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!