology, structure and function are tightly interwoven. This phenomenon is closely associated with the principles of evolution. Evolutionary development has produced structures which enable organisms to develop and maintain its architecture, perform actions and store the resources needed to survive. For this reason we introduce a distinction between support structures (which are akin to construction materials), function-related structures (fulfilling the role of tools and machines), and storage structures (needed to store important substances, achieving a compromise between tight packing and ease of access). […] Biology makes extensive use of small-molecule structures and polymers. The physical properties of polymer chains make them a key building block in biological structures. There are several reasons as to why polymers are indispensable in nature […] Sequestration of resources is subject to two seemingly contradictory criteria: 1. Maximize storage density; 2. Perform sequestration in such a way as to allow easy access to resources. […] In most biological systems, storage applies to energy and information. Other types of resources are only occasionally stored […]. Energy is stored primarily in the form of saccharides and lipids. Saccharides are derivatives of glucose, rendered insoluble (and thus easy to store) via polymerization.Their polymerized forms, stabilized with α-glycosidic bonds, include glycogen (in animals) and starch (in plantlife). […] It should be noted that the somewhat loose packing of polysaccharides […] makes them unsuitable for storing large amounts of energy. In a typical human organism only ca. 600 kcal of energy is stored in the form of glycogen, while (under normal conditions) more than 100,000 kcal exists as lipids. Lipids deposit usually assume the form of triglycerides (triacylglycerols). Their properties can be traced to the similarities between fatty acids and hydrocarbons. Storage efficiency (i.e. the amount of energy stored per unit of mass) is twice that of polysaccharides, while access remains adequate owing to the relatively large surface area and high volume of lipids in the organism.”

“Most living organisms store information in the form of tightly-packed DNA strands. […] It should be noted that only a small percentage of DNA (about few %) conveys biologically relevant information. The purpose of the remaining ballast is to enable suitable packing and exposure of these important fragments. If all of DNA were to consist of useful code, it would be nearly impossible to devise a packing strategy guaranteeing access to all of the stored information.”

“The seemingly endless diversity of biological functions frustrates all but the most persistent attempts at classification. For the purpose of this handbook we assume that each function can be associated either with a single cell or with a living organism. In both cases, biological functions are strictly subordinate to automatic regulation, based — in a stable state — on negative feedback loops, and in processes associated with change (for instance in embryonic development) — on automatic execution of predetermined biological programs. Individual components of a cell cannot perform regulatory functions on their own […]. Thus, each element involved in the biological activity of a cell or organism must necessarily participate in a regulatory loop based on processing information.”

“Proteins are among the most basic active biological structures. Most of the well-known proteins studied thus far perform effector functions: this group includes enzymes, transport proteins, certain immune system components (complement factors) and myofibrils. Their purpose is to maintain biological systems in a steady state. Our knowledge of receptor structures is somewhat poorer […] Simple structures, including individual enzymes and components of multienzyme systems, can be treated as “tools” available to the cell, while advanced systems, consisting of many mechanically-linked tools, resemble machines. […] Machinelike mechanisms are readily encountered in living cells. A classic example is fatty acid synthesis, performed by dedicated machines called synthases. […] Multiunit structures acting as machines can be encountered wherever complex biochemical processes need to be performed in an efficient manner. […] If the purpose of a machine is to generate motion then a thermally powered machine can accurately be called a motor. This type of action is observed e.g. in myocytes, where transmission involves reordering of protein structures using the energy generated by hydrolysis of high-energy bonds.”

“In biology, function is generally understood as specific physiochemical action, almost universally mediated by proteins. Most such actions are reversible which means that a single protein molecule may perform its function many times. […] Since spontaneous noncovalent surface interactions are very infrequent, the shape and structure of active sites — with high concentrations of hydrophobic residues — makes them the preferred area of interaction between functional proteins and their ligands. They alone provide the appropriate conditions for the formation of hydrogen bonds; moreover, their structure may determine the specific nature of interaction. The functional bond between a protein and a ligand is usually noncovalent and therefore reversible.”

“In general terms, we can state that enzymes accelerate reactions by lowering activation energies for processes which would otherwise occur very slowly or not at all. […] The activity of enzymes goes beyond synthesizing a specific protein-ligand complex (as in the case of antibodies or receptors) and involves an independent catalytic attack on a selected bond within the ligand, precipitating its conversion into the final product. The relative independence of both processes (binding of the ligand in the active site and catalysis) is evidenced by the phenomenon of noncompetitive inhibition […] Kinetic studies of enzymes have provided valuable insight into the properties of enzymatic inhibitors — an important field of study in medicine and drug research. Some inhibitors, particularly competitive ones (i.e. inhibitors which outcompete substrates for access to the enzyme), are now commonly used as drugs. […] Physical and chemical processes may only occur spontaneously if they generate energy, or non-spontaneously if they consume it. However, all processes occurring in a cell must have a spontaneous character because only these processes may be catalyzed by enzymes. Enzymes merely accelerate reactions; they do not provide energy. […] The change in enthalpy associated with a chemical process may be calculated as a net difference in the sum of molecular binding energies prior to and following the reaction. Entropy is a measure of the likelihood that a physical system will enter a given state. Since chaotic distribution of elements is considered the most probable, physical systems exhibit a general tendency to gravitate towards chaos. Any form of ordering is thermodynamically disadvantageous.”

“The chemical reactions which power biological processes are characterized by varying degrees of efficiency. In general, they tend to be on the lower end of the efficiency spectrum, compared to energy sources which drive matter transformation processes in our universe. In search for a common criterion to describe the efficiency of various energy sources, we can refer to the net loss of mass associated with a release of energy, according to Einstein’s formula:
E = mc2
The
M/M coefficient (relative loss of mass, given e.g. in %) allows us to compare the efficiency of energy sources. The most efficient processes are those involved in the gravitational collapse of stars. Their efficiency may reach 40 %, which means that 40 % of the stationary mass of the system is converted into energy. In comparison, nuclear reactions have an approximate efficiency of 0.8 %. The efficiency of chemical energy sources available to biological systems is incomparably lower and amounts to approximately 10(-7) % […]. Among chemical reactions, the most potent sources of energy are found in oxidation processes, commonly exploited by biological systems. Oxidation tends  to result in the largest net release of energy per unit of mass, although the efficiency of specific types of oxidation varies. […] given unrestricted access to atmospheric oxygen and to hydrogen atoms derived from hydrocarbons — the combustion of hydrogen (i.e. the synthesis of water; H2 + 1/2O2 = H2O) has become a principal source of energy in nature, next to photosynthesis, which exploits the energy of solar radiation. […] The basic process associated with the release of hydrogen and its subsequent oxidation (called the Krebs cycle) is carried by processes which transfer electrons onto oxygen atoms […]. Oxidation occurs in stages, enabling optimal use of the released energy. An important byproduct of water synthesis is the universal energy carrier known as ATP (synthesized separately). As water synthesis is a highly spontaneous process, it can be exploited to cover the energy debt incurred by endergonic synthesis of ATP, as long as both processes are thermodynamically coupled, enabling spontaneous catalysis of anhydride bonds in ATP. Water synthesis is a universal source of energy in heterotrophic systems. In contrast, autotrophic organisms rely on the energy of light which is exploited in the process of photosynthesis. Both processes yield ATP […] Preparing nutrients (hydrogen carriers) for participation in water synthesis follows different paths for sugars, lipids and proteins. This is perhaps obvious given their relative structural differences; however, in all cases the final form, which acts as a substrate for dehydrogenases, is acetyl-CoA“.

“Photosynthesis is a process which — from the point of view of electron transfer — can be treated as a counterpart of the respiratory chain. In heterotrophic organisms, mitochondria transport electrons from hydrogenated compounds (sugars, lipids, proteins) onto oxygen molecules, synthesizing water in the process, whereas in the course of photosynthesis electrons released by breaking down water molecules are used as a means of reducing oxydised carbon compounds […]. In heterotrophic organisms the respiratory chain has a spontaneous quality (owing to its oxidative properties); however any reverse process requires energy to occur. In the case of photosynthesis this energy is provided by sunlight […] Hydrogen combustion and photosynthesis are the basic sources of energy in the living world. […] For an energy source to become useful, non-spontaneous reactions must be coupled to its operation, resulting in a thermodynamically unified system. Such coupling can be achieved by creating a coherent framework in which the spontaneous and non-spontaneous processes are linked, either physically or chemically, using a bridging component which affects them both. If the properties of both reactions are different, the bridging component must also enable suitable adaptation and mediation. […] Direct exploitation of the energy released via the hydrolysis of ATP is possible usually by introducing an active binding carrier mediating the energy transfer. […] Carriers are considered active as long as their concentration ensures a sufficient release of energy to synthesize a new chemical bond by way of a non-spontaneous process. Active carriers are relatively short-lived […] Any active carrier which performs its function outside of the active site must be sufficiently stable to avoid breaking up prior to participating in the synthesis reaction. Such mobile carriers are usually produced when the required synthesis consists of several stages or cannot be conducted in the active site of the enzyme for sterical reasons. Contrary to ATP, active energy carriers are usually reaction-specific. […] Mobile energy carriers are usually formed as a result of hydrolysis of two high-energy ATP bonds. In many cases this is the minimum amount of energy required to power a reaction which synthesizes a single chemical bond. […] Expelling a mobile or unstable reaction component in order to increase the spontaneity of active energy carrier synthesis is a process which occurs in many biological mechanisms […] The action of active energy carriers may be compared to a ball rolling down a hill. The descending snowball gains sufficient energy to traverse another, smaller mound, adjacent to its starting point. In our case, the smaller hill represents the final synthesis reaction […] Understanding the role of active carriers is essential for the study of metabolic processes.”

“A second category of processes, directly dependent on energy sources, involves structural reconfiguration of proteins, which can be further differentiated into low and high-energy reconfiguration. Low-energy reconfiguration occurs in proteins which form weak, easily reversible bonds with ligands. In such cases, structural changes are powered by the energy released in the creation of the complex. […] Important low-energy reconfiguration processes may occur in proteins which consist of subunits. Structural changes resulting from relative motion of subunits typically do not involve significant expenditures of energy. Of particular note are the so-called allosteric proteins […] whose rearrangement is driven by a weak and reversible bond between the protein and an oxygen molecule. Allosteric proteins are genetically conditioned to possess two stable structural configurations, easily swapped as a result of binding or releasing ligands. Thus, they tend to have two comparable energy minima (separated by a low threshold), each of which may be treated as a global minimum corresponding to the native form of the protein. Given such properties, even a weakly interacting ligand may trigger significant structural reconfiguration. This phenomenon is of critical importance to a variety of regulatory proteins. In many cases, however, the second potential minimum in which the protein may achieve relative stability is separated from the global minimum by a high threshold requiring a significant expenditure of energy to overcome. […] Contrary to low-energy reconfigurations, the relative difference in ligand concentrations is insufficient to cover the cost of a difficult structural change. Such processes are therefore coupled to highly exergonic reactions such as ATP hydrolysis. […]  The link between a biological process and an energy source does not have to be immediate. Indirect coupling occurs when the process is driven by relative changes in the concentration of reaction components. […] In general, high-energy reconfigurations exploit direct coupling mechanisms while indirect coupling is more typical of low-energy processes”.

Muscle action requires a major expenditure of energy. There is a nonlinear dependence between the degree of physical exertion and the corresponding energy requirements. […] Training may improve the power and endurance of muscle tissue. Muscle fibers subjected to regular exertion may improve their glycogen storage capacity, ATP production rate, oxidative metabolism and the use of fatty acids as fuel.

February 4, 2018 - Posted by | Biology, Books, Chemistry, Genetics, Molecular biology, Pharmacology, Physics

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