Microorganisms and Disease Lecture Slides PDF

Microorganisms and Disease Class 02, Jan 23, 2025 Micro Universe and Impacts Reading: Chapter 1-intro, 1.1, 1.2, & 1.3 Note that unannotated Figures in these powerpoint presentations are derived from Nester’s Microbiology, © McGraw Hill (course Textbook), with permission Announcements Pre-class q...

Microorganisms and Disease Class 02, Jan 23, 2025 Micro Universe and Impacts Reading: Chapter 1-intro, 1.1, 1.2, & 1.3 Note that unannotated Figures in these powerpoint presentations are derived from Nester’s Microbiology, © McGraw Hill (course Textbook), with permission Announcements Pre-class quiz for Class 01 is still open (until next Thursday). Pre-class quiz for today is closed – 30 people missed! In-Class Assessment 01 – graded. If questions, see me. HW for Class 01 is a special case – due Week from today! ➔ must be in person to me in my office! HW for Class 02 available after today’s class, due Sunday Pre-quiz for Class 03 open after today’s class 13 4 1/23/25 Review Syllabus states class policies and rules Some key elements Regular assignments for each class: quiz, in-class, HW Five exams on fixed schedule No late work No “make up” work No “extra credit” work Encouraged to talk to professor – email or in person, any topic Today’s Agenda: Stories and “what to memorize” Philosophy of Evidence and Rules Historical Example(s) Microorganism learning Microorganism examples – first pass 25 6 1/23/25 AB Some “ Yes” or “No” Questions Can Micro-Organisms [MOs] Learn and Remember? Can MOs make decisions based on data? Do MOs have a brain? IF we accept Mos do not have a brain, but do Learn and remember, where do they store the information and how do they retrieve it? Más sabe el diablo por viejo que por diablo Paraphrased: The devil knows more by being old than by being a devil. And Bacteria and Archaea are very old… 37 8 1/23/25 Information Stored in Nucleic Acids (DNA or RNA) MO Instruction and Grading are tougher than any course you’ve taken. Given a situation – you have to guess. If you guess wrong, you die. If you guess right, live, and reproduce -- Not only do you remember, but so do your offspring. Very slow process, and a lot of dead ends (literally!) But the time scale we are looking at is hard to imagine. Each Micro-Organism has Memorized (written in DNA) 3.8 Billion Years of experience In this class we have 13 weeks… What do you expect to learn? And how will you learn it? 49 10 1/23/25 What is Learning? DNA of every cell alive today contains almost 4 billion years of memory of trial and error. Hard wired learning on day-to-day survival, growth, and reproduction. Response to stimuli. Other innate learning includes response to stimuli or learned behaviors. Some animals can learn new behaviors that have short term positive feedback. Some can even be seen teaching others by example We do all those things Trial and Error Immediate rewards Memorize examples. But we are capable of so much more. 51/23/25 ”What?” is not enough We have a need for “Why?” 11 We need a story…. Humankind has long recognized infectious diseases as responsible for Illness and even death not related to physical injury and distinct from effect of poisons – but not knowing why, they invented reasons. In the book of Deuteronomy 23:12-14 we find explicit instructions for camp sanitation, requiring burial of human excrement outside of the camp. With no concept of infectious agents, the justification provided was that God walks through the camp at night, and we wouldn’t want his shoes to get dirty! In many cases, the diagnosis of the disease was remarkably accurate, but without knowledge of MOs, etiology explanations were haphazard. Roman medicine included accurate descriptions of periodic fevers, but the only cause they could imagine was the poison of the “bad air” [“mal” “aria”] associated with swamps → calling the disease malaria! 12 613 14 1/23/25 Trying to memorize everything in this course is poor strategy… You only “learn” what told. If you forget any item, it is gone… But if you understand the story… You still know what you remember You can interpolate to fill holes in your memory. And you also can predict and extrapolate to new circumstances 71/23/25 In the Stories of Science, the focus is on …. Understanding Why? About extrapolating and predicting About rules and principles → but only if the story is correct! ➔ and self correcting! 15 Scientific Stories Are Continually being Refined! I will frequently cite general rules and principles that reflect the level of understanding I think appropriate for an introductory course in Microbiology. For example: Information only flows from DNA → RNA → Protein Or, There are only four RNA BASES → A,G,C, & U Know that every rule has exceptions For scientists, understanding the exceptions actually strengthens the utility of the rule. For this course, focus will be on the general, sometimes simplistic rule – with important exceptions noted! If you want to better explore exceptions or refining of rules, that would be a good topic for office hours. FOCUS ON UNDERSTANDING THE STORY 16 817 18 1/23/25 Where do Stories Come From? People view the world through different lenses, including Art, Science, Philosophy, Religion, Politics, Law, or other personal bias. Each viewpoint has its own standard for evidence or measures of success, and they can give very different goals or valuations that are not always reconcilable. For Science, the stories have specific requirements, often summarized as the “Scientific Method” Based on observations and data. Makes predictions that are testable. Predicted outcomes are continually tested by the community If exceptions are found, the story is revised and communicated to the community. And the cycle continues. The Story of Infectious Diseases Humankind has long recognized infectious diseases as responsible for Illness and even death not related to physical injury and distinct from effect of poisons Working theories of the day credited the unseen spirits or gods or magic or evil and the like. Then, in 1674, some of the unseen became seen… 919 20 1/23/25 The Birth of Microbiology Late 17th century, a Dutchman, Antonie van Leeuwenhoek, and an Englishman, Robert Hooke, independently created powerful magnifying devises and showed that there was a world of creatures so small that they could not be seen by the unaided eye. This did not immediately change the concept of disease, but it set the stage for change. Death of Theory of Spontaneous Generation Late 19th century (200 years later), Louis Pasteur showed that spoilage of grape juice could be prevented by boiling the juice and the blocking access of microorganisms to the juice. → Proposed the hypothesis that life can only arise from life! Other experimenters disputed the generality of the claim, showing that some media (hay infusion broth) would grow organisms after boiling, even in isolation! (Exceptions!) Finally, John Tyndall showed that the exceptions were due to heat resistant bacteria (we will talk about endospores, later!) – which still supported that “all life comes from life.” Took years for this story to fully develop! 1021 22 1/23/25 Birth of Story of Infectious Disease Still in the 19th century, Louis Pasteur and Robert Koch independently demonstrated that some diseases are due to infectious microorganisms Going back to dirty shoes and bad air – Public health and sanitation grew from an understanding of the role of fecal material in transmission of disease organisms. The “bad air” of the swamps was shown to be a matter of infected mosquitoes living in the swamps and flying through the air. Set off a bonanza of research into identifying the infectious agents of all diseases. Still ongoing. “Round up all the usual suspects!” Cellular life forms Bacteria Archaea How many of you knew about Archaea before this week’s reading? And how many of you who knew could spell it correctly without first looking it up? Eukaryotes Single celled – like Protists, Fungi, Multi-cellular – like helminths Other infective agents Viruses Viroids Prions 1123 24 1/23/25 Who are these ”Infectious Agents” Cellular Agents Visible (barely, in some cases) by light microscopy Originally classified into two broad groups Eukaryotes (true nucleus) And Prokaryotes (no nucleus) Special stains subdivided even further DNA analysis of shared genes (ribosomal genes) that caused us to rethink the world! Universal Tree Assesses the accumulation of mutations in DNA Lengths of lines correlate with evolutionary time Simplest assembly – all cellular life evolved from one single-celled ancestor Geological timeline Earth is ca. 4.6 billion years old Life started 3.5 – 3.8 billion years ago By 2.5 million years ago, single celled organisms were terraforming the planet, adding oxygen to the atmosphere. Spread and evolved to fit essentially every habitable zone on the planet. 12Universal Tree of Cellular Life Access the text alternative for slide im ages. © McGraw Hill LLC 25 Cellular Life Arose One Time And evolved to fit into every livable corner of the Earth. NSF estimates 1,000,000,000,000 different bacteria species on earth, 99.999% of which are not yet discovered! And only a handful cause disease in humans… We are just another environmental niche they may want to colonize… And we are back to learning by trial and error, and being very old: (Más sabe el diablo por viejo que por diablo.) – evolving to live and grow in different environments. 26 1/23/25 25 1327 28 1/23/25 With the discovery of a micro universe, people began to understand. Microorganisms can cause disease, but our disease and suffering is not their intent. Their billions of years of evolution have focused on surviving, growing, and reproducing. If they did want to kill us, we would be dead by now. Understand that these tiny things terraformed a planet! If we can understand their specific needs, we can manipulate their activities to our benefit, to control infections, preserve foods, and stimulate good health. We are finding more cases where MOs even have a commensal relationship with us – with us supporting their growth and reproduction and them protecting us for other MOs! Generalizations about Human Infectious Diseases Microbes are not trying to kill us! We are just another potential environmental niche. Some Microbes that have interacted with Humans over generations and evolved to a kind of balance – whether symbiotic or parasitic, both organisms survive to reproduce and evolve! Other microbes had/have some characteristic, evolved for other environments, that happens to cause severe disease. 1429 30 1/23/25 Remember how MOs “Learn”? If MO kills too quickly, no growth/transmission. (Ebola) →No advantage → No learning. Continual short-term issue. If MO is quickly killed by host, no growth/transmission. (Tetnus) →No advantage →No learning. Continual short-term issue. But in some microbes (and some humans) can allow for evolution... MO and host can learn! Evolving into a kind of balance. Still can be a crappy deal for the patient... Emerging Infectious Diseases Accidental crossover (e.g., zoonosis) E. coli O104:H4 Ebola HIV-1 COVID-19 Climate change exacerbated Lyme disease Chagas disease Malaria Societal exacerbation Drug resistance (e.g., Tuberculosis, Staph.) Rapid world-wide travel/connections. Unequal access to medical care and treatments. Misinformation preventing application of medical care and treatments. 151/23/25 Last Point (for now) on Universal Tree of Cellular Life Access the text alternative for slide im ages. © McGraw Hill LLC 31 31 A Quick Check: Which emerging infectious diseases is least likely to evolve into a balance with humans? (A). COVID-19, respiratory infection that was epidemic and rapidly evolving (B). Clostridium perfringens, a wound infection that causes gas B gangrene and rapidly kills the host unless all infected tissue is amputated. (C). Ebola – an extremely contagious hemorrhagic virus that rapidly kills most infected humans. (D). Chickenpox virus – infecting children with a rash, but also reemerging as “shingles” in older adults? C D 32 1633 34 1/23/25 MOs don’t even have to infect us to impact us! The great famine in Ireland in the 1800s was largely due to a microbial disease of potatoes A bacterial disease that kills olive trees, first seen in southern Italy in 2013, has spread to Spain and France, contributing to a recent worldwide drop in olive oil production A fungal disease called “wheat blast” devastated wheat crops in South America, then spread to Bangladesh in 2016, resulting in the loss of over 35,000 acres of crops that year. Two years later it was found in Zambia Frog populations around the world have been decimated by a fungal disease called chytridiomycosis Not just impacting frog-leg diners – think insect control! Back to Infectious Disease Focus Most microorganisms are not harmful – some are even beneficial Those that cause disease are called pathogens. They can cause disease by Directly damaging body cells and tissues. Creating toxins that damage cells and tissues. Releasing waste products (from MO growth) that damage cells and tissues. Stimulating the body’s defense mechanisms, resulting in collateral damage. 1735 36 1/23/25 Their impact can far exceed anything we have done to ourselves (so far) Influenza in 1918 to 1919 killed more Americans than died in WWI, WWII, and the Korean, Vietnam, and Iraq wars combined The COVID-19 pandemic has resulted in the death of more than 15 million people worldwide, including over 1 million Americans Some specific successes (but...) Smallpox eradicated! The disease once killed one-third of its victims; left others blind or scarred Devastated unexposed populations, such as native inhabitants of Americas World-Wide vaccination program – can tell you stories of real heroes! No reported cases since 1977, but laboratory stocks of virus remain And Monkey pox is emerging... Plague deaths less than 100 per year Killed one-third of population of Europe (approximately 25 million people) between 1347 and 1351 Control of rodent populations and human respiratory secretions to prevent spread Antibiotics for treatment But we still have plague throughout the southwest region, just not human spread! Polio nearly eliminated by vaccination Emphasis on “nearly”. Eliminating the last human reservoirs stymied by religion and politics. Measles also “nearly” in US. Don’t get me started... 1837 38 1/23/25 Cellular Infectious Agents – “Usual Suspects” All living cells can be classified into the three domains we saw earlier. Bacteria Archaea Eukarya All three domains include known or suspected pathogens (Archaea sidebar and optional reference) ” A rose by any other name....” Quick sidebar on Binomial System of Nomenclature Generally two words Genus (capitalized) species name (not capitalized) Both genus and species are either italicized or underlined Genus may be abbreviated (E. coli) if clear from context But note Escherichia coli and Entamoeba coli are both E. coli! Also, can use ‘spp.’ for multiple species: Plasmodium spp. 1939 40 More on Scientific Names Name often reflects characteristic of organism or honors a scientist who worked with the organism. Escherichia (honors Theodor Escherich) coli (indicates the colon, where these bacteria often live) Members of a species with important minor differences may be indicated with a strain designation (E. coli K12) Informal names that resemble genus names are not italicized Members of the genus Staphylococcus are often called staphylococci © McGraw Hill LLC Members of the Microbial World—Table 1.1 Table 1.1 Characteristics of Members of the Three Domains Characteristic Bacteria Archaea Eukarya Cell type Prokaryotic Prokaryotic Eukaryotic Number of cells Unicellular Unicellular Unicellular or multicellular Membrane-bound organelles No No Yes Ribosomal RNA sequences unique to the group Yes Yes Yes Peptidoglycan in cell wall Yes No No Typical size range 0.3–2 μm 0.3–2 μm 5–50 μm © McGraw Hill LLC 1/23/25 39 40 2041 42 1/23/25 Bacteria Single-celled prokaryotes Most have a Rigid cell wall containing ‘peptidoglycan’ (polymer that is unique to bacteria) Many move using one or more ‘flagella’ Multiply via binary fission Obtain energy from a wide variety of sources; some are photosynthetic Most species have a consistent, specific shape. Names can derive from bacteria or cluster shapes... Recognize, don’t memorize… Coccus (plural: cocci) -- Spherical cells, Bacillus (plural: bacilli) -- A rod shaped, cylindrical cell) Vibrio (plural: vibrios) -- A short, curved rod Spirochete (plural: spirochetes) -- A long, spiral-shaped cell with a flexible cell wall Cocci that remain as pairs are called diplococci Bacteria that form long chains – Streptococcus (strepto means “twisted chain”) Cocci that form grape-like clusters -- staphylo means “bunch of grapes” Archaea -- to date, minor player in human 21 disease Single-celled prokaryotes similar in size, shape, and properties to bacteria Major differences from Bacteria in chemical composition Cell walls lack peptidoglycan Ribosomal RNA sequences different To date, most research is on “extremophiles” High salt concentration, temperature Many are common in moderate environments Also found in human microbiomes (intestine, oral cavity) See optional (i.e., not on exam) article from CDC, this year. 43 Eukarya Eukarya: single-celled or multicellular eukaryotes Eukaryotes studied by microbiologists include fungi, algae, protozoa, and helminths (worms) Algae and protozoa also referred to as protists Table 1.3 Eukaryotic Organisms Studied by Microbiologists Organism Characteristics Fungi Use organic material for energy. Size range from microscopic (yeasts) to macroscopic (molds; mushrooms) are the reproductive structures of some fungi. Algae Use sunlight for energy. Size range from microscopic (single- celled algae) to macroscopic (multicellular algae). Protozoa Use organic material for energy. Single-celled microscopic organisms. Helminths Use organic material for energy. Adult worms are typically macroscopic and often quite large, but their eggs and larval forms are microscopic. © McGraw Hill LLC 44 1/23/25 44 2245 46 Fungi Fungi: diverse group ranging from single- celled yeasts to multicellular filamentous molds The microscopic filaments of molds, called hyphae, form a visible mat called a mycelium Filamentous molds spread by release of microscopic spores (conidia) Mushroom: macroscopic reproductive structure characteristic of some fungi Secrete enzymes onto organic materials, and then take in the released nutrients Opportunistic infections (e.g., yeast) Also, systemic infections on skin and in lungs. Janice Haney Carr/CDC Access the text alternative for slide im ages. © McGraw Hill LLC Algae Diverse group of photosynthetic eukaryotes Single-celled or multicellular Photosynthesis in algae occurs in chloroplasts which contain chlorophyll or other pigments that give characteristic colors Usually live near surface of water or in moist habitat Rigid cell walls and flagella distinct from those of prokaryotes Only rarely a pathogen, but some species secrete toxins into water. (Note: Cyanobacter are bacteria, NOT algae) Lisa Burgess/McGraw Hill © McGraw Hill LLC 1/23/25 45 46 2347 48 Protozoa Diverse group of single-celled eukaryotes Complex, larger than prokaryotes Most ingest organic compounds No rigid cell wall Most are motile Energy from ingested organic material Pathogenic protozoa are often included under the term Parasites. Melba Photo Agency/Alamy Stock Photo © McGraw Hill LLC Helminths Parasitic helminths are worms that live at the expense of a host Adult worms of most species can be seen with the naked eye. However, these stages are often embedded within the body and not easily viewed. The diagnostic stages (larvae and ova (or eggs) usually require use of a microscope – hence their inclusion under Microbiology. Helminths include roundworms (Ascaris), tapeworms (Taenia), and flukes © McGraw Hill LLC 1/23/25 47 48 2449 50 1/23/25 Acellular Infectious Agents As name implies – they are not cells → Not on the universal tree of life Unlike cells, they have originated many times They are the lawyers of the Microbiology Universe They take perfectly reasonable laws and rules  Then twist them beyond recognition for their own benefit. Top category are Viruses! Quick Check: Are Viruses living entities? (A). They cannot reproduce on their own. Obviously, they are not alive. A B (B). Even though they need help to replicate, they can evolve evolve independently of the host. Obviously, they are alive. 2551 52 1/23/25 Quick Check: Are Viruses living entities? (A). They cannot reproduce on their own. Obviously, they are not alive. A B (B). Even though they need help to replicate, they can evolve evolve independently of the host. Obviously, they are alive C (C). I don’t know if they are alive or dead, but most of the time I want to kill them... Another Group: Acellular Infectious Agents As name implies – they are not cells → Not on the universal tree of life Unlike cells, they have originated many times They are the lawyers of the Microbiology Universe They start perfectly reasonable laws and rules Then twist them beyond recognition for their own benefit. Not clear if they are alive (depends on definitions) but they all learn in the same evolutionary classroom as cells And two of them use the same nucleic acid memory. By definition, they are all pathogenic to something! 2653 54 Acellular Infectious Agents—Table 1.4 Agent Characteristic Viruses Consist of either DNA or RNA, surrounded by a protein coat. Obligate intracellular agents that use the machinery and nutrients of host cells to replicate. Viroids Consist only of RNA; no protein coat. Obligate intracellular agents that use the machinery and nutrients of host cells to replicate. Prions Consist only of protein; no DNA or RNA. Misfolded versions of normal cellular proteins that cause the normal versions to misfold. © McGraw Hill LLC Viruses Nucleic acid packaged in protein coat Infect living cells, referred to as hosts Obligate intracellular agents Multiply using host cell machinery and nutrients Inactive outside of host All forms of life can be infected by different types May kill host cell May remain within host cell and replicate viral genetic information as host cell multiplies Fun fact – your genome is carrying thousands of viral genomes (ca 8% of your DNA). Fortunately, most of them have been enjoying a free ride for so long they have forgotten how to get out, replicate, and kill us.... Cynthia S. Goldsmith and Thomas Rowe/CDC © McGraw Hill LLC 1/23/25 53 54 2755 56 Viroids Consist only of a single short piece of RNA (They generally need a buddy to get them into the plant in the first place) Obligate intracellular agents Cause a number of plant diseases To date, only one known human disease – Hepatitis D © McGraw Hill LLC Prions (aka “slow viruses”) Infectious proteins: misfolded versions of normal cellular proteins found in the brain Misfolded version in contact with normal version causes the normal protein to also misfold! Abnormal proteins form fibrils and aggregates Cells die leaving spaces in brain (spongiform encephalopathy) Resistant to usual sterilization procedures EM Unit, VLA/Science Source © McGraw Hill LLC 1/23/25 55 56 2857 58 1/23/25 If time – Scientific Method and information transfer 1900s – was “obvious” that proteins were the only molecule sufficiently complex to transfer information. Carbohydrates were polymers of sugar, for energy. DNA was polymer of nucleic acids for nitrogen storage. 1930-1944, Avery, MacLeod, & McCarty claimed that DNA was actually the transmitting molecule. Long, drawn out fight. Final nail in coffin was Watson & Crick (& ) showing how DNA replicated information. 1970-1988, Pruisner claimed that protein, alone could carry the information to cause disease. Same long, drawn arguments as before, but with roles reversed. There are exceptions to every rule – whatever the rule is. And the Scientific Method will (eventually) sort it out! Finish overview Stories vs memorization Scientific Method Rules and philosophy Disease Usual Suspects 291/23/25 Class 03 Molecules of Life, pt I Jan 28, 2025 Reading Ch 2-Intro, 2.2, 2.3, & 2.4a Announcements Class 1 In-Class still running – get to my office during office hours! Class 2 and Class 1 HWs and quizzes are completed Practice exam is posted – try out your laptop/ipad! 13 4 1/20/25 Recap – Have been introduced to Scientific Method Stories and Rules Scientific Method to develop and revise stories. Usual Suspects for Infectious Disease Bacteria Archaea Eukarya Viruses Viroids Prions Today’s Story – Selections from Physics and Chemistry Parts of Stories from Physics and Chemistry that apply to living Cells Chapter parts 2.1, 2.2, 2.3 – should be a review Apply to all infectious agents and environments We will emphasize those that apply to the special circumstances of life If there are parts you do not understand – see me to catch up. Will also lay the foundations for specialized molecules of life Start this topic today Finish topic of Legos and tinker toys next class. 25 6 1/20/25 Class 03 Agenda Reading provided overview (just had it) on atoms, elements, electrons, and bonding In class we are going to build from there Expand on types of bonding and why Expand on chemical reactions of life →centrality of WATER. (solution chemistry) Add concepts of equilibrium and catalysis Order of presentation will be different from the book, but story is same As time permits, we will move to the special role of assembly of legos and tinkertoys… Carbohydrates Lipids and sterols Atoms and Elements... “When I was a lad”, we only cared about four elements: Earth Air Fire Water (that is a joke – don’t write it down!) 37 8 1/20/25 By the time I was in college -- Chemists and Physicists had identified 103 elements (more added since then – but none that occur naturally) They have leaned a lot about the physical laws that create those elements and their individual properties Protons, neutrons in the nucleus, electrons in shells. All important – but not for what we are talking about in this course Microorganisms [MOs] learned about elements and their properties by trial and error – and learned to use them. We will focus on what those key characteristics are and how MOs use them I will leave it to other classes to explain where those traits come from. The molecules of life, the “compounds”, center around six elements (CHONPS) Carbon, Hydrogen, Oxygen Nitrogen, Phosphorus, Sulfur (There are many more elements that play important roles as electrolytes, metals, and more. They will show up on later talks.) But these six easily form COVALENT bonds (where electrons are shared) to form new, more complex compounds essential for life chemistry. And among those elements, CARBON is King 4 Carbon Most stable when it has four covalent bonds Allows it to bind to itself in chains of any length while still having other bonds to add variety of structure and activity. The definition of “Organic Chemistry” And the other five elements? At least remember… Hydrogen – 1 covalent bond Oxygen & Sulfur – 2 Nitrogen – 3 Phosphorus – 5 9 Table 2.5 Biologically Important Functional Groups Functional Group Structure Where Found Aldehyde Carbohydrates Amino Amino acids, the subunits of protein Carboxyl Organic acids, including amino acids and fatty acids Hydroxyl Carbohydrates, fatty acids, alcohol, some amino acids Keto Carbohydrates, polypeptides Methyl Some amino acids, attached to DNA Phosphate Nucleotides (subunit of nucleic acids), ATP, signaling molecules Sulfhydryl Part of the amino acid cysteine 10 1/20/25 10 511 12 1/20/25 Water is Key! Life as we know it can only occur in the presence of water.  MOs might be able to survive in stasis w/o water, but none can grow. The essential chemistry of life is mostly solution chemistry And even the “exceptions” require structures that can only exist in water. Highlights a key feature of covalent bonds – They can largely retain their connection between atoms when put into a water environment! Chemical Reactions Compounds are most stable when all possible bonds between atoms are in place In the right circumstances, those bonds can shift, making new compounds Chemical reactions transfer electrons, often involving rearrangement of bonds to form new stable structures When considered as running in only one direction, Reactants are starting components of a reaction that are changed to products Synthesis reaction A + B → AB Decomposition reaction AB → A + B Exchange reactions AB + CD → AD + CB or AB + C → AC + B 613 14 1/20/25 Which Way will Reactions run? Enter the Second Law of Thermodynamics! Essential part of the Story of Physics The universe requires reactions (and everything else) to lose heat and increase disorder (entropy). Requires reactions to run to the lower energy level products BUT LIFE CHEMISTRY REQUIRES THE OPPOSITE Reactions must create higher energy products required for life Also requires the assembly of highly organized structures We will focus on how life manages to push back against the universe – in the short run… Eventual end of the universe is still a low energy fog! In Life Chemistry, reactions (in water) often (always?) run in both directions! Equilibrium of two reactions: AB + CD AD + CB Balance of reactions favors the most stable (lower energy) compounds. Extreme example: CH4 + 2O2 CO2 + 2H2O Symbolically map as “energy levels” CH4 + O2 CO2 + H2O 71/20/25 Sidebar – Reaction Diagram Flat lines at start and end indicate energy levels of reactants and products, respectively. Difference between those level is the difference (or delta) of energy of the reaction. “Hump” at the start represents Activation Energy required, indicating the requirement of addition of energy to start the reaction. CH4 + O2 CO2 + H2O 15 Sidebar – balancing chemical equations May have noticed I threw some extra numbers into the chemical reaction. Needed to balance the number of each kind of atoms on each side. In much of Life Chemistry, you also need to pay attention to the number of reduced or oxidized (redox) electrons – balancing “redox” elements. Not going to go into detail on how – but know that it will come up again in metabolism. → Key Impact: if you do not have sufficient numbers atoms or reduced or oxidized electrons on either side, the reaction cannot run! Important, later. 16 817 18 1/20/25 In Water, things go both directions more readily. Water itself – Oxygen covalently bonded to two Hydrogens But they can, at a low lever, separate in OH- and H+ ions. H – O – H OH- + H+ Equilibrium is the balance of products and reactants when the net rate of the reaction in each direction is the same. In pure water, the H+ concentration is 10-7 molar (= pH 7) In Acidified water (add acid), the concentration is higher, resulting in a lower pH. So, at pH 4, concentration of H+ is 10-4. Still not much, but results in a 1000x increase in availability of H+ Back to Covalent Bonds for a moment We’ve found that some compounds are more stable than others (different energy levels) Also need to realize that in some covalent bonds, the sharing of electrons is not as equal as it could be. Nearly equal: C—C, C—H, and H—H Not so equal: O and N not as nice – hog the electrons Results in a dipole – (slight negative charge) O—H (slight positive charge) We know that + charges are attracted to – charges Same true for dipoles -- slight (+) weakly attracted to slight (–) ➔ Hydrogen Bond 919 20 Hydrogen Bonds Very weak – roughly 1/100 the strength of a Covalent Bond Put a few thousand of them together, and things will stick… Locally, bonds form and unform continuously But across the structure, holds overall →Useful if you want structure that can open up at times, then re-zip! Put a pin here – we will come back in a future class. Meanwhile – we suddenly realize that water is a dipole, hydrogen bonding to other water molecules ➔ And things get interesting! Covalent Bonds—Figure 2.6 Polar covalent bonds result in slight separation of charge Important in biological systems May result in formation of hydrogen bonds Access the text alternative for slide im ages. 1/20/25 20 1021 22 Water, pH, and Buffers—Figure 2.9 Water (H2O) is a polar molecule Hydrogen bonding explains some properties Liquid: hydrogen bonds continually form and break, allowing molecules to slide over one another Solid: each water molecule forms four hydrogen bonds with surrounding water molecules producing a less dense structure called ice ICE is LESS DENSE than LIQUID WATER Also capillary action! Access the text alternative for slide im ages. Water—Figure 2.10 Polar nature makes water an excellent solvent in which solutes are dissolved Polar and charged substances are hydrophilic (“water loving”); dissolve in water Non-polar substances are hydrophobic (“water fearing”); do not dissolve in water Water with dissolved substances freezes at lower temperatures Access the text alternative for slide im ages. 1/20/25 21 22 1123 24 1/20/25 Look back at our covalent bonds in Life Chemistry C—C, C—H combinations – equal sharing – no dipole HYDROPHOBIC Do not dissolve in water In fact, will try to HIDE from water, if possible Involve O or N – now have dipoles HYDROPHILIC Dissolve in water What happens if you have both features in one molecule? Glad you asked – but will answer later… At this point – I admit I’ve been ignoring some things in the reading. Actually, several somethings, but some I do plan to skip. For which of the following topics would you like me to elaborate on the book explanation? Possible uses of different Isotopes in research? A B Something about Buffers? C Did we cover all types of chemical bonds? D Molarity of compounds? 121/20/25 Ions and Ionic Bonds Why did I skip? As far as life is concerned, solid salts are relatively boring. But now that we have added water, it gets interesting! Some elements don’t share electrons at all. They either steal them or give them away Net result is a solid positive or negative charge on each atom. Salt crystals are a lattice of positive and negative charges, balanced overall, but with no identifiable “molecule”. But dissolve in water -- 25 Dissolve in water, and … Ions can take on individual lives of their own as “Electrolytes”. Individual “point” positive or negative charges can be diffused by hydrogen bonding capability of water. If you get fancy with membranes or attractive surfaces, can swap out negative ions for OH- and positive ions for H+, all courtesy of water. And dissolution of salts in water can alter the properties of water Change the freezing or boiling points of water. Change the pH of water to acidic or basic. Change the effective concentration of water. Transport electricity And life will use each of these characteristics to its advantage. 26 1327 28 1/20/25 A couple closing thoughts on Chemical Reactions: Challenge #1 Discussed earlier about how reactions run in both directions -- but favor the direction of the most stable (least energy) compounds. Second Law of Thermodynamics – Entropy increases. But life generally wants to go the other direction – higher energy compounds and lower entropy structures. How does life break the law? Life doesn’t break the law, just hires a good lawyer… Seems you can do pretty much anything you want, as long as you pay for it somehow! General solution – Artificially link together two reactions One, that you really want, that is energetically not favored. And one that you don’t care about much, except that it is energetically favored When run together, net reaction is favorable, and law is satisfied. Example of a can of paint needed on the roof. 1429 30 1/20/25 Chemical Reactions, Challenge #2: How to control reaction Think about a Snickers Bar Family size is about 500,000 calories. Enough energy to boil the blood in my hand and fingers Or if released all at once, probably blow my hand right off Yet, if I were to offer to give it away, any takers? Experience has taught us, safer than it sounds. Key is the Activation Energy Hump! Higher energy reactants stable until energy added to get them over the barrier! 1531 32 1/20/25 If you can reduce the activation energy to a level sufficiently low… Energy at room temperature can be enough to let it find equilibrium. Life is a master of creating specific catalysts – protein enzymes. Catalyst/Enzyme Enzymes (usually protein) Most biologically important chemical reactions occur too slowly at livable temperatures to be useful to a cell Enzymes are biological catalysts that speed the rate of reactions Bind to one or more reactant molecules Stabilize the transition state of the reaction, lowering the required activation energy. CAN ALSO LINK UNRELATED CHEMICAL REACTIONS TO DRIVE UNFAVORABLE REACTIONS. Will come back to in a later class. 1633 34 1/20/25 Summarize to date Physics Story: Second Law of Thermodynamics Chemistry Story: Characteristics of elements Types of bonding (and other interactions) Reactions, including balancing atoms and electrons… Life Chemistry interpretation CHOPS, with Carbon king Water (solution chemistry) driving equilibrium, dominant role of covalent bonds. Equilibrium and Activation energy, combined with specialized catalysts, let us push back against the second law, but only in the short run. → Any Questions on this part? Building more complicated Molecules and Structures Life’s Storyline is to use (and reuse) a set of building blocks that are chained together to make complex structures → think Legos or Tinker Toys Focus on four classes of compounds Carbohydrates Lipids/Sterols Proteins Nucleic Acids 1735 36 Major Classes of Organic Molecules—Table 2.4 TABLE 2.4 Major Classes of Organic Molecules Name Subunits Major Functions Carbohydrates Monosaccharides Structural components of cell walls; energy sources Lipids Varies—subunits are not always similar Some types are important components of cell membranes; energy storage Proteins Amino acids Enzyme catalysts; structural portion of many cell components Nucleic acids Nucleotides DNA Deoxyribonucleotides Genetic information of a cell RNA Ribonucleotides Various roles in protein synthesis; catalysis Carbohydrates—Figure 2.13 Diverse group includes sugars and starches Energy source Energy storage Carbon source Component of DNA and RNA Structural components of cells Carbon, hydrogen, oxygen in 1:2:1 ratio Building block: CH2O “looks like” carbon and water - - Carbohydrate Access the text alternative for slide im ages. 1/20/25 35 36 1837 38 1/20/25 Monosaccharides—Figure 2.14 Monosaccharide: basic unit of carbohydrates 5-carbon sugars include ribose, deoxyribose 6-carbon sugars include glucose, galactose, mannose, fructose Structural isomers: same atoms, but different arrangement Distinct sugars with different properties Access the text alternative for slide im ages. 37 Disaccharides—Figure 2.15 Disaccharides composed of two monosaccharides  Common disaccharides Sucrose (glucose + fructose) Lactose (glucose + galactose) Maltose (glucose + glucose) Dehydration synthesis forms covalent bond between hydroxyl groups of monosaccharides Hydrolysis breaks bond and yields two monosaccharides Access the text alternative for slide im ages. Special case of water addition or removal 38 1939 40 Polysaccharides—Figure 2.16 Polysaccharides are chains of monosaccharides Used for Energy storage, structural components. Not just linear connections – can have branching, linkages, with different characteristics Important polymers of glucose: Cellulose Starch Glycogen Dextran Chitin, agar also important Access the text alternative for slide im ages. Lipids: Energy Storage, Structures, and Insulation Lipids are non-polar, hydrophobic molecules Diverse group defined by slight solubility in water Hydrophobic (water-hating) characteristics result in clustering of lipids in water. We will focus on fatty acid derivatives and sterols 1/20/25 39 40 2041 42 Fatty Acids—Figure 2.17 Fatty acids are linear carbon skeletons with a carboxyl group (—COOH) at one end Saturated fatty acids No double bonds Tails pack tightly so solid at room temperature Unsaturated fatty acids Double bonds between carbon atoms Kinks prevent tight packing so liquid at room temperature (oils) Access the text alternative for slide im ages. Simple Lipids Most natural fatty acids are cis: hydrogens attached to same side of double bond Trans: hydrogens on opposite sides of double bond (linked to certain health problems) Access the text alternative for slide im ages. 1/20/25 41 42 21Triglycerides—Figure 2.18 Triglycerides: most common simple lipids Fats or oils composed of three fatty acids linked to glycerol Fatty acids: linear chains of bonded C, H atoms with carboxyl group at one end Access the text alternative for slide im ages. 43 Triglycerides are very hydrophobic.  Suspended in water, form either bubbles of oil or lumps of fat. Think Italian salad dressing – or soups/stews rich in ”fats” But what would happen if you combined hydrophobic and hydrophilic parts in the same molecule? 44 1/20/25 43 221/20/25 In water, a molecule with both (hydrophobic) and hydrophilic components would most likely -- (A). Break apart, because hydrophobic and hydrophilic parts cannot get along with each other. A B (B). Float on top of the water, with the hydrophobic parts sticking into air C (C). Form small bubbles (vesicles) with the hydrophilic parts in contact with the water and the hydrophobic parts forming a oil droplet inside the bubble. (D). Form a layered structure (membrane) with hydrophilic parts in contact with the water on top and bottom and with hydrophobic pars in between. D 45 Phospholipids—Figure 2.19 Compound lipids contain fatty acids and glycerol in addition to a non-lipid component Phospholipids contain hydrophilic phosphate group and hydrophobic fatty acid tails If oil floating on top of water – cluster at the interface, polar head in water, fatty acids in oil! Access the text alternative for slide im ages. 46 46 231/20/25 But carries its own “oil” Form lipid bilayer with phosphate groups oriented outward toward aqueous environments Essential component of cytoplasmic membranes Lipoproteins, lipopolysaccharides also compound lipids 47 Membranes (Lipid Bilayers) are one of the most important inventions of Life! Dependence on concentration of reactants The speed of a chemical reaction is dependent on the concentration of reactants Higher concentration means faster reaction But of Life’s reactants and products diffuse in water Diluted reactants make for slow reactions Also makes it easy for other life forms to steal Need a container that limits diffusion, but sufficiently flexible to take on any shape and able to grow with the organism!  We will eventually need to allow for controlled passage of compounds. But that will come in a different class! 48 24Steroids—Figure 2.20 – another mixed hydrophobic/hydrophilic molecule Steroids have characteristic four-ring structure – rigid!!! Classified as lipids because they are poorly soluble in water Sterols such as cholesterol have hydroxyl group attached to one of the rings Often part of eukaryotic plasma membrane Role in Fungal disease treatment… Other steroids include hormones Cortisol, progesterone, testosterone Access the text alternative for slide im ages. 49 Class 04 Legos and Tinker Toys Part 2 Jan 30, 2025 Reading Ch 2.4b Announcements Last day for Class 01 HW!!! – office hours from right after class to 2 pm. In-Class – two traits of water. Expected physical traits of Water. Saw lots of confusion instead! Yes, life depends on water. Yes, covalent bonds are important because they survive in water (as opposed to ionic bonds), but NO, water doesn’t make covalent bonds! Many physical traits that make water important for life – most related to its being a dipole hydrogen bonding, universal solvent, capillary action, specific heat, equilibrium between OH- and H+, dissolution of ions, solid form floats in liquid and more… 13 4 1/30/25 Review: Physics – Second Law Chemistry – protons/redox, bonds, redox Chemistry through the lens of life Water, solutions, ions, hydrophobic, hydrophilic Reactions and balance!, equilibrium Major types of compounds Carbohydrates Energy source (mono and disaccharides Energy storage (polymers) Structural components (polymers) Information components (polymers) Identification (hybrid) Lipids Energy source, energy storage Lipid bilayer membrane – concentrating chemicals Hormones (sterols) Today – two big covalent components, both polymers Proteins Structure Enzymes Signals/recognition Nucleic Acids (DNA and RNA) Information storage and transfer Also, some enzymes (“ribozymes”) and structure (ribosomes) →Today’s focus – structure and properties of these polymers 25 6 1/30/25 Proteins (or poly-peptides) Multiple layers of structure Basic structural component – a polymer of “Amino Acids” AMINO ACID STRUCTURE Over Arching Story for Proteins a LINEAR chain of a small set of amino acids can provide an unlimited repertoire of specific structures and functions!! 37 8 1/30/25 Amino acids combine to form Peptide Bond Covalent bond between the amino acid amine with the carboxy group of the growing peptide chain. Peptide bond has a preferred structure, more constrained than a C—C covalent bond. PRIMARY STRUCTURE: the length and exact sequence and direction of amino acids of the peptide chain Primary structure uses covalent bonds, can survive a broad range of temperature and chemical conditions. The peptide backbone can fold into one of several preferred sub-structures stabilized by Hydrogen Bonds → Secondary Structure! Alpha Helix Beta Pleated Sheet Other structures as well. In each case, the oxygen and nitrogen groups are in line and can form Hydrogen Bonds, Stabilizing the structure. Not absolute – flexible structure, affected by temperature and chemical conditions. Also affected by “R” groups. 49 10 1/30/25 Amino Acids – second look When R = H, both positions equivalent. If add a different group chemically – would be equal % on one side or other. If add a different group enzymatically, all added ONLY to one side. Produces an Optical Isomer! Technically could be ‘D’ or ’L’ – But all proteins in any life form (or acellular agents) ONLY USE ‘L’-amino acids in their proteins Why do we care? Why Do We Care about only ‘L-’? Evidence that all life is related (universal tree of life) – all proteins L Means that all proteins can serve as food for life (break down into subunits and reassemble) Only the “correct” optical isomer may work in certain enzyme reactions For our bodies, also means if a ’D’ amino acid is seen, something is wrong! Bacteria do use D-Amino Acids in special structure (NOT Protein!) If a neutrophil or macrophage find a D-aa lying around, they go crazy and start searching for bacteria! 511 12 1/30/25 R groups make the protein! Peptide backbone is relatively uninteresting Can form hydrogen bonds (HBs) with water (so, soluble) Can form HB with self in defined structures (e.g., alpha helix, beta sheet). Very limited repertoire R-groups are defining! Life has limited the pool to 20 universal amino acids. Can classify them in different ways Know the ways, some examples…. One of the twenty Amino Acids (Glycine) has no R group (so, neither ‘D’ nor ‘L’) Good fit for tight spaces Okay with hydrophobic Okay with hydrophilic No charge 613 14 1/30/25 Five R groups have alkane chains Hate water (hydrophobic), so try to tuck inside the protein structure! Think Leucine… One of these has the added characteristic that it cannot be part of an alpha helix or beta chain – disrupting sub- structures. Four more are also hydrophobic, but with special characteristics Aromatic Rings Phenylalanine and Tryptophan – (also Tyrosine, coming up) Sulfur containing! Cysteine – catalytic activity, also disulfide bonding Methionine – methylation, also protection from oxidation Also protein starting amino acid… more later 715 16 1/30/25 Five are hydrophilic (love water), but uncharged. Three of these (Serine, Theonine, & Tyrosine) can have phosphate attached or removed, changing the structure and activity of an existing protein. (Kinases and Phosphatases.) Five are charged (and hydrophilic) at neutral pH. Three can have a positive charge. Histidine readily changers between positive and neutral at “normal pH” Lysine and Arginine always positive in normal pH range. Lysine can also form a second peptide bond through its amino group! Two (Aspartic acid & glutamic acid) have a negative charge in normal pH range, And both can from second peptide bonds through their acid groups. 81/30/25 Second look at Primary Structure Bacteria have thousands of different proteins. Each protein has a defined sequence of Amino Acids that results in a specific “fold” for that chain Every copy is exactly duplicated! What happens if that sequence changes/mutates? 17 A A 200 amino acid peptide folds to an active enzyme. Which of following is true? (A). Changing only one amino acid (to a different amino acid) won’t affect the function, as long as the amino acid is not part of the active site of the enzyme. (B). Changing 50 amino acids (to 50 other amino acids) is certain to affect the function of the enzyme. C (C). Exchanging an amino acid for an amino acid with similar characteristics is not likely to affect the function of the enzyme. (D). Cutting off the last 10 amino acids on the Carboxy terminal end of the chain is not likely to affect the function of the enzyme. D B 18 919 20 1/30/25 The Story focuses on characteristics of Amino Acid But you need some specifics. For this class, know the categories and an example of each category Isoleucine/Leucine – Large Hydrophobic Alanine – Small Hydrophobic Glycine – smallest amino acid (R chain is “H”) Serine – hydrophilic, uncharged, phosphorylation site Lysine – positively charged Glutamate (or Glutamic Acid – negatively charged Methionine – another large hydrophobic – but special…. Proline – disrupter of secondary structure Which amino acid exchange is least likely to affect the function of an enzyme? (A). Exchanging Leucine with Isoleucine. A B (B). Exchanging Arginine with aspartate. C (C). Exchanging Glycine with Tryptophan. D (D). Exchanging Histidine with Proline. 101/30/25 A B With Phospholipids, mix of hydrophilic and hydrophobic generated a membrane bilayer. What happens when you mix different AAs into a single molecule? Amino acids with hydrophilic residues will extend into the water and membrane lipids will cover hydrophobic residues. Amino acids with hydrophilic amino acids will extend into water with random clumps of hydrophobic amino acids stuck together. C Will fold to one dominant structure, with mostly hydrophilic residues on the outside and mostly hydrophobic residues in the inside. Two or more stable structures can form from the same amino acid chain, though with mostly hydrophilic residues on the outside and mostly hydrophobic residues in the inside. D 21 Protein sequence evolved to consistently fold into one dominant structure Folding driven by combination of Hydrogen bonding into common secondary structures Hydrophobic residues hiding from water Hydrophilic residues seeking water Secondary ionic and bonding effects (after folding) Can be further modified by addition of other compounds to the folded chain Sugars Lipids Charged compounds (e.g., Phosphate) other 22 11Protein Denaturation—Figure 2.26 Extreme “wrong” conditions can cause misfolding! Can be caused by high temperature (cooking!), extreme pH, certain solvents Protein may become non- functional Function may be restored by refolding proteins (Chaperonins). Or non-functional protein may be digested to provide amino acids for synthesis of new proteins. Access the text alternative for slide im ages. 23 Proteins synthesized from the Amino end Adding the next correct Amino acid to the carboxy terminus of the growing chain → PRIMARY STRUCTURE Folds as it is synthesized – first SECONDARY STRUCTURE Then TERTIARY STRUCTURE: Specific overall fold – very specific to that protein’s function – dictated by the sequence of amino acids Should be just one – except see prions! QUATERNARY STRUCTURE: Entire Proteins may also cluster into multimeric proteins to improve effectiveness. 24 1/30/25 23 1225 26 1/30/25 Proteins do it all! Enzyme catalysis Transport Signal reception Regulation Motility Support (Except information storage?) Generally, requires specific pH and temperature range (aligning with the normal environment of the organism!). If time – Enzyme Demonstration A I am willing to participate in a short demonstration in front of the class. B No way you are getting me up front and subject to possible ridicule! 1327 28 1/30/25 Enzymes Shape (structure) is Key!!! Each protein designed to do a single reaction step! The peptide chain is folded to form a small, flexible “pocket” or binding site that holds the binding site to react one or a few specific R groups to catalyze the reaction. Makes it easier to bind bring reactants and products together Reduces the activation energy required by stabilizing transition state. So, hundreds of amino acids create the folded protein where a few amino acid R groups are perfectly positioned to facilitate the reaction! Different polymer, different story…. 1429 30 1/30/25 Overarching Story for Nucleic Acids – Information! Story of DNA – a linear (and directional) polymer responsible for the accurate and permanent storage of all information needed for Life, with safeguards to ensure Story of RNA – a linear and directional polymer responsible for the controllable and temporary transmission and implementation of information to enable the process of life. Last major set of Tinker Toys: Nucleic Acids  Two main forms of nucleic acids, polymers of: Ribose Nucleic Acid (RNA) Or Deoxyribose Nucleic Acid (DNA) Main sugar differs in the presence or absence of a single Oxygen atom. Primary functions of DNA are information storage, replication, and transmission. Primary functions of RNA include Transfer and translation of Information Structures Catalytic functions 1531 32 DNA Subunit DNA Subunit 1/30/25 2-carbon -OH for Ribose and RNA!!!! 1633 34 1/30/25 Bases for DNA (and RNA) Nucleobases include Purines: adenine (A), guanine (G) Two fused rings Pyrimidines: cytosine (C), thymine (T), uracil (U) Single ring structure Uracil (U) found only in RNA Backbone chain Backbone of alternating sugar and phosphate molecules Covalent bond between phosphate group of one nucleotide and sugar of the next Phosphate group is on the 5ʹ end of the strand Hydroxyl group of sugar is on the 3ʹ end of the strand Chain is synthesized by adding to the 3’-OH end. 1735 36 1/30/25 But DNA is usually found as double strand! Two strands run in opposite directions! 5’ ------> 3’ 3’