Older blogs below

December 2016

Review and Additional Study hints

  • Early Stuff

  • Molecules:
  • Functional groups. Don't memorize lots of details. For example, if you read the word "acetate," you should know 'that must be an acid that's lost it's proton." but you would not need to know how to draw it.
    1. Carbonyl in either keto or aldehyde along with Nitrogens: good H-bond acceptor . Just don't be scared if you see one.
    1. OH in an alcohol and NH in amine: Good H bond donor and the O or N can be an acceptor. You should know this.
    1. Organic acid protonated or deprotonated (-ate ending). Know it is a defining part of an "amino acid."
    1. OH in organic acid NOT an alcohol.
    1. Amino, the other defining part of an amino acid.
    1. Unsaturated C=Bonds in either cis or trans and the importances of cis in biology. Know how these effect fatty acids.
    1. Phospho groups especially importance in ATP and chemistry of DNA and RNA
  • Bigger substituents:
    1. Purine (Big) and pyrimidine (small) bases in DNA. GC has three bonds and is more heat-stable. A-T has 2 and is less heat stable.
    1. Ribose and deoxyribose in the ring form (be able to spot 5' and 3' in DNA or RNA).
    1. Fatty acids (a good place to think about saturate and unsaturated bonds in cis and trans).
    1. The importance of stereoisomers in biology: that the mirror form of molecules may not work or bind the same way. You won't need to recognize these distinctions. But, if I ask about D or L forms being different in Biology.
  • Polymers: Made by dehydration reaction (dehydration synthesis…take out H2O) and taken apart by hydrolysis (add water).
    1. Structure of starch, cellulose and glycogen and what they do in which type of organism (plant or animal). Particularly, remind yourself of the differences in hydrogen bond patterns in cellulose and starch, and how that derives from the beta versus alpha 1-4 link
    1. Amino acid structure. Identify amino, carboxyl and alpha carbon as well as the "R" group. You don't have to memorize the amino acids.
    1. Lipids. Recognized sterols versus fatty-acid lipids. Recognize fat versus phospholipid. Know basic roles. (Phospholipids in the membrane, Cholesterol regulating membrane fluidity and used as basis for hormones).
  • Macromolecules:
    1. In proteins, know primary, secondary, tertiary and quaternary structure and how they relate to each other.
    1. Know alpha helix and beta strand (recognize in structure...ribbon representation, for example) and that hydrogen bonds involving carbonyl and amino groups in the "Backbone" lead to these secondary structures. The main point here is denaturing at higher temperature disrupts H-bonds, unfolds tertiary and eventually secondary structure, but does not break (hydrolyze) the peptide bonds of the backbone.
    1. Know the types of interactions that lead to tertiary structure (more H-bonds, hydrophobic interactions; salt bridges (ionic interactions) and covalent S-S bonds when Cysteine is involved).
    1. In carbohydrates...covered above
    1. In lipids...bilayer formation and the basic structure of the bilayer
    1. Nucleic acid: recognized 5' and 3' ends. Describe chemical polarity and the notion of "antiparallel."
  • Enzymes:
    1. Review my blog on the various steps. Minimally, we have to consider an on-rate, catalytic rate and an off rate, all of which can be modified by mutation, changed by interaction with another protein, and selected and fine-tuned by evolution (or a bio engineer), so that each enzyme would differ in the details. To be clear, I don't need you to know details, just THAT these things happen because of changes to the fine shape of the protein. It's important in the context of questions involving drugs or mutations and how they affect things as well as how proteins regulate each other. Again…this is not a lot of memorization. The whole idea that modifications to a protein or interactions with other molecules, including proteins, will alter function. This is how drugs work and how biology is regulated.
    1. Saturation kinetics and what the graph means. Remember that the graph flattens out when the initial concentration of substrate saturates the enzyme. Adding more doesn't increase the rate because all the enzyme is occupied. It's already going at its maximum rate.
    1. Know how to show Km and Vmax and what the effect of competitive and non-competitive inhibitors are. In particular, how the binding of product leads to the most basic kind of feedback inhibition. This seems like a lot for what will likely be worth a point or two. Don't study the hell out of this. Basically, just recognize how the graphs of activity are affected and have an idea of why.
    1. "Affector molecules," often other proteins, can alter any of an enzyme's attributes: binding to substratee; catalytic rate; off rate of product....any of it. (This will be critical as we look at regulation of cell cycle etc…discussed in "7a"). This idea is mentioned above as well.
  • Cells. Brief, one or two sentence description/definition of:
    1. Plasma membrane
    1. Nucleus
    1. Nucleolus
    1. Mitochondria
    1. Centrosome
    1. Endoplasmic reticulum
    1. Golgi
    1. Transport vesicles
    1. Exo/endocytosis
    1. Actin/microfilaments
    1. Tubulin/microtubules
    1. Intermediate filaments
    1. Chloroplast (plant)
    1. Cell wall (plant)
    1. Smooth ER
Know the key differences between prokaryote and eukaryote and between plant and animal cells.
  • When you think about these structures and what they do, focus on what would happen if a chemical or disease or mutation screwed them up. Remember all the questions I ask about things like "This drug allows ions to pass through lipid bilayers" or this mutation causes vesicle transport to be blocked. Think about "what will happen if…" or "what could be the cause of…" types of questions.
    Also, assume there will be a question about osmosis and hypertonic/hypotonic solutions. Remember that plant cells like to be in hypotonic solution because that swells them up to fill the cell wall well. Animal cells like to be in "isotonic" (same salt concentration).
  • Cellular structure, greater detail:
    1. Membrane trafficking and protein transport (how does a protein synthesized in the ER get secreted or put in the membrane?
    1. Role of the three components of the cytoskeleton. The proteins main proteins that make them up and how each does different, sometimes overlapping things in the cell.
    1. Cell-surface and cell-cell interface: Gap junctions; tight junctions; desmosomes focal adhesions. Interaction with the extracellular matrix. For this, the question may be very general and you can answer choosing the cell type you studied.
  • Respiration and Photosynthesis: The main big question that will likely cover this will be on the second, group effort day.
  • Respiration: Three components of the process and where the small and big payoff of ATP happen. Know the molecule from each step that is important for the next.
    1. Glycolysis: know the rate-limiting early step (phosphofructokinase) and why that might be important. Know the general points:
      1. 2ATP in, 4 out for a net 2 gain
      1. There are also 2NADH created, which is also a good energy source and, if O2 is around, can lead to more ATP.
      1. If no oxygen, the NADH must be oxidized to NAD+ by some sort of fermentation.
      1. Pyruvate transported to the mitochondria for the next steps
    1. Citric Acid cycle: Main products are some ATP and GTP through substrate-level phosphorylation and NADH. CO2 released mostly in this cycle.
    1. NADH feeds into electron transport which leads to the pumping of protons across membrane. The protons feed the next step. Final recipient of the electrons is Oxygen, resulting in water as a product.
    1. Protons drive the ATP synthase.
    1. Structure of the mitochondria (inner/outer membrane and intermembrane space...what happens where and where the main components are). As always, I like to ask structure-function questions. I love to compare photosynthesis to respiration (the water-oxygen-electron connection is a favorite). But, I've recently given you one of those. I will keep it basic on this test.
  • Photosynthesis
    1. General structure of a leaf: stoma; cuticle; chloroplast; thylakoid; grana; That's enough silly names.
    1. Light harvesting complex...other pigments that feed energy to:
    1. The reaction center, specialized chlorophyl.
    1. Basic Z scheme: Photons excite electron in PSII, which are sent down an electron transport chain off to PSI. Splitting water (Oxygen production) replaces the electrons in PS II (Apparently, this portion of PSII is the only biological case where water is Electrons travel down and H+ is pumped into the Thylakoid lumen. The electron is passed to PSI, where it is hit with another photon and excited to a higher level than the first photon hit. The big win here is the passing of the electrons to the higher-energy NADPH2.
    1. Protons drive ATP synthase and NADPH2 feeds into the calvin cycle, where, almost the reverse of Citric Acid cycle, NADPH2 is oxidized to NADP and CO2 is reduced by addition to growing carbon chain.
    1. Circular flow...just in PSI. Gets some protons pumped, but no NADPH2.
  • The number one thing you should know about me and how I view this course is that I want you ALL to succeed. I want to write a test that gives each of you the chance to shine, and challenges each of you to do more than you think you can. We'll see if I'm good enough to do that.
  • Study Guide for recent stuff and other guidelines.

  • You can review the previous test. Assume that the level of detail, particularly for the first test, will be lower, but that you will be expected to put things together.
  • For Meiosis and Mitosis:

  • Be able to recognize/name the basic phases.
  • Know the role and names for the: chromosome; homologous chromosomes; sister chromatid; centrioles (spindle-pole bodies); Kinetochore; Centromere; kinetochore and non-kinetochore microtubules; motor proteins (dynein).
  • Know the key differences between mitosis (replicate once, divide once, generate two cells with identical DNA to the parent) and meiosis (replicate once, divide twice, separation of homologous chromosomes at anaphase I, separation of sister chromatids at meiosis II, generate four cells with exactly ½ the DNA of parent—one copy of each gene). Be able to follow that out on a diagram.
  • For DNA Replication:

  • Know the basics of chromosome condensation (just really that Histones and other proteins allow DNA to pack really well in a small space)
  • Know names and roles of: DNA Polymerase III, DNA Polymerase I; Primes; Ligase; Okazaki fragment.
  • Given a sequence of DNA with polarity, make sure you can write the complementary sequence in DNA or RNA (U instead of T) in the right polarity.
  • Differences between "Leading" and "Lagging" strand synthesis.
  • For Cell Cycle:

  • Know: names and roles of MPF; Cyclin; and Cyclin-dependent Kinase (CDK).
  • Know the purpose of a "check point" and at least where the main ones are. Be able to correlate the time of expression of a cyclin with a particular checkpoint.
  • Know the phases G1; G0; S; G2 and M.
  • Important connections:

  • I will update more of these by later. Check back.
  • DNA content due to DNA Replication is an indicator of phase of the cycle and whether mitosis or meiosis is in play (as in the diagram we have used of DNA content versus time).
  • Mutations or inhibitors that block a particular checkpoint (at the level of the cyclin or CDK, for example) cause cells to arrest (stop) the cell cycle at that point

The Operon


An operon is a system that exists in bacteria, but not in eukaryotes, for regulating several genes together. Suppose, for example, you are a bacteria that sometimes encounters the sugar lactose. It would be good to have the genes for proteins to process that. You’d need a transport protein to get the lactose into the cell efficiently, and an enzyme to break the lactose into its components, Glucose (you know how that can be used) and Galactose (which you can also convert to glucose).
But, you wouldn’t want to be making these proteins all the time. It would be a waste of energy. Ideally, you would have a system that kept the genes for these proteins “Off,” but then be able to sense the presence of lactose and turn the genes “On.”
That is the
lac operon. And it serves as an example.

What an operon needs

  1. A stretch of DNA that encodes several proteins on ONE mRNA. The ribosome will make all of them reading the same message. This does not happen in Eukaryotes.
  2. Promoter: a site on the DNA recognized by RNA polymerase (which carries it’s own transcription factor to bind the promoter sequence, in E. coli).
  3. Operator: A sequence in the DNA that binds another protein, called Repressor. When repressor is bound, the polymerase cannot get access to the promoter.
  4. A Repressor: The protein that binds the Operator and prevents transcription. It is usually encoded nearby, transcribed from another promoter. Importantly, the repressor has to exist in two states: One that binds the operator and prevents transcription of the genes and one that does not.
  5. Effector molecule: molecule, such as lactose in the example of the lac operon, that binds to repressor and switches it between the two states.

Below is a general picture taken from Wikipedia.
The players are numbered below as:
  1. RNA Polymerase
  2. Repressor
  3. Promoter
  4. Operator
  5. Inducer (such as Lactose)
  6. 6, 7 and 8: the coding sequences for several proteins.
In the first panel, the repressor is bound because the inducer is absent. RNA polymerase cannot gain access to the gene.
In the second panel, the inducer changes the shape of the repressor, which causes it to release from the operator. Transcription can then occur.
Note, that there are also cases where the repressor binds only in the presence of the effector molecule. So, you can turn off an operon when the effector is present. This is great for feedback inhibition. The Trp operon is an example of this and is described in the book.

Telomerase and the Hayflick Limit

Telomeres and Telomerase:

After reading this, please read this short news piece from the journal "Nature."
Two problems:
  1. As we have discussed, the chemistry of replication leaves the lagging strand not fully replicated. There is a 3' extension of what had been the template. This would lead to shortening of the chromosome with each round of replication.
  2. We have not previously discussed this, but the ends of broken chromosomes, or just free ends of linear DNA, lead to recombination or “splicing” together of these fragments. We see the results of this in certain translocations we have discussed. Also, free ends of DNA tend to be degraded by enzymes quickly. So, what is special about the ends of our chromosomes that keeps this from happening?
Telomeres can be described as the specialized ends of chromosomes that protect the rest of chromosome and keep it stable.

Cancer and the Hayflick Limit

Our cells seem to go through a fixed number of divisions before they no longer can keep going. This is called the “Hayflick Limit” after the person who noticed it.
However, cancer cells are immortal…they overcome this limit. Also, there must be a way for cells to fix the problem so that we can “reset” the Hayflick limit when a new embryo is formed. One more thing: one-celled organisms don’t have a Hayflick limit. They can grow indefinitely. All of this pointed to some enzyme activity needed to maintain the ends.

The Sequence:

Well, since we are talking about DNA, it seems likely that there is some specific sequence that corresponds to the Telomere. There is. In humans and other vertebrates, the sequence is the short repeat 5'(TTAGGG)n, where “n” is an integer between 300 and 8000. So, that can be 50,000 bases.
  • How does it get there?
  • How does it achieve the goals above?


The enzyme Telomerase is a little unusual. It has a DNA polymerase activity and needs a 3' end to which it adds. But, it carries a short RNA that acts as its template. So, it finds the free 3' end, which is already longer than the newly replicated strand (due to the lagging-strand problem), uses the internal template to extend the repeated sequence over and over again. Because it uses RNA as a template, but polymerizes DNA, it is known as an RNA-dependent DNA polymerase, also known as “reverse transcriptase,” since it is the opposite of transcription. The image is stolen from Wikipedia and shows the repeating sequence
That’s how it gets there.
It fixes the shortening problem by just adding the sequence. This can then serve as a template for more lagging-strand synthesis. That will still leave a short 3' extension, but will re-lengthen the telomere.
It’s an interesting enzyme.I’ve found many other images with great detail on it, but decided to steal this one:

It shows that there is a long complex RNA that interacts with several proteins (Dyskerin, TERT and some smaller ones). The RNA is much more than the template. It folds into a complex structure that fits into the proteins. The reason I included this one because it makes reference to a couple of forms of a genetic disease known as “Dyskeratosis.” This is a version of premature aging where the effects are seen as premature organ failure, rather than an old-looking outward appearance. Does it make sense that mutations to genes in the telomerase complex would lead to that?

As for how it solves problem number two, the extended 3’ end will fold back around and, along with some accessory proteins, will form a complex, stable structure shown below in cartoon form:

This cartoon is from from:

A more realistic view of the DNA in it’s four-strand form is below: (Image from Wikipedia):


The green dot is a monvalent cation.
This depicts how the structure forms. Note that the strands are
Parallel, not antiparallel.
(image from this website: