Molecular Biology of the Cell – Notes

Key Missing Ingredients:

• Condense parts of this into nice articles. Learning without showing what I've learned out in the open is useless.
• Article Ideas:
  • Krebs Cycle
  • Free Energy and it's connections to Entropy
  • Functional groups of organic chemistry and what they do
  • How the ETC works
  • Motivational Document. Why I am doing what I am doing and how I am approaching it.
• Parse out list of words I don't know into Notion pages with Notes from reading their Wikipedia pages. Think of ways to do this out in the open as well. Maybe short YouTube videos on these things?

Structure:

Part I: Basic Biochem

Part II: Genetic Information, Storage + Manipulation

Part III: Experimental Methods used for Understanding Cells

Part IV: Internal Organization of a Cell

Part V: Multicellular Systems

Words I don't know from the Content Table:

• Nucleolus
• Ribozyme
• Chaperones
• Polyribosomes
• Retrotransposons
• Globin
• Translesion
• Topoisomerase
• Polytene
• Allosteric
• Ligand
• Nucleosome
• Ubiquitin
• Kinase
• Proteasome
• Motif
• Operon

Chapter 1 - Cells and Genomes

Life

The surface of our planet is populated by living things—curious, intricately organized chemical factories that take in matter from their surroundings and use these raw materials to generate copies of themselves.

Everything alive we know of is made out of cells. Therefore studying cells is studying how life works.

Heredity defines life. Traits can be passed on. Cells do the passing on of information through DNA. Information storing and manipulation capacity are similar in all living things. DNA from one species can be read by another species' machinery.

DNA

DNA is made out of nucleotides. Nucleotides are made up of a base + a sugar-phosphate backbone.

DNA has a direction in which it can be read. DNA has two strands to it, connecting together, and complementing each other. A pairs with T and C with G.

Adenine + Thymine and Guanine + Cytosine

This can be used for replication. The strands split, the opposing strands get generated to match the splits and two new strands are there. This process is an instance of templated polymerization. One strand acts as the template for the other.

Forces between strands are weaker than at the backbone of a strand, hence strands can be "easily" split.

DNA needs to express its information => leading to the formation of molecules in the cell. RNAs + polymers are the results of that expression.

DNA into RNA = Transcription

RNA into Protein = Translation

RNA

RNA is a transcribed version of DNA. The backbone is from a different sugar => ribose instead of deoxyribose. And the T for Thymine is replaced with a U by Uracil. RNA is produced in bulk and discardable and can be edited and changed on the fly. DNA is fixed. RNA comes in different types. mRNA is the most widely found. messenger RNA.

RNA is flexible unlike DNA and therefore can bend back and around on itself. The shape RNA will form depends on its sequence. UUUU... would be associated with AAAA... and the two could form a bond. The specific shape can help catalyze reactions.

Proteins

Proteins give functions to cells. They can catalyze chemical reactions and form building blocks. 20 Amino Acids form the alphabet for proteins, proteins are nothing but long chains of these amino acids.

However these chains fold into complex 3D structures within cells, the structure of the protein shape is often more important than the raw sequence of amino acids. DNA is translated into amino acids 3 letters at a time. Every amino acid has a 3 letter base pair code associated with it. 64 possible codings exist, however, there are only 20 aminos, hence many codings code for the same amino acid.

The 3 letter base pair code is known as a codon. transfer RNA (tRNA) has Anticodons attached to one end and the appropriate amino acid at the other end. The assembly of amino acids from tRNAs + sequence information from mRNA happens in the ribosome. A complicated molecular machine, made from protein + ribosomal RNA.

Question: How does tRNA bind to amino acids?

Life is a set of proteins + polynucleotides (DNA, RNA) that form an "autocatalytic set" => a bunch of chemicals making more of themselves in a certain environment. Basically, cells take in food, and produce more of themselves => more protein, and more DNA.

Genes

DNA is large, coding for lots of proteins. There is certain sequences interrupting/starting new proteins. DNA segments coding for one protein => genes. DNA segments can be processed in various ways, leading to more than one distinct protein being produced from the same piece of DNA. Some DNA also doesn't code for proteins but produces RNA for other functions within the cell.

Genes are DNA segments coding for proteins, groups of proteins, or RNA snippets that do something on their own.

Not all genes are on all the time. Genes are "expressed" => turned on or off as needed by the cell. Between Genes sit stretches of regulatory DNA that don't code for anything itself. Noncoding DNA like this helps to turn on or off genes due to certain logic. Chemicals being present/not present etc.

The genome is the total information. It specifies when, how much, where, and which proteins have to be made.

Energy

A living cell is a dynamic chemical system, operating far from chemical equilibrium.

Cells need energy from the environment to survive and guide the reactions to make more polynucleotides and proteins. The order of the cell can only exist by heating up the environment more. Total entropy goes up but local entropy goes down.

ATP is necessary as an ingredient for RNA + DNA. But also used for energy.

Cells are enclosed by Plasma Membranes. Phospholipid Bilayer. Tails are hydrophobic and go inwards, and phosphate heads are hydrophilic and go outwards. Cells use this mechanism double layered to generate a closed membrane all around to maintain a constant internal environment. Embedded into this membrane are transport proteins. Structures that let through only specific molecules in one direction or the other.

The amount of genes necessary to get a working cell is surprisingly low. 400-500. Cells produce self-assembling molecules. The membrane is an example of that. So are proteins.

Most living things are microscopic.

Living things can get energy from lots of different sources and chemical reactions. Some from rocks, others from sunlight, and others from other living things. Most of life also needs specific elements => hydrogen, carbon, oxygen, nitrogen, sulfur, and phosphorus. Fixing carbon and nitrogen from the atmosphere $N_2$ and $C0_2$ compounds is hard work. Some bacteria can fix molecular nitrogen, plants can fix carbon dioxide.

The Diversity of Genomes and the Tree of Life

Life is divided into two big groups => pro and eukaryotes. Cells with or without a nucleus store DNA.

99% of procaryotes have not been cultured. But we know they exist because their DNA is present in soil and water samples.

Bacteria, Archaea and Eukaryotes are the three main branches of life.

The cycle of Trial and Error leads to Evolution. Mutations are copying errors, beneficial ones get passed on.

Different types of mutations:

• Intragenic
• Duplication
• Segment Shuffling
• Horizontal (intercellular) Transfer

Genes can be related to each other => homologs

Two different types

• related but arising from duplication => paralogs
• related but by descent => orthologs

Viruses can carry genetic information between cells by accident.

Prokaryotes can also pick up genes from their environment.

Translating between the world of genetic information and the phenotype, the actual function of a gene is hard and needs lots of good experiments.

We study model organisms a lot and E.Coli is the most studied model organism. A lot of basic knowledge about conserved genetic effects came from E.Coli. Around 200 genes are known to be conserved across all major branches of life. They mainly govern DNA replication, protein synthesis, and energy metabolism of cells.

Genetic Information in Eukaryotes

Eukaryotes are vastly more complex than prokaryotes. They have a nucleus, housing their genetic information and DNA. The nucleus is surrounded by another double-layered membrane. Eukaryotes are around 10 times bigger and have 1000 times more volume. They contain a cytoskeleton. Kind of like a delivery network that also gives structure to the cell. Probably first eukaryotes were hunter cells, using their cytoskeleton and flexible membrane to quickly change shape and thereby engulf and "eat" other cells in a process known as phagocytosis. The nucleus is a protection against the cells' own movement, so as to not damage the DNA because of it.

Eukaryotes contain mitochondria. 1.5 billion years ago a eukaryote cell swallowed another cell from the time, but instead of digesting it, co-existed with it. The symbiosis became so good, that now almost every eukaryote still has mitochondria within it. Chloroplasts are similar to Mitochondria but are found mainly in plant cells. They perform photosynthesis.

Plant cells made the transition from hunting to farming. They settled down.

Mushrooms eat dead or decaying things. Digesting them outside of their cells, also having lost the ability to rapidly move like animal cells. But not able to do photosynthesis either.

DNA from mitochondria and chloroplasts, over time, have moved into the nuclei of their respective host cells.

Eukaryotes have big genomes, where a lot of the genes don't code for proteins directly. Instead, most of the genes from eukaryotes are doing regulatory work. This leads to the ability to have profoundly different cell types, coming from the same genetic imprint.

The cell behaves as a multipurpose machine, with sensors to receive environmental signals and with highly developed abilities to call different sets of genes into action according to the sequences of signals to which the cell has been exposed.

Genes that code for proteins that regulate the transcription and translation of other genes are called transcription regulators.

The expanded genome of eukaryotes therefore not only specifies the hardware of the cell but also stores the software that controls how that hardware is used.

Cells can not only receive and react to signals, they can also send signals, controlling cells in their surroundings to do stuff they otherwise wouldn't do. In the absence of these signals, eukaryote cells can do all kinds of crazy stuff => see Michael Levin's work on Xenobots.

S. cerevisiae => Yeast serves as a model organism for Eukaryotes. It can both divide as haploid and diploid cells and can undergo sexual reproduction to switch between diploid and haploid stages of growth.

Cell division is so well conserved between organisms that yeast can function with human cell division genes when their own are disabled or deleted.

Yeast builds around 6600 proteins.

The model organism for plants is Arabidopsis thaliana. The Thale Cress. For animals there are multiple, in order of increasing complexity => nematode worm - Caenorhabditis elegans, fruit fly - Drosophila Melanogaster, zebrafish - Danio rerio, mouse - Mus musculus and human - Homo sapiens.

C. elegans has exactly 959 body cells when mature and around 21.000 proteins.

Model organisms are necessary because they develop much quicker and are overall easier to understand because of their complexity => genome and protein are much lower

Vertebrates - animals with a spine - have lots of paralogs in their genome that arose by duplication.

Mice and humans can have similar white spots on their faces due to the same mutation in the same gene. This to me is mindblowing.

Human to Human there exist 1-2 differences per 1000 nucleotide base pairs.

To Understand Cells and Organisms Will Require Mathematics,

Computers, and Quantitative Information.

Quantifying exact numbers in cellular chemical circuits is really hard, but necessary to really understand what's going on. The problem with this quantization is that most chemical circuits have feedback loops and that feedback loops are notoriously difficult to characterize mathematically since they border on chaos theory and non-linear dynamics.

Problems

1–1 Each member of the human hemoglobin gene

family, which consists of seven genes arranged in two clusters on different chromosomes, is an ortholog to all of the

other members:

– No. Because they exist all on the same species they should be paralogs and not orthologs.

1–2 Horizontal gene transfer is more prevalent in single-celled organisms than in multicellular organisms.

– No, not really, because many multicellular organisms undergo sexual reproduction, which is a form of horizontal gene transfer.

1–3 Most of the DNA sequences in a bacterial genome

code for proteins, whereas most of the DNA sequences in

the human genome do not.

– Yes. Around 98% vs. 11%.

1–4  Does the extraordinary mutation

resistance of the genetic code argue in favor of its origin as

a frozen accident or as a result of natural selection?

– I think it argues for it as a result of natural selection. Big changes in the protein code would mean that changes often break organisms and since changes happen quite often this would be very bad for the organisms and would therefore be selected against.

1 – 5 What approaches might

you try to distinguish between contamination and a

novel cellular life form based on DNA, RNA, and protein?

– I could determine whether or not they use the same molecular protein-based machinery that is conserved for almost all living things on earth. I could also see if the codon code is the same for my sample and find a place for it along the heritage of the organisms living on earth. If it fits the organisms on Earth and has an easily determinable lineage it's most likely pollution and not a "real" signal.

1 – 6 Where is the "food," for example,

in the mixture of chemicals (H2S, H2, CO, Mn+, Fe2+, Ni2+,

CH4 and NH4+) that spews from a hydrothermal vent?

– The food in this case is in the chemical energy that can be harvested from breaking the bonds between these molecules and in the chemical elements that can be harvested from the molecules themselves. H, C, O, and N can all be used to build more complex organic chemistry. And Fe2+ ions etc. can be used to catalytically move around electrons and protons to generate energy from it.

1–7 How many possible different trees (branching patterns) can in theory be drawn to display the evolution of bacteria, archaea, and eukaryotes, assuming that they all arose from a common ancestor?

– Many.

1–8 The genes for ribosomal RNA are highly conserved

(relatively few sequence changes) in all organisms on Earth; thus, they have evolved very slowly over time. Were ribosomal RNA genes "born" perfect?

– No. Ribosomal genes are really important for basic functions of life, so once fixed into place, early on, they wouldn't change much. But in the history of life until this point, where we have a hard time finding evidence for it, they must have undergone an evolutionary change as well to get better working versions.

1–9 Why would the complexity of the underlying process—informational or metabolic—have any effect on the

rate of horizontal gene transfer?

– The more complex something is, the more specific to a certain purpose it is likely adapted. That makes it harder to transfer it across species, because circumstances of use will change slightly, making the workings of the protein as intended unlikely and therefore less beneficial to actually transfer the protein.

1–10 Are fungal cells more likely to be animal cells that

gained the ability to make cell walls or plant cells that lost

their chloroplasts? How do you suppose that this question

was eventually decided?

– I think it could have been that people used the "tree of life"-style DNA analysis to determine how closely related the three groups of organisms are. If one finds out where the last common ancestor is, one can find out whether or not fungal cells are more closely related to plant or to animal cells. Basically building out a phylogenetic tree can help answer the question.

1–11

A: Does this tree support or refute the hypothesis that

the plant hemoglobins arose by horizontal gene transfer?

–  I think it refutes it. The evolutionary distance between the plant molecules and those in the different groups of other organisms is too high and it doesn't connect to the tip of one of them, which it otherwise would. Right now, the last common ancestor, the last branching point, lies outside of the horizontal gene transfer range.

B: Supposing that the plant hemoglobin genes were originally derived from a parasitic nematode, for example, what would you expect the phylogenetic tree to look like?

– That all the plant molecules connect to the tip of the nematode worms branch in the phylogenetic tree.

1–12 Can you offer one or more possible explanations

for the slower rate of evolutionary change in the human

lineage versus the rat lineage?

– Humans have fewer offspring, less often. This means that fewer mutations happen overall at the same time as happen in rats. Maybe the complexity of

Chapter 2 - Cell Chemistry and Bioenergetics

Chemistry for life is based mainly on hydrocarbons. Complex macromolecules reacting with each other form the basis for life's chemical reactions.

The Chemical Components of a Cell

C, H, N, and O make up 96.5 percent of all living things. Covalent bonds between them form molecules. Molecules are often held together by non-covalent bonds.

Bond strength is measured in kj per mole.

Water forms dipoles because O is more electronegative than H and therefore attracts electrons more strongly forming a slight negative charge on the side of the O. H's and O's can therefore form a weak bond => a hydrogen bond.

Things can dissolve in water if they are also polar. They are named hydrophilic. Things that don't form hydrogen bonds and are not polar don't mix well with water, they are hydrophobic.

Other bonds holding together chemistry in cells are ionic bonds => electrostatic attraction between charged molecules (ions), hydrogen bonds, and hydrophobic forces (some parts of molecules want to escape from the water and hence cluster together and fold into and closer to each other than to the outside) and van der Waals forces.

Macromolecules bond together because of a lot of interaction of these small forces in just the right combination of shapes. Complementary surfaces add up the small forces to overcome the energy of thermal motion and be bound semi-permanently.

Water molecules exchange protons with one another, turning into ions, on and off, all the time. When another form of proton donator or acceptor is present, the balance is tipped in one way or the other, leading to the formation of acids or bases respectively. $OH-$ (Hydroxyl ion) and $H_3O+$ (Hydronium) ions are what define acids and bases. The movement of protons between water molecules is called dissociation and association. When something releases extra protons it's an acid, more $H_3O+$ => more acidic. $10^-7$ M is the concentration of $H_3O+$ in normal water. The measurement of this concentration of $H_3O+$ ions is done in a logarithmic scale => the pH scale!

Things that readily lose their protons are strong acids. Things that readily accept protons are bases. They increase the amount of OH- ions in the solution. OH- and $H_3O+$ combine into the water again, so acids and bases cancel each other's effects on pH. They neutralize. Cells buffer their pH by having molecules that can take up or release protons near a pH of 7.

Carbons can form up to 4 bonds. Using this they can form chains, rings, lattices, and all other kinds of crazy structures. This makes them ideal to build highly complex chemicals. Organic chemistry is the study of these complex carbon-based chemicals. Some "functional groups" exist => special configurations that give certain effects to the molecule they are a part of.

Some more common ones:

methyl (–CH_3),

hydroxyl (–OH),

carboxyl (–COOH),

carbonyl (–C=O),

phosphate (–PO_3^2–),

sulfhydryl (–SH),

amino (–NH_2)

Four families of small molecules are found in cells:

fatty acids

nucleotides

amino acids

sugars

Macromolecules are what makes cells work. Small, monomeric units are linked together to form bigger, complex constructs with functionality. Molecules from the four families above are monomers and as such are the building blocks for macromolecules.

https://lh5.googleusercontent.com/fWd1rWK7nUs0FPIZCgtsTHT2F-zeHXrydXjEQMoqPcqSk265_fJXXGDEnww3_YFlcRt0JPtHIBaIvstFjPL0Uy0dOELDkjVdKiNxpSRHNvkPrXn4ZBVHcdrJCSecKDumeLqZ8EypSiBJIZt_ZkajuGFIlhqOtEKHY_p4kxxyTIv95PRGI4V5XhC5_XV_Yw

sugars => polysaccharides

fatty acids => lipids, fats, membranes

amino acids => proteins

nucleotides => nucleic acids

Proteins are made up of amino acids and work as enzymes. They make and break bonds more easily. I.e. they catalyze reactions.

Word I don't know: ribulose bisphosphate carboxylase

Word I don't know: tubulin

Organically monomers get linked into long chains by condensation reactions. Giving of water to form bonds between carbons. It can be done recursively, step by step. Monomers have to be added to the chain in the right order. Hydrolysis is the opposite reaction to condensation. Hydrolysis happens on its own because it is energetically favorable, slowly degrading macromolecules by breaking them apart again. Creating new macromolecule chains by condensation needs some energy. Therefore cells put in some energy to catalyze these reactions.

Macromolecules can rotate around many of their bonds. This means they can twist and bend into all kinds of shapes. These shapes are known as conformations. The number of possible conformations is nearly limitless, however, it gets restricted a lot by non-covalent bonds between different parts of the chain. Non-covalent bonds help drive the folding of the macromolecule into the "correct" shape.

These specific interactions of macromolecules can make them select other macromolecules. Only if something binds with the right non-covalent bonds at the right places can it get close to the macromolecule. Therefore the macromolecule can select only very specific other molecules by their chemical structure.

Living organisms are autonomous, self-propagating chemical systems.

Catalysis and the Use of Energy by Cells

One property of living things above all makes them seem almost miraculously different from nonliving matter: they create and maintain order, in a universe that is tending always to greater disorder.Cells are tiny chemical factories. Using energy to produce different products, order out of chaos.

Reactions within cells wouldn't happen on their own. They need more energy than what is normally available in the environment. They only very very rarely happen by chance. Therefore this energy has to be added by the cell. The reactions have to be catalyzed to happen. And therefore the reactions can be controlled by adding or removing the catalyst. These catalysts are usually proteins => and then we call them enzymes. Some are made out of DNA then they are called ribozymes.

Cells have 2 streams of reactions: Catabolic vs. Anabolic. Breaking down vs. building up.

Generating energy and molecules vs. using energy and moleculesTogether they form the metabolism of the cell.

Things tend to become disorderly over time because there are more ways to become disordered than there are to be ordered. Therefore, with random actions happening, disorderly things are more likely to exist over time. The more time passes, the more disorderly and random things get. They lose structure. This is known as the 2nd Law of Thermodynamics. Disorder is a spontaneous process. The amount of disorder is also known as Entropy.

However => with expanding energy, one can create more order, at least locally. The energy, however, gets dissipated as heat, making the surroundings move more quickly in random ways, increasing the disorder outside more quickly. This is the basic principle of life.

Use energy to create local order, by dissipating heat and increasing global disorder.

Life has to kinda destroy its environment to exist.

Cells release chemical energy from the bonds between molecules and convert it into the motion of other molecules => i.e. heat. Cells in a way are controlled burning. Linking the release of energy from reactions that would occur in a fire to something that is "useful" => create order by synthesizing chemical reactions that normally wouldn't happen with energy from controlled combustion.

For combustion to occur, cells need oxygen. Oxygen now comes from plants but earlier was found bound to CO_2 mostly and things split it up using chemistry and something like sunlight for a long time. Plants do a similar process to this day with photosynthesis. Plants and other organisms exist now in a closed loop, plants produce oxygen, and animals and fungi consume it thereby helping each other to exist. Without plants, animals would die and without animals, plants would die. This exchange of CO2 and O2 is also known as the carbon cycle and exists across the whole biosphere.

Oxidation and Reduction reactions exchange electrons. Oxidation is the removal of electrons. Reduction is the addition of electrons. The thing reduced is the charge of the receiving molecule, because of the added electron.

Fe2+ => Fe3+ is oxidation. Because Fe gives up an electron.

Cl => Cl- is reduction. Because Cl gains an electron.

Electrons can only shift and never be destroyed or created. Every oxidation is also a reduction of something else.

Electrons can also shift in varying degrees, not 100% and -100% only. The terms applied are still the same.

Sometimes a proton moves along with the reaction of the hydrogen so the charge stays the same, however, these are still called reducing and oxidizing reactions => Hydrogenation and Dehydrogenation respectively.

Reduction and Oxidation are easy to tell in organic chemistry. Increases in C-H bonds are reductions. Decreases are Oxidations.

https://lh4.googleusercontent.com/0cpgUSS3FeiZT-hleyOwec3Wuel8FZW2Bejsn8Tt4e2_GqQtmDcsvcxDU9j8iinjufZBCE3chE1degaQp4mpg0gMVArirhmIgB7P49rbMhUHbQV_ovAM2yqmEIKFyOhvXYCz8WEMhamCL2IZcsLThP9R6Y5nzUJ9i4gFY9OfPkWSsMXiUa009Talyj0Vuw

Chemical reactions proceed spontaneously only in the direction that leads to a loss of free energy.

Free energy is energy that is bound into the arrangement of matter and bonds and that can be used to drive reactions. Reactions only happen if they are forced or energetically favorable.

In normal conditions, H2O and CO2 are the most energetically favorable states for these atoms to organize themselves in. Not complex hydrocarbons. But cells, bodies, wood, paper, and other organic chemistry don't spontaneously self-ignite and burn away… why?

The states of these molecules are semi-stable. Like a local valley, but with a small hill that needs to be overcome to go to the much lower valley of H2O and CO2. As long as nothing pushes up the molecules up and over that hill, they don't change their state. This "hill" is known as Activation Energy.

Enzymes and other catalysts lower this activation energy by holding molecules together in just the right ways. Activation Energy can be provided by the random motion of particles. Random particles moving at sometimes higher velocities means that a certain amount of spontaneous reactions always happen. But that amount is very very low usually because only very few molecules have the speeds necessary. By decreasing that speed necessary a lot, catalysts enable a lot more reactions to happen. Sometimes by factors of 10^14 or more!

Question: Quantum Physically, WHY is activation energy needed to start a reaction? And why is it overcome if a particle moves more? And how can something that moves more bind to the enzyme without losing it's movement? Are enzymes maybe accelerating things they come into contact with?

Enzymes can't shift equilibrium points.

Question: Why exactly?

Enzymes have an active site, a special part of the protein that is shaped to only specifically bind to certain molecules.

Enzymes are not changed by the reactions they catalyze. They just let go of the non-binding substrate and try to find another thing to bind to. This only takes a fraction of a millisecond, because molecules move very fast at this scale. There are three types of thermal motion: Translation, Vibration, and Rotation. Combined these motions lead to a random walk of molecules. They diffuse outward randomly and relatively quickly. Just like a drop of ink spreads in a glass of water within seconds. This process is named diffusion. The time necessary to move is distance^2.

Enzymes move more slowly than substrates since they are bigger. So much in fact, that they can be seen as "sitting still".

Question How big are the changes in speed in reality? Does it matter that enzymes also move around?

Rates of encounter, therefore, depend only on 1 variable => substrate concentration.

Enzyme Substrate collisions are extremely frequent. About 500.000 per second with a concentration of 0.5 mM of the substrate. Dissociation of the wrong substrate happens incredibly quickly as well and once the right substrate is bound to an enzyme almost immediately after a reaction will occur.

Enzymes don't make water run uphill. They can only make the hill climb less steep. Instead cells couple energetically favorable reactions to ones that are energetically unfavorable. Using the energy released by one to make the other happen.

Free Energy G is the energy that can be used to do work. I.e. energy that is not random thermal motion. It is the opposite of entropy in a way. Things that increase entropy decrease $\Delta G$. A decrease in $\Delta G$ means a reaction is energetically favorable. Reactions that disorder the universe happen spontaneously.

Free Energy $\Delta G$ is dependent on concentration. What is more likely to happen depends on the arrangement the system is already in. There's an energetic balance at which different mixes of molecules exist at different temperatures. With changing temperature, pressure etc. the ratio of that equilibrium, where both backward and forward reactions happen at the same speed, changes. Both reactions always happen, the only thing is they happen less likely because they need more activation energy, which is randomly supplied by forceful enough collisions. If enough collisions happen => there will be some reactions anyways.

The concentration independent part of the Free Energy is more important overall. It is named Standard Free Energy Change or $\Delta G°$ and can help compare how likely reactions are independent of the concentrations.

$$\Delta G = \Delta G° + RT ln \frac{X}{Y}$$

Where X and Y are concentrations of the chemicals in the reaction. R is the gas constant and T the temperature.

We know the Standard Free Energy Change for most biochemical reactions through measurement.

$$\Delta G = 0$$

leads to chemical equilibrium. Every reaction that happens is counteracted by tipping the balance in the other direction, making the next reaction more likely to go into the other direction. A constant back and forth at the equilibrium point.

$K=\frac{a}{b}$

and then at equilibrium:

$$\Delta G° = RT ln K$$

at 37°C expressed as a log => $\Delta G° = -5.94 log K$

multiple reactants with concentrations like A + B -> C + D give the following:

$\Delta G° = -5.94 log \frac{[C][D]}{[A][B]}$

If the overall energy necessary for a reaction path is negative it can happen in cells without breaking thermodynamic laws. But the reactions with positive Free Energy have to be bound to those with negative values to happen. So that the energy released from one reaction can drive the next.

Cells don't bind every reaction of burning and breaking down food to the creation of more complex chemistry directly. Instead they use ATP or other activated carrier molecules (NADH and NADPH) that can store this energy temporarily in a readily broken bond. It's like putting energy into a useful currency so that everything in a cell can use the energy via the same "interface".

Word I don't know: Phosphoanhydride Bonds

ATP is the most widely used carrier for energy in cells. Adenosine Tri Phosphate. It looks like this and is derived from ADP by a condensation reaction.

https://lh4.googleusercontent.com/Tfp0Pam6JPj5A6ARptfcvpfQSsyErMaVGdvVGCKGhBEx2VpXAo5YqDVWYKq44yzYXgvl-zVOiqS9dnrjsUU1EAfFiTpOofZrrdiJfgKla8ZQN-nCTzewFOOGelhv790tltmfEgMlv4_-PWgkIQJvvS3lRI2AQ-0nPC5IltLWMgP0mJq2_dceP8-t6kZpiw

Hydrolisis of ATP is where most energy used for reactions in a cell comes from.

Word I don't know: Phosphoester Bond

The other activated carrier molecules like NADH and NADPH are used to carry around high energy electrons and hydrogen atoms. They also include the nonprotonated forms NAD+ and NADP+. Nicotinamide Adeninde Dinucleotide (Phosphate). They can pick up two electrons and a H+ proton and are then their reduced forms. NADH and NADPH respectively. They carry Hydride Ions => H-. Hydrogen + an extra electron.

NADH and NADPH are very similar in the way the carry around Hydride ions. But they can bind to different sets of molecules because of their different shapes due to the extra phosphate. Why are two different carriers needed? Because NADPH plays a role in anabolism, whereas NADH plays a role in catabolism instead. Having separate control over both is beneficial to cells.

Word I don't know: Acetate

Word I don't know: Nicotinamide

Word I don't know: Coenzyme A

Word I don't know: Acetyl CoA

Word I don't know: Thioester Linkage

Word I don't know: Acetyl Group

Word I don't know: Reduced Flavin Adenine Dinucleotide (FADH2)

Word I don't know: Adenosylmethionine

Word I don't know: Carboxyl Group

Word I don't know: Uridine

ATP => phosphate. NADPH => electrons and hydrogen. Acetyl CoA => two carbon units. I.e an acetyl group

FADH2 => electron and protons

Carboxylated biotin => Carboxyl group

S-Adenosylmethionine => Methyl group

Uridine diphosphate glucose => Glucose

Polymers are created by condensation and broken apart by hydrolisis. Removing and adding of water.

Word I don't know: Pyruvate

Word I don't know: Pyruvate Carboxylase

Word I don't know: Biotin

Word I don't know: Oxaloacetate

The energy released by ATP to ADP hydrolisis is around -54 kJ/Mol and can drive reactions with $\Delta G$ Free Energy of up to around +40 kj/Mol. Some reactions in cells need more free energy than that. There is other pathways involving AMP (adenosine mono phosphate) and pyrophosphate that can give a boost for up to -100 kj/Mol. Polynucleotides are synthesized that way.

Word I don't know: Pyrophosphate

Polymerization of a chain can occur from two ends. Head Polymerization vs. Tail Polymerization.

In head polymerization end needs to carry a high energy bond for the next link to bind onto. Examples are proteins and fatty acids.

In tail polymerization the link get's used up immediately when binding. Monomers carry the bond necessary to do their own binding. Examples are DNA, RNA and Polysaccharides.

The energy needed for life comes ultimately from the electromagnetic radiation of the sun, which drives the formation of organic molecules in photosynthetic organisms such as green plants

How Cells Obtain Energy from Food

Sugars are oxidized step by step to produce ATP or other activated carryer molecules. The most common process for this is called Glycolisis. To rupture sweet stuff. Glycolisis doesn't need O2. It produces pyruvate as it's final product. In animals and other aerobic organisms this get's further oxidizied to CO2 + acetyl CoA and eventually to CO2 + H2O.

Glycolisis:

https://lh6.googleusercontent.com/0zJcL_q39i-nFBPP-P-AX219LOoc1w8Tpj4YdkWguhWiKQEVEw9Y_Yh8rI-A_FFClehGOtwqNr0876ixKqYhGOuyqbuXlvexZdOmoLOMdoTAn82vUO2PGn7RuHh9yWm1F3S3oOggRwL35kw6l8yC6h8ax89ebM7hUNQBoUjZK1z0-J71bnJDF7Cnt-oU8g

Stepwise "burning" of sugars is the key to life's energy. Each step yields a little bit of energy, captured in a form (ATP, NADH etc.) that is useful to the cell to drive other reactions.

In anaerobic conditions the pyruvate gets further processed and then excreeted from the cell. In yeast for example as alcohol, in the muscle in the absence of oxygen as lactate. This is necessary to regenerate NAD+ from it's reduced form NADH.

When organic molecules both accept and donate electrons to produce energy the reaction pathway is called a fermentation. Fermentations are often anaerobic, without oxygen.

Word I don't know: Acetaldehyde

Word I don't know: Glyceraldehyde 3-phosphate

Word I don't know: Aldehyde

Word I don't know: Phosphoglycerate

Word I don't know: Carboxylic Acid

Cells store their energy not in ATP but in the precursors necessary to generate ATP via oxidation of sugars. They use either fats or glycogen for that. Fats are usually stored as triacylglycerols => triglycerides in specialized cells named adipocytes. Sugars like glucose are stored as glycogen or starch in plants. Storing energy in fats is more efficient in weight. That's why animals primarily use fats for longer term storage and sugars for shorter term storage. That's because water is included in the generation of the sugar polysaccharides and this water adds up the more sugar is stored. However, sugar is more easily available for energy generation in the cell so it's preferred.

Glycogen phosphorylase splits sugars out of Glycogen and adds a phosphate group to feed it the sugar into glycolisis, yielding glucose 1-phosphate which is then turned into glucose 6-phosphate before undergoing glycolisis.

Plants have mitochondria and export sugar from photosynthesis out of chloroplasts to the mitochondria to produce ATP there by glycolisis and further oxidation. This ATP is then exported to the rest of the cell. Plant seeds are rich in fats and sugars for storage until the plant germinates.

Word I don't know: Pyruvate dehydrogenase complex

Word I don't know: Serum Albumin

Citric acid cycle is fed with acetyl CoA and turns it's acetyl group into H2O and CO2 while producing lots of ATP. It happens in mitochondria and needs molecular oxygen O2.

Fatty acids can be turned into acetyl CoA and therefore also be used to drive the citric acid cycle. This is a recursive process, where the fatty acid is capped for carbon atoms at it's tail. Producing acetyl CoA, NADH and FADH2 in the process. It happens in mitochondria. It's named Fatty Acid Oxydation Cycle.

Amino acids can also be turned into acetyl CoA or other intermediate steps of the citric acid cycle, which means that all three fats, proteins and sugars can drive ATP synthesis in eukaryotic cells.

Technically it's not the Citric Acid Cycle that needs O2 but the restoration of NADH into NAD+ => this is also what produces the water and most of the ATP and it happens at the electron transport chain also known as ETC. This is a topic of a later chapter as well. The process going on there is called oxidative phosphorylation or OxPhos.

Citric Acid Cycle also known as Krebs Cycle or as Tricarboxylic Acid Cycle is the main way for aerobic cells to generate NADH to feed into the ETC and therefore a necessary part of the ATP production of aerobic cells.

acetyl CoA transfers it's acetyl group onto oxaloacetate forming => tricarboxylic acid also known as citric acid. 6 carbon long. Eight reactions happen, by the end of which, oxaloacetate comes out again + three NADH, one GTP, one FADH2 and two CO2. GTP is a ribonucleoside triphosphate. Very similar to ATP. Basically exchanged the base adenosine by Guanosine et. voila.

Word I don't know: GTP - Guanosine Triphosphate

Word I don't know: α-ketoglutarate

Workings of the ETC, the electron transport chain. ETC is made up of special electron acceptor, donor molecules. Electrons get transferred to lower and lower energy states, while with each transfer H+ protons get pumped across the mitochondrial membrane from inside to outside to build up charge that can be harvested for chemical work later on. Mostly for ATP synthesis by phosporylation of ADP. Complete oxidative phosphorylation ⇒ oxphos generates 30 ATP's. Glycolisis only does 2.

Not only carbon is cycled in and around cells, so are Nitrogen and Sulfur. Nitrogen is limited in nature, it is abundant in the atmosphere but in a mostly unusable form of N2. Only few organisms can fix this nitrogen from the atmosphere. Lightning strikes also fix nitrogen. The total amount of nitrogen usable for organisms forms a closed loop cycle.

Word I don't know: Sulfate

Word I don't know: Sulfide

Word I don't know: Sulfites

Organisms can not use Sulfate (SO4^2-), the most common form of Sulphur atoms in nature. Instead they nead Sulfide (S^2-) ions.

Essential Amino Acids that need to be taken in via diet:

• THREONINE
• METHIONINE
• LYSINE
• VALINE
• LEUCINE
• ISOLEUCINE
• HISTIDINE
• PHENYLALANINE
• TRYPTOPHAN

Complexity of biochemical pathways. In red is the Krebs Cycle.

Cells produce a lot of different compounds in a lot of different ways, in a highly complicated chemical dance. Furthermore, different cell types, synthesize different, and sometimes specialized chemicals, turning on different pathways not even shown in the above diagram, to produce such things as hormones or antibodies.

All of these pathways are elaborately controlled, meaning that cells can react to changes in their environment and even mutations in those pathways quite adeptly. They are robust, yet complex.

The main metabolism of the Cell: Glycolisis ⇒ Citric Acid Cycle ⇒ Oxidative Phosphorylation

Turning sugars into ATP.

Problems

2 – 1 A 10^–8 M solution of HCl has a pH of 8. – Can't be true. Because HCl is acidic it shouldn't increase the pH above 7 but only below.

2–2 Most of the interactions between macromolecules could be mediated just as well by covalent bonds as by noncovalent bonds. – Not true. Covalent bonds would be too strong and permanent to allow for the rapid association and dissacociation necessary for most enzyme – substrate reactions. Things would come to a halt since a protein wouldn't let go of it's catalyzed substrate anymore. Also the specificity of covalent bonds in combination with macro-molecules would make it a lot harder to even bind in the first place. Especially since activation energies would have to be overcome to form these strong bonds as well.

2–3 Animals and plants use oxidation to extract energy from food molecules. – Technically not true, since plants manufacture their own food molecules, in which case it can't really considered food anymore. However true in so much as that both use oxygen and oxidation to break down sugars and fats and convert them into usable energy in the form of ATP.

2–4 If an oxidation occurs in a reaction, it must be accompanied by a reduction. – True, otherwise where does the electron go?

2–5 Linking the energetically unfavorable reaction A → B to a second, favorable reaction B → C will shift the equilibrium constant for the first reaction – Not true. It will only shift the likelyhood of the reaction happening at all. However removing B continously from the products will shift continously let the reaction of A to B happen. Producing overall more B than what otherwise would have been produced. However, in the end, once B ⇒ C are in equilibrium, so will A to B come to equilibrium.

2–6 The criterion for whether a reaction proceeds spontaneously is ΔG not ΔG°, because ΔG takes into account the concentrations of the substrates and products. – True. But ΔG° is better for comparing different reactions with each other.

2–7 The oxygen consumed during the oxidation of glucose in animal cells is returned as CO2 to the atmosphere. – Not entirely true. Some of it is bound up in water as well.

2–8 The organic chemistry of living cells is said to be special for two reasons: it occurs in an aqueous environment and it accomplishes some very complex reactions. But do you suppose it is really all that much different from the organic chemistry carried out in the top laboratories in the world? Why or why not?

– True. No lab in the world carries out organic chemistry at the scale and complexity of living organisms yet. The amount of enzymes and complexity still not understood in cells shows that this is the case. Also the organic chemistry going on in labs is not capable of producing sentient life-forms yet. The side effects generated by organic chemistry in cells – i.e. living, reproducing, constantly dividing and changing selfs, are something still to be attained, by even the top laboratories in the world.

2–9 The molecular weight of ethanol (CH3CH2OH) is 46 and its density is 0.789 g/cm3. A. What is the molarity of ethanol in beer that is 5% ethanol by volume? [Alcohol content of beer varies from about 4% (lite beer) to 8% (stout beer).] B. The legal limit for a driver's blood alcohol content varies, but 80 mg of ethanol per 100 mL of blood (usually referred to as a blood alcohol level of 0.08) is typical. What is the molarity of ethanol in a person at this legal limit? C. How many 12-oz (355-mL) bottles of 5% beer could a 70-kg person drink and remain under the legal limit? A 70-kg person contains about 40 liters of water. Ignore the metabolism of ethanol, and assume that the water content of the person remains constant.

D. Ethanol is metabolized at a constant rate of about 120 mg per hour per kg body weight, regardless of its concentration. If a 70-kg person were at twice the legal limit (160 mg/100 mL), how long would it take for their blood alcohol level to fall below the legal limit?

2–10 A histidine side chain is known to play an important role in the catalytic mechanism of an enzyme; however, it is not clear whether histidine is required in its protonated (charged) or unprotonated (uncharged) state. To answer this question you measure enzyme activity over a range of pH, with the results shown in Figure Q2–1. Which form of histidine is required for enzyme activity? 2–11 The three molecules in Figure Q2–2 contain the seven most common reactive groups in biology. Most molecules in the cell are built from these functional groups. Indicate and name the functional groups in these molecules. 2–12 "Diffusion" sounds slow—and over everyday distances it is—but on the scale of a cell it is very fast. The average instantaneous velocity of a particle in solution—that is, the velocity between the very frequent collisions—is: v = (kT/m)½, where k = 1.38 × 10–16 g cm2/K sec2, T = temperature in K (37°C is 310 K), and m = mass in g/molecule. Calculate the instantaneous velocity of a water molecule (molecular mass = 18 daltons), a glucose molecule (molecular mass = 180 daltons), and a myoglobin molecule (molecular mass = 15,000 daltons) at 37°C. Just for fun, convert these numbers into kilometers/hour. Before you do any calculations, try to guess whether the molecules are moving at a slow crawl (less than 1 km/hr), an easy walk (5 km/hr), or a record-setting sprint (40 km/hr). 2–13 Polymerization of tubulin subunits into microtubules occurs with an increase in the orderliness of the subunits. Yet tubulin polymerization occurs with an increase in entropy (decrease in order). How can that be?

– The surrounding gets more disorganized because in the polymeraztion the surrounding heats up. This stray energy in the form of heat means that the total, global entropy still increases, even though it increases locally. The increase outside is bigger than the decrease inside.

2–14 A 70-kg adult human (154 lb) could meet his or her entire energy needs for one day by eating 3 moles of glucose (540 g). (We do not recommend this.) Each molecule of glucose generates 30 molecules of ATP when it is oxidized to CO2. The concentration of ATP is maintained in cells at about 2 mM, and a 70-kg adult has about 25 liters of intracellular fluid. Given that the ATP concentration remains constant in cells, calculate how many times per day, on average, each ATP molecule in the body is hydrolyzed and resynthesized. 2–15 Assuming that there are 5 × 1013 cells in the human body and that ATP is turning over at a rate of 109 ATP molecules per minute in each cell, how many watts is the human body consuming? (A watt is a joule per second.) Assume that hydrolysis of ATP yields 50 kJ/mole. 2–16 Does a Snickers™ candy bar (65 g, 1360 kJ) provide enough energy to climb from Zermatt (elevation 1660 m) to the top of the Matterhorn (4478 m, Figure Q2–3), or might you need to stop at Hörnli Hut (3260 m) to eat another one? Imagine that you and your gear have a mass of 75 kg, and that all of your work is done against gravity (that is, you are just climbing straight up). Remember from your introductory physics course that work (J) = mass (kg) × g (m/sec2) × height gained (m) where g is acceleration due to gravity (9.8 m/sec2). One joule is 1 kg m2/sec2. What assumptions made here will greatly underestimate how much candy you need? 2–17 In the absence of oxygen, cells consume glucose at a high, steady rate. When oxygen is added, glucose consumption drops precipitously and is then maintained at the lower rate. Why is glucose consumed at a high rate in the absence of oxygen and at a low rate in its presence?

Water forms "flickering clusters", joining to the polar ends of other water molecules.