Tuesday, April 30, 2013

Famous quote (21)

“Science without religion is lame, religion without science is blind.” - Albert Einstein

Sunday, April 21, 2013

Cellular respiration - an overview

Today I will dedicate a post to some general considerations about cellular respiration. This process occurs in the mitochondria More precisely, in the mitochondrial inner membrane. To put it in a simple way, it is an oxidation-reduction process that involves the transport of electrons, from NADH and FADH2 to oxygen. In fact, it is mainly because of this process that we need to breathe oxygen. During the process, the O2 molecules are reduced to H2O, which is the main reason for us to breathe out water vapor. Thus, in fact most of our pulmonary respiration is not more than a consequence of our cellular respiration!
But back to the cellular respiration process... The electrons are received and transported over four complexes, designated I, II, III and IV. These complexes are not more than sets of electron transport proteins, many of which with cofactors specialized in the transport of electrons, such as iron-sulfur centers, heme and flavoproteins. A key element in this process is the presence of transition metals (iron and copper, for example) because, due to the fact that they can oscillate between two oxidation states, they are able to temporarily capture or donate electrons.
For electrons to pass from complex I or II to complex III, there is a lipophilic molecule that will carry them, which is called ubiquinone. For the electrons to move from complex III to IV there is an intermembrane space protein that carries them, designated cytochrome c.
As the electrons move along the complexes, in some of them ther will be a coupled process, which is the proton (H +) pumping from the matrix to the intermembranar space. That means, it will be created a H+ gradient, designated electromotive force , which will accumulate enough energy to drive ATP synthesis via a process called oxidative phosphorylation. The intervening in this process is the mitochondrial ATP synthase.
In future posts I will devote some attention to a detailled explanation of how cellular respiration works...

Wednesday, April 17, 2013

Music about hormones (epinephrine)

Simon and Garfunkel have immortalized many songs, among which is the famous "The sound of silence". Dr. Ahern adapted this beautiful music and created a song about the hormone apinephrine. You can download it in www.davincipress.com/metabmelodies.html.
The Tao of Hormones

Biochemistry my friend
It's time to study you again
Mechanisms that I need to know
Are the things that really stress me so
"Get these pathways planted firmly in your head,"
Ahern said
Let's start with ep-inephrine

Membrane proteins are well known
Changed on binding this hormone
Rearranging selves without protest
Stimulating a G alpha S
To go open up and displace its GDP
With GTP
Because of ep-inephrine

Active G then moves a ways
Stimulating ad cyclase
So a bunch of cyclic AMP
Binds to kinase and then sets it free
All the active sites of the kinases await
Because of ep-inephrine

Muscles are affected then
Breaking down their glycogen
So they get a wad of energy
In the form of lots of G-1-P
And the synthases that could make a glucose chain
All refrain
Because of ep-inephrine

Now I've reached the pathway end
Going from adrenalin
Here's a trick I learned to get it right
Linking memory to flight or fright
So the mechanism that's the source of anxious fears
When I make ep-inephrine

Saturday, April 13, 2013

Famous quote (20)

The saddest aspect of life right now is that science gathers knowledge faster than society gathers wisdom. (Isaac Asimov)

Tuesday, April 2, 2013

Regulation of the Krebs cycle

The Krebs cycle plays a central role in our metabolism. In all the classes I give about metabolism, the Krebs cycle is present...
As I mentioned in previous posts, this process is composed by 8 steps, 3 of which are catalyzed by regulatory enzymes. These enzymes are citrate synthase (1st reaction), isocitrate dehydrogenase (3rd Reaction) and alpha-ketoglutarate dehydrogenase (4th reaction).
In this post I will talk a little about the main activators and inhibitors of each. As you will see, there are many modulators that are common to more than one enzyme, which makes life easier for those who have to study this metabolic pathway. :)

Citrate synthase:
Succinyl-CoA - it is an intermediate of Krebs cycle. More specifically, it is the 4th intermediate of Krebs cycle, that means, it is formed in a reaction after the reaction that we are considering. So if we have an accumulation of intermediates formed in further reactions, it makes sense that these may inhibit the initial reactions of the pathway in question, in this case the first.
Citrate - it is the product of the reaction, so it makes sense that it might inhibit its own synthesis.
ATP - the Krebs cycle is a catabolic pathway, ie, its main goal is to produce energy (ATP). If the cell already has energy, the process is inhibited.
NADH - The reasoning is equivalent to that made for the ATP. That is, the NADH has a high energy potential, since in cellular respiration it can lead to the production of ATP, therefore it is logical that NADH functions as an inhibitor of Krebs cycle.
Long Chain fatty acid-CoA - it is not completely understood the inhibitory role of the long chain fatty acids in the Krebs cycle, but it is believed that this property is related to the fact that they behave as detergents because they are amphipathic compounds consisting of one polar part (carboxylic group) and one part apolar part (hydrocarbon chain). Oleic acid (18 carbons and one double bond at carbon 9) appears to be the major fatty acid inhibitor of citate synthase.

ADP - ADP signals an energy deficit in the cell because it is produced when ATP is spent for energy. So it makes sense that it activates the Krebs cycle, because the main objective of this pathway is the production of energy.

Isocitrate dehydrogenase:

Succinyl-CoA - the reasoning that was made for the citrate synthase applies in this situation.
ATP - the reasoning that was made for the citrate synthase applies in this situation.
NADH - the reasoning that was made for the citrate synthase applies in this situation.

ADP - the reasoning that was made for the citrate synthase applies in this situation.
Ca2 + (muscle) - as I mentioned in a previous post, about the regulation of pyruvate dehydrogenase complex, Ca2+ is an intracellular messenger whose concentration increases during muscle contraction. Therefore, in this context contracting cells will require energy, so catabolic processes and, in particular, the Krebs cycle, is activated.

Alpha-ketoglutarate dehydrogenase:
Succinyl-CoA - it is the product of the reaction so, it makes sense that this molecule may inhibit its own synthesis.
ATP - the reasoning that was made for the citrate synthase applies in this situation.
NADH - the reasoning that was made for the citrate synthase applies in this situation.

Ca2 + (muscle) - the reasoning that was made for isocitrate dehydrogenase applies in this situation.

I am back... )

After a period in which I was not able to post anything in th blog, due to personal and profesional reasons, I am back. :)
During this day I will return to the posts!