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The next topic on the agenda for Biochemistry I was that of enzymes. It served to edify the student of the molecular basis for the feasibility and rate of biological reactions, and their impediments. The classification of enzymes into oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases was elaborated upon into the EC context. Definitions of cofactors and coenzymes and thier importance to enzymatic function was done. Different classes of inhibitors and their effects on graphical representations and measurable parameters of a reaction proved to an interesting section and an appreciation for the limitations of biological reactions was attained. Structure of active sites illustrated the basis for the hypothetic models of enzyme specificity, which include Fischer’s lock and Key hypothesis, Koshland’s induced fit hypothesis, the non-productive binding model,strain and distortion and transition state stabilization.
“Snake Venom Protein Paralyses Cancer Cells”
According to an article read in the February 2013 issue of National Geographic magazine, titled “The Healing Power of Venom” the infinite medicinal possibilities of venom proteins in treating debilitating diseases has redefined the boundaries of where scientists go to search for such compounds. In fact, venom usage to treat afflictions has been documented in second century Sanskrit texts, indicative of the esteem it held amongst ‘healers’ both ancient and modern. Science is lending overwhelming credibility to the applications of venom, and this article inspired me to delve a bit deeper into the toxic world of venom; this journal review is based on research into the cancer fighting properties of snake venom proteins as elaborated on in an Oxford Journal publication.
Estimates tentatively reveal an astounding twenty million venom toxins waiting to be screened for medicinal properties; venom spread out all over the Animal Kingdom, including snakes, poisonous snails, gila monsters, arachnids, poisonous frogs amongst others. According to this journal (see reference below), a component of snake venom has been found to inhibit cancer cell mobility. Central to this discovery is the venom protein known as contortrostatin,extracted from the southern copperhead(Agkistrodon contortrix contortrix). It was found to be a disintegrin; these compounds are antagonistic to integrins which are transmembrane receptor proteins which bind extracellular matrix and provide a route for cellular migration. Cancer cells possess integrin proteins in their membranes, which enable migration upon tumour dissemination ; the primary integrin is αvβ3. Integrins are able to bind ligands that leads to ‘focal adhesion’ whereby ligand attachment signalling leads to clustering of the integrins at a particular site which then leads to extracellular matrix adhesion.
Contortrostatin was found to limit cellular migration by binding to integrin receptors and interfering with their ability to adhere to extracellular matrix. It also was inhibitory upon the extracellular proteins fibronectin and vitronectin, as well as limiting tumour cell migration, dissemination and angiogenesis(vessel formation which would provide circulatory attachment for the tumour). Signal disruption conveyed by contortrostatin was due to crosslinking of αvβ3 integrins, leading to defective focal adhesion and cytoskeleton manipulation.
As an aside, other potential venomic medicinal indications include the isolation of a peptide from the Eastern green mamba(one of the deadliest snakes in the world) known as cenderitide, which was found to have a pharmacological basis in fibrosis reduction, blood pressure lowering and kidney shielding. Another is the compound extracted from Gila monsters known as exenatide which maintains blood sugar levels. A neurotoxin attained from the giant deathstalker scorpion has use in ‘tumour painting’ due its ability to attach to brain cancer cells, facilitating ease of identification of good cells from bad cells at a tumour’s growth edges.
Venom, viewed as grisly, pain –inducing, deadly substances, and perhaps rightly so, has however, found a niche in the treatment of debilitating diseases. The research into their potential and applications continues unabated, in light of their proven worth so far into various affliction remediation. Indeed, the molecular biology impetus behind the understanding of venom and its mechanism of action, as well as the chemical basis for isolation and modification of venom-derived compounds represents an exciting foray into the world of battling disease.
References:Finn, Robert. “Snake Venom Protein Paralyzes Cancer Cells” 2013. Accessed April 13th 2013. http://jnci.oxfordjournals.org/content/93/4/261.full
1) 1) How is the alpha-helix stabilized?
a) Hydrogen bonds between peptide bond carbonyl oxygens and amide hydrogens
b) Disulphide bridges
c) Hydrophobic interactions
d) Electrostatic interactions between oppositely charged ions
e) Hydrogen bonding between hydroxyl groups and water
2) 2) What does the term ‘epimer ‘ refer to?
a) Presence of chirality
b) Difference in configuration around 1 carbon atom
c) A disease affecting carbohydrate metabolism
d) An oligopeptide consisting of 3 sugars
e) Presence of an achiral carbon atom
3) 3)What molecules is glycogen synthesized from?
d) Fructose and glucose
4) 4) D-galactose and D-mannose are
e) Ketose sugars
5) 5) Which of the following is a ketose sugar?
6) 6)Which is most likely to affect the 3 –dimensional conformation of a protein?
a) Insertion of proline amino acids
b) Substitution of valine for leucine
c) Dehydrogenation of carboxy terminal amino acid
d) Oxidation of amino terminal amino acid
e) Dynamic electron dispersal in bonds
7) 7) The presence of a non-competitive inhibitor
a) Increases both Vmax and Km
b) Decreases Km
c) Increases Km and decreases Vmax
d)Decreases both Vmax and Km
e) Decreases Vmax
8) 8) Km is equal to
a) Numerically, the substrate concentration at which maximal velocity is half
b) ½ Vmax
c) –log pKa
d) Enzyme concentration + substrate concentration
e) Enzyme concentration/substrate concentration
9) 9)Which of the following is a prokaryote?
10) Which is responsible for mobility?
b) Golgi apparatus
e) Smooth endoplasmic reticulum
First woman to be awarded the Nobel prize in Medicine or Physiology. She was an American biochemist whose pioneering work involved the discovery of the mechanism by which glycogen is broken down in muscle tissue to form lactic acid and resynthesized in the body and stored as a form of energy. This cycle is known as the Cori cycle as such.
Reference: Accessed April 8th 2013. http://en.wikipedia.org/wiki/Gerty_Cori
Amyloidosis results from the abnormal deposition of insoluble proteins in various tissues. The insoluble protein aggregates are known as amyloids and are caused dy disruption of the protein’s secondary structure causing the insolubility and makes them unable to be degraded by proteolysis(the beta sheet structure is affected and is hydrophobic forming clusters which are stabilized by glycosaminoglycans and serum amyloid P).