Thursday, May 10, 2012

3 Major Themes of Biochem

     The 3 major themes which seemed to connect all of Biochem are: structure, reactivity, and regulation.

Structure
     I've long heard in various science classes that "structure determines function." Yet, never before was this mantra more evident than throughout the various topics of Biochem. "Structure" was important in every topic covered, such as proteins (with 4 types of structure), nucleic acids, carbohydrates, lipids, and allosteric enzymes, to name just a few. The functionality of each of these types of molecules was dictated by their respective structures. Though I knew, for example, that the double-helix structure of DNA was crucial in its replication, Biochem introduced a new level of understanding. This is true for all the structures covered. Structure is the difference between a saturated and an unsaturated fat. Structure determines the action of allosteric enzymes. Structure was everywhere, and gaining a new level of understanding about structures facilitated comprehension of the function and reactivity of each respective molecule.

Reactivity
     The reactivity of molecules was a consistent theme, determined by the previously highlighted theme of "structure." The conformation of an allosteric enzyme, for instance, dictates whether it can catalyze a reaction or not. The reactivity of DNA Polymerase during replication is dependent on a free 3' hydroxyl group. The reactions of protein synthesis depend on the availability of each necessary component. So while it is easy to identify the key players in various reactions, understanding how, why, and when they actually are able to react with one another, was a key theme in Biochem. Some of these determining factors were known beforehand, but again Biochem illustrated these properties in new detail. I used to know DNA replication required an RNA primer, but now I know why. I used to know that enzymes can react under certain conditions and not others, and now I have a better understanding of why this is for many catalysts. The differences in reactivity of various molecules proved to be essential mechanisms of control for the numerous processes essential to life.

Regulation
     Combining the knowledge of various reactivities determined by structure, leads to the important theme of regulation. Sure certain molecules have certain properties which allow for specific reactions, but obviously the body does not want all of these reactions occurring at all times, uncontrolled. Regulation of biological functions is critical in terms of efficiency and necessity. DNA replication, transcription, translation, metabolism, etc. are all regulated processes, and they are regulated at multiple control points. I knew long before this class that most processes in the body were regulated, but this class taught me how, and why. I learned, for example, how one regulatory molecule may turn on a certain process, and how a different molecule may turn that same process off. I also learned how the same molecule can turn on some processes, while turning off others.

     The new found understanding of structure, reactivity, and regulation are all interconnected. These three themes were central to all the material we covered, and they served as yet another way to connect these complicated and diverse topics.

The Connection Between Glucose and Energy

     The body's principle source of energy is ATP, which is synthesized through a series of reactions. In humans, glucose serves as the most basic input for these reactions, which ultimately produces ATP for other bodily functions. 

     Glucose is a sugar monomer; more complex sugars and carbohydrates can be broken down to this basic form to then be utilized in ATP synthesis. The first pathway involved in this process is a series of 10 reactions known as glycolysis. The steps are as follows:
  1. Glucose is phosphorylated (a phosphate group is added from an ATP), to produce glucose-6-phosphate.
  2. Glucose-6-phosphate isomerizes (same composition, but rearranged), to produce fructose-6-phosphate.
  3. Fructose-6-phosphate is phosphorylated (again expending an ATP), to produce fructose-1,6,-bisphosphate.
  4. Fructose-1,6-bisphosphate is cleaved, producing glyceraldehyde-3-phosphate and dihydroxyacetone phosphate.
  5. Dihydroxyacetone phosphate isomerizes to glyceraldehyde-3-phosphate.
  6. Each of the two glyceraldehyde-3-phosphates are oxidized to produce two 1-3,bisphosphateglycerates.
  7. Each of the two 1-3,bisphosphateglycerates transfers a phosphate group to an ADP, producing two ATPs and two 3-phosphoglycerates.
  8. Each of the two 3-phosphoglycerates isomerizes to two 2-phosphoglycerates.
  9. Each of the two 2-phosphoglycerates are dehydrated to produce two phosphoenolpyruvates (PEPs).
  10. Each of the two PEPs transfers a phosphate group to an ADP, producing two ATPs and two pyruvates.

*So for every one molecule of glucose, a cycle of glycolysis produces two pyruvates and two ATPs (4 were produced, but 2 were expended, netting 2 ATP).*

     Alternatively, if glucose is in excess or ATP is not immediately necessary, glucose can be stored in the form of glycogen via glycogen synthesis reactions. Once stored, glycogen can be broken back down into glucose for the aforementioned processing, as needed.

     Glycolysis is just the first step in ATP synthesis. Products of this step will enter the citric acid cycle (an 8-step cycle), which in turn produces the necessary inputs for the electron transport chain and oxidative phosphorylation (under aerobic conditions). Through multiple control points and allosteric enzymatic regulations, this complicated process generates the energy we need to go about our lives. Though the multiple steps are complicated, it is the simple sugar monomer, glucose, which serves as the initial fuel for the steps to follow!

Tuesday, April 3, 2012

More Connections With Past Knowledge

     Connecting past knowledge and concepts to form a cohesive understanding of issues, seems to be a constant theme in Biochemistry. At times, it feels like that is Biochemistry's main function for me: to construct bridges connecting past concepts out of new information and increased details of earlier topics. I go to class wondering what topic from past courses will come up today in a new light which helps me better understand underlying principles.

     The connections are everywhere, and have symbolized the value of this course for me. So for example, as we study replication, DNA, RNA, translation, and transcription, I feel as though I am able to better grasp what we discuss. A "phosphate sugar backbone" used to just be a "thing" to memorize as part of the structure of DNA. Now for me, it is a molecular structure which I could easily draw and explain how and why bonds form and why certain 3D conformations of structures are dictated by chemical properties. I learned about the presence of the backbone in earlier Biology classes. I learned about bonding properties and stereochemistry in Organic Chem. But now, in Biochemistry, the two previously independent ideas have been connected in a way that has enhanced my ability to grasp their individual roles in the big picture.

     The previously mentioned example is just that, only an example. This has been occurring weekly, chapter to chapter, class to class. And at the risk of calling myself out as a "nerd," I love it. It is refreshing and engaging to be able to understand things at such a different level. I think in earlier science classes we have all had times we had to just accept things presented to us. We might have asked "how?" or "why?" certain things were the way they were, but the fair and truthful answer at times, was just to accept it; it might have been outside of the scope of the class to delve into that level of detail, or more simply, it just may have been over our heads.

    I feel like this is exactly where Biochem has come in. It's continually providing answers to my former questions of "why?" or "how?" which used to be over my head. Instead now, the "hows" and "whys" are explanations I understand due to lessons learned in Biology, Chemistry, or Organic Chem. Whether it has been amino acids, DNA replication, Vitamins, or any other concept that has come up, Biochem continues to bridge previously studied ideas to allow me to better grasp the big picture.

Friday, March 2, 2012

Interesting Biochem Website

     An interesting Biochemistry website I found is The Journal of Biological Chemistry (JBC).

     The JBC website is fascinating, and filled with more information than any one person could ever absorb! Unlike other journals I have looked through, this website is very user friendly; you do not have to have a PhD to understand the resources, let alone navigate them.
     Aside from the usual search features, articles, reviews, and archives, there a number of interesting features worth noting. The JBC has links to "Affinity Groups" which lead you to pages tailored for specific disciplines such as enzymology, gene regulation, RNA, or signal transduction.
     The website also offers downloads of podcasts which is extremely helpful. We might not always have enough time to read every article of interest, so it is helpful to be able to download and listen to discussions in the car or wherever and whenever we want. The podcasts I have listened to were interviews with the authors of various papers; it also was helpful to hear authors discuss their work and findings in their own voice and answering questions, rather than just reading a standard article.
     On top of the podcasts, the JBC actually offers an iPhone and iPad app to keep up to date with the journal. Overall, there is a vast array of information and resources available on the JBC website which help connect Biochem to medicine, research, and so much more. Making these connections helps me better understand the topics we study by keeping up to date with their real world implications.

Connections With Past Knowledge

          When friends and family have asked me how my Biochemistry class is going, most are a bit shocked at my emphatic response: I love it. I love this class precisely because of the connections it has created for me between the other areas of science I previously studied.
          I knew right away in our first class that this would be the case. We were asked to look at a titration curve and give our best guess interpretation of the information in front of us. Prior to this summer, I would have been clueless. Yet, as I studied for the MCAT exam last year, I found that I was teaching myself a great number of concepts; titration curves were one of these. So my interest was piqued during that first lecture when I realized this class will strengthen my knowledge of previous concepts, as well as tie them together across the multiple disciplines from which they were first introduced.
          Since then I have continued to connect our lessons in this class with previously encountered information. Most strikingly, Biochemistry has thus far seemed to provide a comprehensible bridge between lessons learned in Biology and those learned in Organic Chemistry. Biology was the study of life. Orgo was the study of chemistry related to carbon and its importance. More specifically, Orgo began to show how so much of our biological processes are dictated by the chemical rules and mechanisms covered in that course. I studied polarities, acids, bases, hydrolysis reactions, kinetics, activation energies, isoelectric points, peptide formations, and so much more. While many of the terms and molecules occasionally rang familiar bells from Biology class, the context in which they were discussed felt somewhat detached from their real world applications in living organisms.
          Yet in Biochemistry thus far, many of these concepts and molecules are being readdressed in ways which connect their Organic properties with the biological functions I had simply accepted at face value. Now, Biochem seems to be allowing me to connect dots between how things happen and why they happen, biologically and chemically speaking. For example, instead of simply memorizing curved arrow mechanisms, I have now seen how hydrolysis and saponification are used to break down triacyglycerols. Or for instance, instead of learning to recognize bonds with generic R groups, I have now seen that I am able to recognize bonds like phosphodiester linkages within essential DNA molecules.
          Learning how chemical properties dictate the biological functions which enable life to exist, has thus far fostered connections between my prior studies. Building these bridges between disciplines has furthered my comprehension of each topic. Synthesizing various disciplines into a cohesive understanding of biological systems has left me eager to discover what connections I will make next.

Thursday, March 1, 2012

PDB Molecule: Amyloid-beta precursor protein

The Amyloid-beta precursor protein (APP) is a rather large transmembrane protein, comprised of a sequence of 770 amino acids. APP is found on the surface of cells throughout the body and is responsible for many different physiological functions. Researchers believe APP has a central role in various processes, though the exact details of the protein's numerous functions are still being discovered. It is comprised of multiple domains which make the molecule flexible, and thus challenging to examine as a single intact protein. APP's fragmented form, however, garners the most attention as it is seen as a pivotal role player in Alzheimer's and other neurodegenerative disorders.



A healthy intact APP acts as a receptor on the surface of cells, capable of binding to various extracellular molecules. However, the protein is also subject to cleavage by secretases, a specific class of proteases. When APP is cleaved, peptide fragments are released. Release of one of these small peptides, known as the amyloid-beta peptide, is highly problematic. When amyloid-beta peptide is released, it changes shape and aggregates into long fibrils which then accumulate and form dangerous plaques. A buildup of these dense plaques on the surface of nerve cells leads to a disruption of normal function. The accumulation of plaque can slow nervous functions, lead to memory loss, dementia, and the onset of Alzheimer's Disease.

Though much has yet to be learned about the specifics of APP and it's fragmented peptides, they are the focus of current research. Scientists hope to target this protein and it's peptide fragments as possible sources of curing or treating debilitating neurodegenerative disorders such as Alzheimer's.

Thursday, February 9, 2012

What is Biochemistry?

     Biochemistry is the study of the molecular nature of chemical life processes. This encompasses numerous compounds, reactions, and chemical properties which collectively enable life to exist. Biochemistry examines the structures, identities, reactivities, and importance of various key molecules such as proteins, lipids, carbohydrates, and nucleic acids, to name but a few.

     The field of Biochemistry is inherently multidisciplinary, as it draws from numerous other fields of scientific study. Chemistry is the study of matter, including its composition, properties, structure, and interactions with other matter. Biology is the study of living organisms and systems. Molecular biology examines Biology in greater detail, focusing on the molecular basis of living organisms and systems. Similarly, genetics is the study of genes, chromosomes, and heredity, which are all crucial components of the living organisms studied in Biology.
   
     Biochemistry draws from and touches upon all four of the previously described disciplines. Many concepts from each of the aforementioned fields are examined in greater detail and different context. While Biochemistry examines biological concepts in great detail (similar to Molecular Biology), it does so with a chemical theme which enables bridges to be constructed between the studies of Biology, Chemistry, and Organic Chemistry. Synthesizing ideas from each of these fields into a collective study creates a discipline with a much broader scope than any one of them individually.