Monday, February 27, 2012

Find an interesting Biochemistry Website

http://themedicalbiochemistrypage.org/index.php

This website is a teaching website geared towards the medical and health sciences student that provides an approach to the biochemical view of the normal human physiological processes as well as those that are involved in disease.  For example, the reader can access the page on Glycolysis: Regulating Blood Glucose and learn about the normal biochemical process involved in the basic digestion of starches and sugars, the oxidation of glucose for energy and the process of blood glucose level regulation.  From that same home page, the reader may access information on diabetes mellitis; a disease of blood glucose regulation; the different possible types and an explanation of the pathophysiology involved.

The medical biochemistry website is a great tool for biochemistry connections for those entering the medical field and studying the health sciences.  It is easy to use and the topics covered are conveniently listed on the front page.  The majority of the site's information is accessible without a paid subscription.  Glossaries for medical/clinical terms and abbreviations are provided for the student and a clinical lab data section offers normal value ranges for blood analysis data.

Thursday, February 23, 2012

What knowledge have you connected with past knowledge?


Biochemistry, by its very definition, bridges together various scientific disciplines.  Put simply: biochemistry bridges the study of the physical science of chemistry that explores the properties, interactions and energy between particles of matter with biology and its studies of living organisms and vital processes.  For a student with a fair amount of studying in both areas, biochemistry offers a chance to reflect and make many connections to concepts learned before, and to see how the scientific disciplines are bridged together, for a more complete understanding.

Thus far in this course, the most prominent high level connection I’ve made goes back to Anatomy and Physiology:  form always follows function.  Throughout our study of Human Anatomy and Physiology this concept is ground into our minds and remains the guiding principle for the study of all systems of the human body, from the high level of body systems, right down to the microscopic human cell.  We and our many parts are designed to carry out tasks in the most efficient manner to ensure the propagation and survival of the human species.  Biochemistry continues our studies with this same guiding principle, but at a closer angle- one that looks microscopically at the human cell and its functions and goes even farther to study the structure and interactions of the molecules that make up human tissue.  We study the structure of the various molecules involved, how they interact with each other and what function that has to human life.

For example, we have looked closely at hydrogen bonds between water molecules.  This is a simple way to view and understand these interactions that we then viewed in a much more complex protein structure.  We learned that these bonds are very important in determining the secondary structure of proteins; they are what hold the protein chain in helical arrangement, or pleated sheets, when the chain doubles back on itself or between two chains.  We have seen that the structure of these proteins is imperative to their function and the misfolding of the chains can cause these molecules to lose basic properties that allow their biological function:  for example they may misfold in a way that disrupts hydrophobic interactions, exposing the hydrophobic portions of the molecule which ultimately causes them to lose their solubility in the aqueous confines of the cell.  Aggregating together, they form a harmful substance, as is the case with the plaques associated with Alzheimer’s Disease.  Thus, hydrogen bonds, hydrophobic interactions and other inter-/intra-molecular interactions at play in the protein structure show a great example of how changing the structure and chemical interaction at the molecular level can have devastating impact on the function of anatomy at the systemic level that is studied in Human Anatomy and Physiology.

Another example of connection through biochemistry topics is that of enzymes.  In general chemistry we learned about catalysis and its effect on the free energy of activation.  In biochemistry, we are taking this chemical knowledge and seeing how it applies to proteins that we studied at a very high level in Anatomy and Physiology: enzymes.  We are now able to see the chemistry behind the enzymatic activity that is so incredibly vital to life processes and understand how and to what extent enzymes catalyze vital reactions.  The chemical structure and interactions at the enzyme active site give us a clear “how” to the process that we only touch upon in A&P.  The chemical structure or form shows us the “how” enzymes work, and the interactions and free energy of activation shows us the “why” these proteins provide the vital functions they do to carry out the processes and reactions of life that would otherwise occur way too slowly.

Through its connection of chemistry and organic chemistry fundamentals with their application to the molecules of life and function, biochemistry shows us how it all comes together, making sense of a multitude of previously introduced concepts.  I look forward to being able to see the rest of the connections that will unfold throughout this course.

Thursday, February 16, 2012

Find a protein using PDB explorer- describe your protein, including what disease state or other real-world application it has.


Protein:  3DSF 
Anti-Osteopontin Antibody 23C3 in Complex with W43A Mutated Epitope Peptide

This protein is an antibody associated with an extracellular linking protein called osteopontin that has been linked to the auto-immune disease Rheumatoid Arthritis.  This antibody-eptitope peptide complex is the foundation of hopeful treatment for patients suffering with this auto-immune condition that consists of inflammation and damage of the body’s synovial joints by the immune system.
Patients with Rheumatoid Arthritis have greater than normal amounts of osteopontin present in their synovial tissue.  It has been shown experimentally that osteopontin plays a role in the pathogenesis of RA: one that recruits inflammatory cells through chemotactic action, bringing more immune cells to the synovium, increasing inflammation and ultimately causing more damage to the joints.  The use of this antibody/epitope peptide protein complex may offer therapeutic relief for RA patients in the development of drug treatments based on the binding site to osteopontin, to block its chemotactic activities and reduce T-cell responses, which in turn will decrease the amount of inflammatory cells and damage to the joints.  Inclusion of the specific epitope offers an additional range of possibilities for the development for new drugs to treat RA disease.

Primary Structure:
A total of 441 residues are found in this protein complex.
Secondary Structure:
This antibody/epitope peptide complex consists of mainly beta sheets with a small percentage of helices and a short peptide from the osteopontin protein.
Tertiary Structure:
The forces and interactions involved in 3DSF determine its structure as a globular protein.
Quarternary Structure:
3 chains make this protein complex a trimer.  Typically antibodies exist as tetramers, containing 4 very flexible chains: two long, heavy chains and two short, light chains.  However, the flexible nature of these globular proteins makes it extremely difficult to study them intact.  The specific structure for 3DSF contains a heavy chain (H), a light chain (L) and a peptide from osteopontin:
Chain H:  Fab fragment of anti-osteopontin antibody 23C3, Heavy chain
                                5% helical (4 helices; 12 residues)
                                48% beta sheet (21 strands; 104 residues)
Chain L:  Fab fragment of anti-osteopontin antibody 23C3, light chain
                                3% helical (2 helices; 7 residues)
                                49% beta sheet (21 strands; 106 residues)
Chain P:  Peptide from osteopontin (12 residues)
Much of the immune response and attack of the synovium in Rheumatoid Arthritis is still not completely understood and medications that have historically been used to treat this autoimmune condition can be harsh and often have many undesirable side effects.  Recently there has been a surge of research into the mechanisms involved in the pathogenesis of RA and other autoimmune diseases, offering a promise of more effective biological treatment.  It is clear that osteopontin plays a role in RA and several other autoimmune conditions.  The development of this protein complex may offer new potentially more effective and less harsh therapeutic possibilities to those who suffer with RA.


For additonal information:

Tuesday, February 7, 2012

What is Biochemistry, and how does it differ from the fields of Genetics, Biology, Chemistry and Molecular Biology?


Biochemistry is the study of the chemical structures and functions of the molecules of life, the vital processes occurring in living organisms and the roles of biomolecules in these processes.  Biochemistry provides a view of biomolecules at the chemical level and considers their chemical structure and behavior as determining their functions in life processes.  It is a scientific discipline largely concerned with metabolism: the catabolic processes employed to extract energy and the anabolic processes to build the vital molecules of life.  It is a discipline of biological and chemical sciences that intricately overlaps multiple scientific disciplines, including genetics, biology, chemistry and molecular biology.

Biochemistry is a branch of biology; the science that studies living organisms and vital processes; as it studies the very molecules of life.  However, it branches off from biology with its consideration of the chemistry of the molecules of life.  Biochemistry takes into account the chemical structure of biomolecules and considers the impact of this structure and chemical interactions in its study of their function and processes.  The physical science of chemistry focuses on the structure, properties and interactions of all particles of matter and the energy between them.  Thus, from this perspective, biochemistry is a discipline of chemistry also, differentiating from it by its roots in biology and its specific focus on biological matter and processes.

Genetics; the science of genes, heredity and variation in living organisms; is also very closely linked to biochemistry.  The structure and function of the biomolecules DNA and RNA are considered heavily in biochemistry, as they carry the code for construction of other biomolecules.  However, genetics takes a different path in its study, focusing mainly on the structure of the gene in the context of an organism, how that gene is expressed and ways in which its expression may be halted or altered.  This is a higher level view than the biochemistry platform, which studies these macromolecules and their structures for the purpose of understanding their function to the biological processes of an organism.  Biochemistry is more concerned with what proteins these molecules code for and create, the process by which they accomplish this, and what function these molecules serve in basic biological function.

The “lines” defining the different areas of biochemistry and molecular biology appear to be even more blurred as molecular biology also takes a close look at biological activity at the molecular level and studies the interactions of the systems of cellular function.  Like biochemistry, molecular biology considers the structure of the molecules of life and how they function in the biological processes that are necessary to life.  However, its focus gravitates more to the study of genetic origin, transcription of genetic material, and its translation to the molecules of life and their cellular functions, while biochemistry focuses more on nutrition, metabolism and biological functions at the molecular level.  Molecular biology has its roots firmly grounded in biochemistry and genetics and has rapidly become any area of great interest and study; one that is so vast that it has required a distinction from other disciplines as its own entity and area of study.

One must note that defining the differences between these disciplines may be essential to understanding their functions and purpose in the scientific world, however, each of these disciplines is interwoven with the next, each reaching for further understanding as it pulls knowledge and connection from the others.  In many ways, biochemistry, genetics and molecular biology have no concrete defined lines between them and overlap greatly.  Perhaps the best way to understand it is by the concept of perspective- genetics coming from the perspective of understanding the gene and its expression, biochemistry from the perspective of studying the structure of biomolecules and how this determines their function in biological processes and metabolic processes, and molecular biology from the perspective of studying the processes of transcription and translation of genetic material into proteins and the molecules of life.  Each perspective offers more discovery and, when taken together, a more complete understanding of the very structure and function of life.

Friday, February 3, 2012