Glycolysis Wordle

Reflection XVI: Glycolysis I

Hey guys,

Today we begin glycolysis! YAYYY!!!

For this reflection,  I have posted biochemjm’s (hokage’s) first video above.

 

Summary

Glycolysis

In summary, a single glucose molecule in glycolysis produces a total of 2 molecules of pyruvic acid, a net gain of 2 molecules of ATP, 2 molecules of NADH and 2 molecules of water.

Although 2 ATP molecules are used in steps 1-3, 2 ATP molecules are generated in step 7 and 2 more in step 10. This gives a total of 4 ATP molecules produced. If you subtract the 2 ATP molecules used in steps 1-3 from the 4 generated at the end of step 10, you end up with a net total of 2 ATP molecules produced.

I also found this animation of glycolysis to be particularly helpful 😀

http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter25/animation__how_glycolysis_works.html

Hope you guys learnt stuff 🙂

Published Paper II: Inhibitor… Yay or Nay?

Reference

Ito Takahiro, Bryan Zimdahl, Tannishtha Reya. 2012. “aSIRTing Control Over Cancer Stem Cells.” Cancer Cell 21 (2): 140-142. Accessed March 8. http://dx.doi.org/10.1016/j.ccr.2012.01.014

Cancer stem cells lie at the root of chronic myelogenous leukemia (CML) and mediate its continued growth. The high resistance of these cells to therapies has lead to the inability to eradicate the disease. Chronic Myelogenous Leukemia (CML) begins in hematopoietic stem cells. A kinase inhibitor, imatinib mesylate, revolutionized the treatment of the cancer by keeping the symptoms and spread of the cancer at a controlled rate, however this treatment is far from the cure. This leads to a lifelong dependence on the drug, which increases the risk or relapse and progression of the disease. Also the drug is not effective against the advanced stages of the disease, which is when most people are diagnosed.

CML comprises of differentiated cells which are eliminated by the kinase inhibitors and undifferentiated cancerous stem cells that propagate the disease and remain unaffected by the drugs, hence persist despite drug therapy. Therefore to target the disease, it is crucial to identify the regulators required for CML cancer stem cell growth renewal thereby stopping CML growth. Further studies lead to the conclusions that the drug Sirtuinis, was an important control point in cancer stem cell production, and provided a strong indication of the metabolic pathway in cancer cell development. Basic translational work has identified several pathways critical to CML stem cell function and renewal. These studies have shed light on molecular mechanisms that protect and sustain CML cancer stem cells allowing them the evade imatinib mesylate.  Immediate transitional interest may be paid to some easily targeted mechanisms; however, strategies are currently being tested to find the effective and suitable suppressors of the cancer development.

Reflection XV: INHIBITION DUN DUN DAHHHHHHH X__X

INHIBITION!

INHIBITION EVERYWHERE!!!

Okay maybe I’m over reacting, but think about it. Imagine if you were an enzyme, minding your own business and BAM! some random molecule comes and changes you completely leaving you unable to function.

I mean it isn’t very nice especially if you’re a particularly helpful enzyme. Of course not all inhibition leads to this fate.

I guess it really is a perspective thing though. Because if you think about it,  the inhibition of enzymes may not seem nice from an enzyme perspective but what if that enzyme is catalyzing an unwanted or unnecessary reaction? The body actually utilizes a certain type of inhibition as a from of negative feedback to prevent the production of excess products and a waste of cellular reserves.

We ALL know where this is going, so I guess we should get right into it.

Enzyme inhibitors are molecules that interfere with catalysis by slowing down of halting enzymatic reactions. Inhibitors can affect enzymes either reversibly or irreversibly.

Inhibition

REVERSIBLE INHIBITION

Reversible enzyme inhibition does not permanently alter the enzyme and usually occurs when reversible inhibitors bind non-contently with the enzyme, resulting in four different types of reversible inhibition.

Competitive inhibition occurs when a competitive inhibitor is present. This inhibitor molecule, which is structurally similar to the substrate, competes for the active site of the enzyme by occupying it, forming an enzyme inhibitor complex and preventing the substrate from binding to the enzyme active site. This can be further analyzed via the following graph:

Lineweaver Burke Plot of Reversible Inhibition: Competitive Inhibition (Bliq. 2013)

In the presence of a competitive inhibitor V_max of the reaction remains constant, however, K_m of the reaction increases as it takes a higher concentration of the substrate to reach half the V_max. The effects if competitive inhibition can be lowered by increasing the concentration of substrate.

Uncompetitive inhibition, another type of reversible inhibition, occurs when  the inhibitor, which does not resemble the substrate, binds to a site distinct from the active site and binds only to the enzyme-substrate complex. This causes the V_max to decrease as a result of removing the activated complex and thus decreases K_m.This can be observed in the graph blow.

Lineweaver Burke Plot of Reversible Inhibition: Uncompetitive Inhibition (Bliq. 2013)

 

Mixed inhibition is the third type on reversible inhibition and arises from the presence of an inhibitor, that does not resemble the substrate, which binds to a site distinct from the active site on either the enzyme-substrate complex or the enzyme itself. Both V_max and K_m are affected. V_max is lowered while K_m increases. This can be seen in the graph:

Lineweaver Burke Plot of Reversible Inhibition: Mixed Inhibition (Bliq. 2013)

 The last type of reversible inhibition is noncompetitive inhibition which occurs when the binding of the inhibitor, which does not structurally resemble the substrate, to the enzyme reduces enzyme activity but does not affect the enzyme-substrate binding; therefore, as a result the extent of inhibition is dependent on the concentration of the inhibitor, i.e. as the concentration of the inhibitor increases the slower the rate of reaction. Hence in the presence of these inhibitors V_max decreases and K_m remains the same. This can be seen in the graph below.

Lineweaver Burke Plot of Reversible Inhibition: Noncompetitive Inhibition (Bliq. 2013)

           

IRREVERSIBLE INHIBITION

  Irreversible enzyme inhibition occurs when the inhibitor interacts with the enzyme and changes it chemically at the active site. This usually occurs by bonding covalently with the enzyme, destroying a functional group that is essential to ezymatic activity or by forming a particularly stable non covalent enzyme-inhibitor complex. 

Irreversible Inhibition

Welp thats all for now folks ^_^

Game Time!! (*_*)

Hey guys!

Alright you caught me… its more of an activity than a game

But it can still be fun right?

Here is an activity I came up with for us to learn those important definitions.

P.S. to enlargen  the pic just click on it. 

WHAT TO DO?

So the definitions are located on the left and the words defined on the right, all you need to do is match the correct words with its corresponding definition. Enjoy!! 

Reflection XIV: Isozymes ^_^

Hey Biochemians,

Today we’re going to look at isozymes. Although not gone into detail in the course, when I was checking the course outline, I happened to notice that it was one of the terms we needed to know.

Now before we walk into the exam not knowing,

or panicking,

I shall now briefly explain the fun and importance that is isozymes. ^_^

Isozymes (also known as isoenzymes) are homologous enzymes that catalyze the same reaction but differ in structure. The differences in the isozymes allow them to regulate the same reaction at different places in the specie. These enzymes differ in amino acid sequences and display different kinetic parameters as well as regulatory properties.

Isozymes are encoded by different genes and expressed in a distinct organelle or at a distinct stage of development. The purpose of these isomers is to allow fine adjustment of metabolism to meet the need of different development stages and help the different tissues and organs function properly depending on their physiology and in what kind of environment which they function. Hence these enzymes appear in specific regions of the body; differing in specifics organelles or tissues.

And that’s the generalization of isozymes.

Happy studing

Published Paper I: Fuel for Thought?

Reference

Powell J, Pollizzi K. 2012 “Fueling Memories.” Immunity 36 (1): 3-5. Accessed March 5,  http://dx.doi.org/10.1016/j.immuni.2012.01.003

The world with respect to biochemistry is constantly moving at alarming pace as a result of increasing technology, so too is the required learning and teachings of the subject. As such many assumptions are being cleared up and new theories discovered on a daily basis. The development and roles of T cells, responsible for memory of diseases, have been closely monitored in oncology studies to reveal that increases in metabolism play an integral role in the promotion of T cell activation. Activated effector cells are anabolic, utilizing glycolysis for ATP, whereas memory cells are catabolic, metabolizing fatty and amino acids as well as glucose while utilizing oxidative phosphorylation for ATP production. The study of T cell activation is quite imperative to understanding cancerous cells as the two have been recognized to be activated along similar methods. The understanding and study of these unique metabolic pathways is fundamentally important due to the fact that, even though these pathways lead to activation of T cells, in the absence of these reactions, T cells cannot function.

T-lymphocytes must employ pathways that facilitate their long term survival, however, must do so in a manner in which they can function as efficiently as possible. To do this the cells must respond quickly and with vigor, hence the bioenergetic limits of these cells are measured and compared. This is done observing the mitochondrial membrane potentials of the cells, which when in large amounts increased long term survival of the cells and provided energy for rapid and robust cellular activation. IL-15 promotes the generation of memory cells by promoting mitochondrial biogenesis and the expression of CPT1a, the rate limiting enzyme in FAO. Consequently, memory cells generate less toxic superoxide radicals, live longer, and generate increased concentrations of ATP. This suggests that targeting metabolic pathways effectively can control immunological responses and inhibition of specific pathways will hinder undesirable responses.

Reflection XIII: Inorganic Catalysts vs. Biological Catalysts

Hey guys 😀

Today I would like to reflect on the differences between inorganic catalysis and biological catalysts (enzymes).

Enzymes and inorganic catalysts both affect the rate of a reaction. The difference between the two is that, enzymes are largely organic in nature and are bio-catalysts.  Hence even though all known enzymes are catalysts, all catalysts are not enzymes. 

Here’s  a table which quite nicely sums up the basic comparisons.

Some things that I would like to add though to this are:

• Enzymes are much more efficient than inorganic catalysts as inorganic catalysts usually require high temperatures and/or high pressures for the reactions to be catalyzed, whereas in our bodies hundreds and thousands of catalysts exist and perform at average body temperature (35-37 degrees Celsius). 
• The catalytic power of enzymes is quite higher than that of inorganic catalysts.
• Inorganic catalysts can be poisoned, easily whereas organic catalysts are not easily poisoned.
• Enzymes are regulated, inorganic catalysts are not.

Yup that’s all for now folks.

MCQs Part II: Enzymes

Alrighty guys here we go again! Time to see how much we’ve learnt / need to learn on enzymes.

Here is the key. You use this key from A-E to answer the multiple answer questions. Got it?

A. I only is correct.

B. II & IV only are correct.

C. I, II, and III are correct.

D. All options are correct.

E. None of the answers shown are correct.

____________________________________________________________________________________

1.Which of the following statements is false

I. Enzymes increase chemical equilibrium.

II. Enzymes are biological catalysts that speed up chemical reactions by providing an alternative pathway with              a lower activation energy.

III. Activation energy is the minimum energy required for the reaction to occur

IV. The 3 distinctive features of enzymes are: catalytic power, specificity and regulation.

____________________________________________________________________________________________

2. A holoenzyme is

I. A complete catalytically active enzyme together with its bound coenzyme and/or metal ions.

II. A special coenzyme or metal ion that is very tightly or covalently bound to the enzyme protein.

III. A chemical component needed for enzymatic activity.

IV. Derived from vitamins, orgainic nutrients and are required in small amounts

___________________________________________________________________________________________

3. The transition state

I. has the highest energy arrangement of atoms.

II. is intermediate in structure.

III. is highly unstable.

IV. is a chemical species with significant stability, similar to reaction intermediate.

____________________________________________________________________________________________

4. Enzymes are:

I. biological catalysts

II. highly specific

III. classed according to the reactions they catalyze

IV. usually proteins, however some are made of RNA

____________________________________________________________________________________________

5. The types of reversible inhibition are

I. competitive inhibition

II. uncompetitive inhibition

III. mixed inhibition

IV. non-competitive inhibition

Enzymes Quote

“Enzymes are catalysts. They are transformative elements. They are truly an alchemical symbol of transformation. On a physical level, enzymes help to overcome digestive lethargy. On a spiritual level, enzymes help to overcome life’s ruts and setbacks – enzymes overwhelm spiritual stagnation… If you want things to change for you, if you want to attract and create beauty in your life, you have to do something different than you are doing now. If you desire a different destiny (destination) than relatives and friends who ended up dead broke or dead at the age of 65, then you must do something different now. Food enzymes make the difference.”

– David Wolfe, in “Eating For Beauty”.