Connections to Past Knowledge - Part III - The 3 Themes That Bind

There were actually more than three. However, the "ties that bind", at least to me, are these:

• Amino Acids
• Nucleic Acids
• Metabolism

In terms of how they connect to more than one topic, it's actually more than that. Everything interconnects. Understanding how proteins form amino acids, which lead to the formation of nucleic acids - that are based on sugars - and how we are put together genetically, which further lead to how we utilize sugars to live, are what it has been all about.

In Biology 413 we were introduced to amino acids as well as the processes of transcription and translation. Exploring these themes further in this course was instrumental in understanding how we are formed, and much of what we learned is similar to learning a new language. In many ways, understanding how amino acids are used to form nucleic acids can be thought of as learning "the language of life."

Much of what I knew before I came was what I have learned through the training I received up through Paramedic school. I was certainly familiar with the TCA cycle, but not to the degree I learned it in this class. One thing that occurred to me is that knowing how we metabolize the glucose we utilize is important in understanding how Diabetes affects that cycle.

The way the concepts were taught in this class were almost linear. Buy they really weren't; they all came together. At least in my mind they did.

Overall, it occurs to me that the grade earned isn't as important as the understanding that the information we acquired in this class as well as the concepts we learned about. I will try to keep that in mind in the future.

Glucose - How We Use It

I had to think about how I would explain to someone how glucose is used in our bodies. It's actually not as complex as one would think, and I will make an attempt to explain it in terms that someone who hasn't studied Biochemistry might understand.

We ingest glucose. It is the basic unit of potential energy that our bodies use. It can be in the form of a plate of pasta, a peanut butter and jelly sandwich, or a bowl of pork fried rice. For that matter, most of the foods we consume contain glucose in some quantity. When we eat that food product that contains glucose, a number of things happen. First, there is an enzyme in our saliva - salivary amylase - which initiates the breakdown of glucose for further processing.

Once the glucose is broken down, it is absorbed into the bloodstream, causing the blood glucose level to rise and triggering the secretion of insulin from the pancreas. Cells that need glucose have specific receptors attached to them - insulin receptors - which encourages the glucose to enter and be used.

Inside the cells, ATP - adenosine triphosphate - is used within the cell to store and release energy. There are two ways which this is accomplished: either anaerobic metabolism (without oxygen), or aerobic metabolism (with oxygen). Anaerobic metabolism is inefficient and produces small amounts of energy as compared to aerobic metabolism, which produces considerably larger amounts of energy. It is oxygen used by aerobic metabolism that makes the difference in energy produced. This is accomplished through a cycle of processes known as the Citric Acid Cycle, where through a series of  chemical reactions involving products, chemicals known as substrates, and enzymes which transform a given substrate in the cycle to another substrate. Ultimately, the cycle makes its way back to converting back to Citrate, which is an intermediate that precedes Citric Acid. This is done in the mitochondria, or the part of the cell that is involved in generating energy.

Because of the amount of energy that is generated in this cycle, it continues until the energy source - glucose - is completely used up.

Connections to Past Knowledge - Part II

Last semester in Biology 413 we were introduced to DNA/RNA transcription/translation. We have been covering it in this class since the return from spring break, but in considerably greater detail. Probably the most striking aspect of this, at least to me, is the level of detail we've seen it in. I understand that the detail is necessary to understand how it works, but I didn't realize there was as much to it as there is.

I'll use the following as an example: in Biology 413 the difference between prokaryotic and eukaryotic transcription and translation was mentioned in passing but never really discussed. In this course it is, and the amount of material is considerable. I had never heard of a Pribnow Box until one week ago. Now I know that it is one of the elements that makes up promoter structure in the process of synthesizing RNA. It is 10 boxes upstream from the TSS, or transcription start site, and is the first promoter element in the transcription process.

I know there is much more. And I have no doubt we will see more before this semester ends.

Website of Interest

I found a site that I thought was both interesting and potentially useful as a reference. It is The Medical Biochemistry Page, hosted by the Indiana University school of medicine. The content of the site is as a sort of reference library; it has links to pages which discuss specific subjects. For example, some of the pages are titled, " Basic Chemistry of Amino Acids", "Thermodynamics Review", "Sphingolipid Metabolism", and "The Cell Cycle", to name a few. I've looked at all of these pages, and their content is comprehensive and understandable.

What is available to the public is a subset of all of the material on the site. They offer a subscription service to access the entire site - rates are published. Whether or not I decide to subscribe to this site remains to be seen, but I have to be honest and say that from what I've seen it might almost be worth the investment.

Connections to Past Knowledge

I had a question about a specific clinical test last week and its relationship to the material we'd been discussing in class. In the previous lecture we'd learned about multi-subunit proteins with respect to Quarternary structures. In the lecture, multiple types of polymers - dimers, trimers, and tetramers - are said to be common. When I saw the term "dimer", it made me think of a clinical test that is run to rule out pulmonary embolism: a d-dimer. It is actually used in a number of different situations, including deep vein thrombosis (DVT) detection, and in the presence of stroke.

The test itself measures the level of Fibrin degradation. Fibrin is a non-globular protein that is involved in the clotting process - to actually actively work, Fibrinogen is converted to Fibrin by Thrombin, an enzyme involved in the clotting process.

A high Fibrin level usually indicates that further testing be done to determine whether or not a thrombus or embolus is present. Unfortunately, the d-dimer test itself is not always accurate. One of the problems with it is that conditions exist where false levels can be detected for a number of reasons including genetic makeup, presence of statins in the blood, and age to name a few. One condition where true high levels exist, however, is in a situation where the clotting cascade is behaving in such a way that its ability to produce Fibrin (from Fibrinogen, its precursor) is hyperactive.

In addition to function in clotting, Fibrin is also involved in platelet aggregation - its role here is in the signaling process of producing a hemostatic plug.

It was a "light-bulb" moment and I was surprised that I was able to make a connection to this from material being discussed in the classroom.

PDB Explorer Topic - Anthrax

This blog entry assignment is to go to the PDB Explorer website, find a protein that is of interest, and briefly describe it.

The protein I found for this entry is the Anthrax toxin. Its PDB identifier is 1ACC, and it is produced by gram-negative Bacillus anthracis bacterium. The toxin is stored in spores which is released when the spores are disturbed or agitated in some way. It is made up of three proteins including a Protective Antigen (PA), an Edema Factor (EF), and a Lethal Factor (LF) . The PA is what delivers the toxin to cells that are being targeted. Additionally, it is broken into four domains containing 735 residues. Each of the domains is responsible for a specific characteristic task with respect to the mechanism of delivering the toxin into the targeted cells.

Because of the fairly rapid delivery of toxins due to the architecture of the protein, it is considered a primary threat as it can be used in the production in a biological weapons system.

Anthrax Protecttive Antigen - Biological Assembly
Retrieved from  http://www.pdb.org under Fair Use guidelines

References:

Froude, J., Thullier, P., & Thibaut, P. (2011). Antibodies Against Anthrax: Mechanism and Clinical      Applications. Toxins, 3, 1433-1452. doi:10.3390/toxins3111433

Helgason, E., Okstad, O.A., Caugant, D., Johansen, H.A., Fouet, A., Mock, M., Hegna, I., & Kolsto, A. (2000). Bacillus antrhacis, Bacillus cereus, and Bacillus thuringiensis - One Species on the Basis of Genetic Evidence. Applied and Environmental Microbiology, 66(6):2627. doi:10.1128/AEM.66.6.2627-2630.2000.

What Is Biochemistry, Anyway?

This is the first of what will be a significant number of questions we will answer over the course of the semester. Personally, I like this format; it lends itself to be able to expand statements a bit more broadly than in a more formal format. Besides, in this format, readership potentially is wide open if the author wanted that.

A strict definition of the word biochemistry, according to dictionary.com, is "the science dealing with the chemistry of living matter." The World English Dictionary further defines it as "the study of chemical compounds, reactions, etc., occurring in living organisms." If you consider both of these definitions in the context they are presented in, they are obviously (I think) both technically correct. But it can be considered in finer detail; most science doesn't occur in a vacuum, and to consider what biochemistry is, and why it is studied, it must be looked at in the context of other fields of study within the sciences. Specifically, its differences with other scientific disciplines need to be considered.

Comparisons are always difficult because any number of people will have differing views as to what something is or what it is not. In looking at differences between the disciplines I have found a considerable number of differing views as to what they are and what they are not. I've done my best to parse them out so that I could form my own understanding of the differences I'll talk about. So, here goes.

First, Biochemistry versus Biology: biology is concerned with the study of organisms, plants and animals alike. Biochemistry is the study of the chemical processes and reactions within those organisms the biologist studies.

Molecular Biology, on the other hand, is the study of cells within an organism. Both the structure of the cell as well as how the cell functions is the concern of the molecular biologist. This goes back to something taught in the first semester of general biology, a concept known as "The Central Dogma of Molecular Biology." I remember thinking, "there is a dogma to this?" But it's actually not a horrible concept; it is the manner in which sequences (RNA, DNA, and proteins, specifically) are copied, transcripted, and translated. How this differs from biochemistry is that molecular biologists are more interested how these processes occur but they are not concerned as much with the chemical underpinnings of the processes themselves. That is the domain of the biochemist.

The same can be said for the study of genetics; a geneticist's interest lies in how organisms differ, in terms of their genetic makeup - the ATGC's of DNA and AUGC's of RNA. Further, geneticists look at how those differences in genetic makeup affect survivability among organisms and the species they come from. A biochemist looks at how the amino acids and protein structure that make up DNA and RNA function properly.

In many ways the job of a biochemist can be compared to that of a software engineer who develops the low-level code for a given computer architecture - the firmware. Without firmware, computers won't operate. And software without hardware is an absurd concept if you think about it; I'm not suggesting that by using his analogy either biology or chemistry is absurd, but I am saying that without the study of biochemistry, our understanding of life, like the computer system without a base set of instructions to function, would be incomplete.