These are my notes and review for this book. For other reading notes see tag: books
These are my notes and excerpts from 'The Machinery of Life', by David S. Goodsell. This was one of the few books on biology -not my field of expertise- I read.
The Machinery of Life is a short book packed full of beautiful illustrations, which I feel gave me a better intuition of what a cell looks like under a microscope than the typically simplified diagrams I would see in highschool. I loved the illustrations but the pictures of standalone proteins sometimes felt like they didn’t add anything to the conversation and turned a bit repetitive.
The text itself was full of interesting descriptions and explained some key mechanisms in cellular life, like protein synthesis, the actions of the immune system, and the importance of certain nutrients or proteins. I felt at times that I would’ve liked a more detailed explanation of some mechanisms, like with cellular death or the impact of hydroxils and superoxygen in proteins, but the book was generally satisfactory as a shallow dive into biology for someone who is not too acquainted with the field.
I give it a 7/10.
What follow are my notes for each chapter. They consist mostly of quotes or rephrasings of key explanations and interesting facts, in the order they were presented in the book.
The last joint in your finger is about 1000 cells long. A similar proportion to how many grains of rice fit accross the side of a room –you could say a room is 1000 rice grains long. The same way, the quantity of proteins that fit in a cell is also around 1 billion -1000 proteins long, 1000 wide, 1000 tall-.
A cell full of proteins is like a room full of rice.
However, a protein moves through a cell (in a completely random walk) at about a million times its own length every second.
“You might ask how anything ever gets done in this chaotic world. It is true that the motion is random, but it is also true that the motion is very fast compared to the motion in our familiar world.
Random, diffusive motion is fast enough to perform most of the tasks in the cell. Each molecule simply bumps around until it finds the right place.
To get an idea of how fast this motion is, imagine a typical bacterial cell, and place an enzyme at one end and a sugar molecule at the other. They will bump around and wander through the whole cell, encountering many molecules along the way. On average, though, it will only take about a second for those two molecules to bump into each other at least once. This is truly remarkable: this means that any molecule in a typical bacterial cell, during its chaotic journey through the cell, will encounter almost every other molecule in a matter of seconds.”
“Modern cells use four basic plans for combining atoms to make molecular machines. Whereas our familiar machines are built of metal, wood, plastic, and ceramic, the nanoscale machinery of cells is built of protein, nucleic acid, lipid, and polysaccharide. Each of these plans has a unique chemical personality ideally suited to a different role in the cell. Two basic concepts are needed to understand how this chemical personality is manifested: chemical complementarity and hydrophobicity.”
The large molecular machines in cells take advantage of both of these properties. They often have oddly shaped surfaces that use hydrogen bonds and salt bridges to find molecules with complementary shapes. They often have both hydrophilic and hydrophobic regions that interact differently with water. Different patterns of these regions cause molecules to act in novel ways when dissolved in water.
The book classifies molecules into 4 categories, which have distinct properties:
Nucleic Acids : Each nucleotide is composed of a base (A, T, C or G), which includes the hydrogen-bonding atoms held together in the perfect orientation in a rigid ring, and a sugar-phosphate group, which is used to link the nucleotides together.
Nucleic acids, are too limited in structure to perform the many tasks in the daily life of a cell. The chemistry of the four bases, although perfect for information transfer, are too similar to allow the construction of the varied machines needed to perform thousands of different chemical and mechanical reactions. Instead, proteins are used in this capacity.
Proteins: Like nucleic acids, proteins are long molecular chains, but instead of using four chemically similar nucleotides, proteins are built of 20 different amino acids, each with a different size and chemical character. They can serve multiple functions: some jut take a certain shape, some move and rotate, some are catalysts for a chemical reaction, moving atoms around.
The final shape of the folded protein is completely predetermined by the order of amino acids in the protein chain. In water, proteins tend to fold to expose hidrophilic aminoacids and cover hydrophobic ones.
A typical bacterium builds several thousand different types of proteins, each with a different function. Our own cells build about 30,000 different kinds, ranging in size from small protein hormones like glucagon, which has only 29 amino acids, to huge proteins like titin, which has over 34,000 amino acids.
Side fun fact: antibodies are proteins.
Lipids: Individually, lipids are tiny molecules, but when grouped together, they form the largest structures of the cell.
When placed in water, lipid molecules aggregate to form huge waterproof sheets. These sheets are used to enclose cells, forming the primary boundary separating the inside of the cell from the environment. They are also used to build compartments inside cells, such as the nucleus and the mitochondria. The unusual interaction of lipids with water makes them so useful. Lipids, known commonly as fats and oils, are composed of a small hydrophilic ‘‘head’’ connected to two or three long hydrophobic ‘‘tails.’’
In cells, the lipids aggregate to form a lipid bilayer: a continuous sheet composed of two layers of aligned lipids. All the tails pack side-by-side in the center and the heads are displayed on the two faces, comfortable in the surrounding water.
Since lipid bilayers are composed of so many separate molecules, they are dynamic and fluid. Each individual molecule rotates like a top, and its hydrophobic tails wag and flail. Lipids also slide rapidly past one another, always staying in the sheet, but randomly migrating sideways. Since they are so fluid, lipid bilayers make the perfect skin for cells. The membrane is flexible and bends easily to meet the demands of the cell.
Pure lipid bilayers, however, are rarely found in modern cells. After all, a perfect barrier would seal the cell away from food and nutrients, and seal in waste materials. To solve this problem, cells build a variety of specialized proteins that are inserted into the membrane.
Polysaccharides: Long chains of sugars, used by organisms to make resilient and malleable structures like cellulose (wood, paper), insect carapaces or exoskeletons (chitin), and structural material in general.
“To make things even more challenging, cells must also be able to make all of their component molecular machines using only the resources that are available in the local environment. Think of the magnitude of this accomplishment. Many bacteria are able to build all of their own molecules from the a few simple raw materials like carbon dioxide, oxygen, and ammonia. A single bacterial cell knows how to build several thousand types of proteins, including motors, girders, toxins, catalysts, and construction machinery. This cell also builds hundreds of RNA molecules with different orderings of nucleotides, as well as a diverse collection of lipids, sugar polymers, and a bewildering collection of exotic small molecules. All of these different molecules must be created from scratch, using only the molecules that the cell eats, drinks, and breathes.”
At a rate of about 20 amino acids per second, an average protein takes about 20 seconds to build.
“As with the breakdown of sugar, molecular machines perform energetic processes in small steps. Chemical energy is obtained through reactions of single molecules. Electrochemical energy is stored by moving individual ions, light is captured one photon at a time, and electrons are moved one-by-one along a string of molecular electron carriers. This allows a level of control, and efficiency, that is rarely seen in our familiar macroscale world.”
About E. Coli, a very common, easy to grow and fast growing bacteria that’s been widely studied (with its whole genome and proteinome mapped).
The outer membrane also anchors many fimbriae. These long, thin protein complexes are extruded piece-by-piece through special gateway proteins in the outer membrane. Fimbriae have sticky ends, and when the bacterium finds an amenable place to rest, they glue it in place. The type of fimbriae made by a particular strain is important. The fimbriae of pathogenic bacteria allow them to attach to human cells and resist attack by the cells of immune system.
Many important antibiotics, such as penicillin, kill bacterial cells by attacking the enzymes that build the peptidoglycan layer. When treated with penicillin, bacterial cells lose their shape and ultimately explode under the osmotic pressure.
DNA polymerase adds about 800 new nucleotides every second, taking about 50 min to duplicate the entire circle [of DNA]. However, in a rapidly growing Escherichia coli culture, the cells divide every half hour. This doesn’t allow enough time to duplicate the entire genome of DNA before each division. Escherichia coli cells resolve this problem by starting new DNA duplications before the previous round has finished. When a round of duplication is completed and the two circles fall apart, each new circle is already about half way through the next round of replication. Bacterial cells are truly adapted to exploit their environment!
If oxygen is available, Escherichia coli cells use a multistep system very similar to our own central system of energy production. It starts with glycolysis, a series of 10 enzymes that take glucose and break it into two pieces. As with all of the cell’s chemical transformations, glycolysis is performed in many steps, each under careful control. Two of these steps are particularly energetic, and they are used to create two molecules of ATP. Many organisms stop at this point, using the ATP for energy and discarding the pieces as alcohol (this is how the alcohol in wine and beer is created by yeast).
A bacterial cell can’t look at a distance and see what direction food lies. Instead, Escherichia coli cells use an effective combination of the swimming and tumbling properties of their flagella. Each cell uses an array of sensors to determine the level of food in theimmediate vicinity. Then it swims in a random direction, and measures the level of nutrients there. If the levels are increasing, it keeps swimming in that direction, since things are getting better. If not, the sensory array sends a signal to the flagellar motor, telling it to reverse direction. This causes the cell to tumble, picking a new (and hopefully better) direction to swim. [I love that bacteria basically move through gradient ascent].
This diversity creates an informational problem not encountered by simpler organisms. Since all of the cells in the human body are created from a single fertilized egg cell, the single copy of DNA from each parent must hold all of the information needed by every type of cell. Thus, nerve cells carry the information needed to build hemoglobin, and blood cells could conceivably make neurotransmitters. Clearly, however, this must not occur, or the result would be chaos. Each cell must be able to decide which proteins it makes and which ones it ignores, focusing on its role in the blood, brain or elsewhere.
Structurally, there are proteins like cadherin, juntional molecules, that help cells stick together and remain fixed in tissues and organs. There are also filaments and microtubules for more complex structure, like the keratin in hair or the microtubules that make up sperm’s flagella or neuron’s axons.
Messages are also passed between cells in a local neighborhood using molecular messengers, termed cytokines. These are small proteins that are built by one cell and then dropped outside the cell. They diffuse to a neighbor and are captured by receptors on the cell surface. This triggers a signal inside the cell, causing it to take appropriate action. A constant dialogue of cytokines allows cells to discuss the current state of the tissue, determining if it is time to grow or time to rest. Cytokines are also used to warn of danger. For instance, cells build alpha-interferon as a warning that there may be viruses in the vicinity.
Red blood cells are unselfishly dedicated to their work of carrying oxygen from the lungs to the tissues. In fact, they can do little else. Red blood cells are created from stem cells in the bone marrow. As they develop, they gradually shift their resources almost entirely to the building of hemoglobin, and allow all of their other functions to atrophy. The cell membrane loses much of its machinery for communication and selective transport, and is braced only by a rudimentary scaffolding that helps the cell hold its distinctive disk-like shape. Finally, the cell makes the ultimate sacrifice. It concentrates all of its normal molecular machinery—mitochondria, nucleus, ribosomes— into one corner and ejects it all from its body. The mature red blood cell, now a directionless automaton, is then placed into the bloodstream where it carries oxygen through the blood for about 4 months. [Kyou mo hakobu yo sanso sanso!]
Instead of carrying them one by one inside a protein like serum albumin, they are carried in small globules called lipoproteins. Each lipoprotein is composed of a collection of fat or lipid molecules surrounded by a ring of protein. These lipoproteins are absorbed by cells lining the circulatory system and disassembled inside. There are two major types of lipoproteins circulating in the blood: low-density lipoproteins (LDL) and highdensity lipoproteins (HDL).
Low-density lipoproteins are larger and contain more lipids, thus giving them the lower density. Both forms are important for the transport of cholesterol around the body. LDL, however, has gotten a bad reputation as ‘‘bad cholesterol,’’ since it has a tendency to build up on the walls of arteries that feed the heart and the brain, leading to atherosclerosis. High levels of HDL, on the other hand, appear to correlate with a reduced risk of heart disease, and have been dubbed ‘‘good cholesterol.’’ The exact mechanism of this protection is still a matter of controversy, but it may be due to the ability of HDL to transport of cholesterol away from plaques and back into storage in the liver.
“Decay and death are an inevitable consequence of the world that we live in. The forces of entropy wage a slow but implacable battle of erosion on everything. The major discovery made by the earliest cells, which allows life in our world of entropy, is the ability to maintain order when challenged by this inevitable decay into equilibrium”
Proteasomes are voracious protein shredders, but the protein-cutting machinery is carefully hidden away inside a barrel-shaped structure. So, the proteasome is able to wander freely inside the cell, and only the proper proteins are fed into its hungry maw.
The small protein ubiquitin plays a central role in this process. It is attached to old proteins, signaling to the cell that they are ready to be disassembled and recycled. The tricky part of this process is making sure that ubiquitin is only attached to the proper proteins.
DNA is damaged by UV rays, gamma rays and others. Even by unstable oxigen molecules.
Homologous recombination is the primary method for repairing breaks in the DNA. It relies on the fact that each cell carries a duplicate set of DNA. The break is repaired by using the duplicate set as a template to match and connect the broken strands. The central step of the process is called synapsis, where the two homologous strands— the damaged one and the undamaged template—are brought together in perfect alignment.
This amazing process is performed in our cells by the protein Rad51.
As cells divide, the DNA copy process can potentially be corrupted, and data is not copied to the end. Many bacteria combat this problem by getting rid of the ends entirely: they close their DNA into a big circle. Our cells, however, contain 46 linear strands, each with two ends that must be protected.
To solve this problem, our DNA strands have a special nucleotide sequence at each end, called a telomere. The telomere is composed of the sequence GGGTTA repeated over and over, about a thousand times in a row. After division, a random amount of telomeres may be lost. Then the enzyme telomerase binds to the telomere, and using its own internal RNA template, it extends the telomere with new copies of the repeated sequence.
Embryonic cells and stem cells, like the ones that continually produce blood cells throughout our lives, have an active telomerase that protects their DNA during replication. However, most of our cells have turned off their ability to extend telomeres.
This may help protect us from cancer, as normal cells then can only divide about 60 times before irrepairable damage occurs and the cell dies, preventing unchecked growth.
The process of programmed cell death or apoptosis, allows the cell to disassemble itself in an orderly fashion and notify the immune system that it is ready to be recycled.
Cells trigger apoptosis for many different reasons.
Programmed cell death also plays an important role in protecting us from cancer, since cells that show abnormal growth are usually forced to die.
In cancer, a cell grows aberrantly, and may even hijack the signaling processes to make neighboring cells give out resources, or even direct tissue to create blood vessels that direct nutrients to cancer tissue.
This happens when some key mutations take place simultaneously.
“For instance, one of the central oncogenes in many cancer cells is a mutation in the p53 tumor suppressor protein. It normally watches the cell for damage to the DNA and other changes that might lead to aberrant growth. If it finds damage, it can freeze the division of cells or even cause programmed cell death. Many cancer cells, however, have a mutated form of p53 tumor suppressor that is no longer effective, so the cancer is free to grow without control.”
“We start out life with a clean set of genes, all of which support the normal growth and maintenance of tissues. As we grow older, however, our genes are continually attacked by sunlight and chemicals, causing mutations at random places in the DNA. As described above, many of these mutations are corrected by our repair mechanisms, but some slip through. Many are harmless, but as we grow older and older, more and more of them build up. If just the right combination of mutations occurs in a single cell, it becomes a cancer cell and grows into a tumor.”
One of the many mechanisms behind aging is the accumulation of dangerously reactive variants of oxygen, like superoxide and hydroxyl. Cytochrome c Oxidase is the protein which generates them when it fails in its task. It performs the last step in respiration, placing the electrons extracted from food molecules onto oxygen.
Antioxidants help in the task of stabilizing these molecules. These include Vitamin C, A, E and others.
“Viruses are completely selfish. They break into cells, overpower their normal functioning, and coerce them to one task: the production of more viruses.”
Viruses have a particularly simple way of creating new viruses, a way that requires only a minimal investment of molecular machinery. All they need to do is get a copy of a viral messenger RNA into a cell. This messenger RNA encodes all of the proteins needed to manufacture and assemble the component parts of the virus.
Poliovirus and rhinovirus take a shortcut and avoid DNA altogether. They inject a viral RNA into the cell, which contains instructions for making a special RNA-dependent RNA polymerase. This viral polymerase builds RNA strands using the viral RNA strand as the template. Thus, they don’t need DNA at all—the viral RNA is copied directly to make more viral RNA.
The genomes of the poliovirus and rhinovirus are so small that only a few proteins may be encoded.
These include
The virus finds a target cell through receptors in its capsid, then injects its RNA.
Once the RNA is inside, the cell’s own ribosomes translate the RNA into a long polyprotein. This polyprotein is composed of all the viral proteins, strung together like a string of beads. The two proteases then cut themselves out of the polyprotein, and proceed to cut the rest of the proteins apart. Then, the major activity begins.
The new viral polymerase quickly begins making new copies of the viral RNA, using the cell’s reservoir of nucleotides.
One of the viral proteases seeks out a particular initiation factor used by the cell, and cuts it in half. This initiation factor is essential for protein synthesis with the cell’s own messenger RNA, so all normal protein synthesis stops.
new viruses spontaneously begin to assemble. Each one contains a new RNA molecule packaged in a coat of newly built proteins.
Finally, the cell ruptures and new viruses swarm out to infect other cells, and the cycle begins again, leaving behind all polymerase.
Vitamin D is formed from cholesterol in a reaction that requires ultraviolet light.
Since it binds so tightly, carbon monoxide is difficult to remove from poisoned blood. An hour of breathing pure oxygen will reduce the level of bound carbon monoxide by only one half. Cyanide also binds similarly to oxygen, this time to oxigenase, preventing cellular respiration.