Music about enzyme catalysis

This music is about enzyme catalysis and is an adaptation of the song Close to You.

http://www.mediafire.com/?omzv9utktseeodu

Catalyze
My enzymes
Truly are inclined
To convert
Things they bind
Turn the key
Covalently
Cat-a-lyze
 

How do cells

Regulate these roles?
Allo-ster-ic controls
Two forms, see
States R and T
Mod-u-late
 
Competing inhibition keeps
The substrates from the active site
They raise Km, but leave Vmax and shirk
While the non-competers bind elsewhere
And lift the plot made on Lineweaver-Burk

Other ways
Enzymes can be blocked
When things bind
Then get locked
Stuck not free
Tied to the key
Su-i-cide

Penicillin’s action stops
Peptidoglycan cross-links in
Bacterial cell walls in awesome ways
Beta lactam ring’s reactive site
Starts bonding with D-D-transpeptidase
 
So there are
Several enzyme states
Counteract-ing substrates
Now you see
Blocking the key
Regulates
 
Cat-a-lysts
Have to be controlled
Some get slowed
Put on hold
It's sublime
How the enzymes
(slow) Cat-a-lyze
 
ahhhhhhhhhhhhhhhhhhh - cat-a-lyzeahhhhhhhhhhhhhhhhhhh - cata-
lyzeahhhhhhhhhhhhhhhhhhh - cat-a-lyze

Music about enzymes

Here it goes a link to download another Metabolic Melody, this time about enzymes. It was base on the song Downtown.

http://www.mediafire.com/?w0gd96oo6ecpymg

Enzymes

Reactions alone

Energy peaks

Are what an enzyme defeats

In its catalysis

Enzymes

Transition state

Is what an enzyme does great

And you should all know this

Enzymes

Catalytic action won't run wild - don't get hysteric

Cells can throttle pathways with an enzyme allosteric

You know it's true

So when an effector fits

It will just rearrange

all the sub-u-nits

Inside an

ENZYME!

Flipping from R to T

ENZYME!

Slow catalytically

ENZYME!

No change in Delta G

(Enzyme, enzyme)

You should relax

When seeking out the Vmax though

There are many steps

Enzymes

Lineweaver Burk

Can save a scientist work

With just two intercepts

Enzymes

Plotting all the data from kinetic exploration

Let's you match a line into a best fitting equation

Here's what you do

Both axes are inverted then

You can determine Vmax and

Establish Km for your ENZYMES!

Sterically holding tight

ENZYMES!

Substrates positioned right

ENZYMES!

Inside the active site

Enzymes (Enzymes, enzymes, enzymes)

Could starve your cells to the bone

Thank God we all produce

Enzymes

Units arrange

To make the chemicals change

Because you always use

Enzymes

Sometimes mechanisms run like they are at the races

Witness the Kcat of the carbonic anhydrases

How do they work?

Inside of the active site

It just grabs onto a substrate

and squeezes it tight

In an

ENZYME!

CAT-al-y-sis

In an ENZYME!

V versus S

In an

ENZYME!

All of this working for you

(Enzyme, enzyme)
 

Glycolysis (enzymes of the payoff phase)

The payoff phase, as I mentioned earlier, concerns the whole of the last five reactions of glycolysis and allows the cell to obtain energy in this process. Here are some ideas on the enzymes of phase 5 payoff ...
6^th enzyme – Glyceraldehyde-3-phosphate dehydrogenase

This enzyme, often abbreviated to GAPDH, is presented in the form of a tetramer. Each subunit has about 35.9 kDa (331 amino acids) and shows how a molecule of cofactor NAD+. The subunits are designated by O, P, Q and R and are independent of each other. That is, each subunit catalyses the reaction without the intervention of others. As described in the post about the reactions of the payoff phase, the reaction catalyzed by this enzyme is a double one, involving an oxidation and an addition of a phosphate group. It is an enzyme that may be affected by the presence of arsenic in the body, causing the yield of glycolysis to become null. Its mechanism of action involves both a covalent catalysis and acid-base. To do this, it is essential the participation of cysteine ​​149 and histidine 176 for both types of catalysis, resectivamente. The substrate binds covalently to cysteine​​, forming a hemitioacetal. The laboratory level this enzyme is widely used (I also use ...) as a positive control techniques such as immunoblotting or RT-PCR, because in general their expression is constant in almost all cell types. So it is possible to determine changes in the expression of a certain gene or in the presence of a given protein by comparing it with the levels of GAPDH.

7^th enzyme – Phosphoglycerate kinase

This enzyme requires Mg²⁺ to make its catalytic activity. The name derives from the reaction of the enzyme in the reverse direction, which occurs during photosynthetic CO₂ fixation. It is responsible for the production of the first molecules of ATP in glycolysis. Its amino acid sequence has to be extremely conserved in different organisms. The monomeric enzyme is composed of two domains of equivalent size, which corresponds to half N-and C-terminal. The substrate (1,3-bisphosphoglycerate) binds to the first half, while ADP binds to the second. Presents a sequential kinetic mechanism in which catalysis occurs by a proximity effect.
8^th enzyme 8th – Phosphoglycerate mutase

The phosphoglycerate mutase is dimeric, with each of its subunits with about 32kDa. As the name implies, this is a mutase enzyme, ie, catalyzes the transfer of phosphoryl groups within a molecule. In other words, it changes the position of phosphoryl groups. In fact, the enzyme is phosphorylated (fosfoenzima is one), and will give up its phosphoryl group to the carbon of the substrate 2, resulting in an intermediate with two phosphoryl groups (2,3-bisphosphoglycerate). Only after this step, is that the phosphoryl group that was originally in the substrate (position 3) is removed, regenerating the initial form (phosphorylated) enzyme.

The phosphoglycerate mutase has three different isoforms (isozymes or isoenzymes), predominantly found in cardiac muscle, skeletal muscle and the third one in the other tissues.

9th enzyme – Enolase

The enolase is a dimeric metalloenzyme, and each subunit has about 40-50 kDa. These subunits have an antiparallel orientation, interacting with each other via two salt bridges, involving an arginine and a glutamate each. The N-terminal domain of alpha-3 subunit has four helices and beta sheets. The C-terminal domain has two beta sheets and two alpha-helices, and it ends with a barrel consists of beta sheets and alpha helices alternate. The two Mg²⁺ ions required for catalytic activity are critical in neutralizing negative charges. This enzyme has a pH optimum of about 6.5, and can also be called fosfopiruvato dehydratase. It was initially discovered in 1934 by researchers Lohmann and Meyerhof. As with the enzyme before the enolase also has three different isoforms, of which one is predominantly found in muscle tissue, the other in neurons and the third one in the remaining parts of the body.
The enolase is inhibited by fluoride ion, and this fact is exploited, for example, when collecting blood samples for analysis. In this case, when it is important to inhibit glycolysis (to keep unchanged the concentration of serum glucose), blood can be collected in tubes containing fluoride.
10^th enzyme – Pyruvate kinase

This enzyme is responsible for the second ATP production in glycolysis and is the third regulatory enzyme of this pathway. It needs the presence of two metal ions: K⁺ and Mg²⁺ (or Mn²⁺). It has four different isoforms, one located predominantly in the liver, another in red blood cells, the other in cardiac and skeletal muscle and brain and the latter is mainly found in fetal tissues. It is a tetrameric enzyme, each subunit has about 500 amino acids.

Main bibliographic sources:

- Voet D, Voet JG, Biochemistry, Wiley

- Nelson DL, Cox MM, Lehninger - Principles of Biochemistry, WH Freeman Publishers

Glycolysis (enzymes of the preparatory phase)

As I have already mentioned on other posts, glycolysis is composed by 10 biochemical reactions catalyzed by enzymes all different. Today I dedicate this post to some information on the enzymes of the preparatory phase.
1^st enzyme - Hexokinase
This enzyme, present in all our cells, has different isoforms present in our body and is the first point of regulation of glycolysis. In general, regardless of the isoform considered, its mass is about 100kDa. It is an enzyme that can be structurally divided into two halves with plenty of homology, the N-terminal half and half C-terminal. Because of this characteristic, it is thought that the gene for this enzyme may have arisen by duplication of an ancestral gene. The 3D structure of hexokinase can be compared to the shell of a bivalve...

There are four major isoforms of hexokinase (I-IV), and the fourth may also be called glucocinase (or hexokinase D), and is found primarily in the liver. Glucocinase The kinetic properties and regulatory features significantly different from other isoforms. The hexokinase I-III have a very high affinity for glucose (Km for glucose is about 0.1 mM), and to a normal concentration of glucose (4-5 mM) the enzyme is saturated with substrate. That is, the amount of available substrate is sufficient for the enzyme to function at its maximum speed. On the other hand, glucocinase presents a much higher Km (10 mM), which means that under normal conditions the enzyme is far from saturated with substrate. Probably at this point you will ask: "What's the point of this? It should be much more advantageous to have an enzyme to function at its maximum speed!" The answer to this question is very simple ... The function of glucocinase is to produce glucose-6-P which is then diverted mainly to the synthesis of liver glycogen. Thus, it only makes sense we have a lot synthesize glycogen when glucose availability is high. Therefore, the glucocinase will only start operating at a higher speed if there is an increase in the substrate availability. In other words, unlike what happens with the other hexokinase, when higher the concentration of glucose increased the speed of action of glucocinase.

The main substrate of hexokinase is D-glucose, but can also use other substrates such as hexoses, such as D-fructose and D-mannose. However, the value of Km for these substrates is higher, ie, the enzyme can use them but has less affinity for the same. This situation occurs mainly caters for hexokinase I-III, and the glucocinase is more specific for glucose.

The mechanism of action of hexokinase is called the Random Bi Bi, in which the enzyme forms a ternary complex with glucose and the Mg2 +-ATP before the reaction occurs. It makes a catalysis by proximity effect.
2^nd enzyme - Fosfohexose isomerase

This enzyme has an activity highly dependent on pH, suggesting a mechanism of action involving charged side chains of amino acids in its active center. In fact, the presence of a glutamate and a lysine in the active site of fosfohexose isomerase is essential for the catalytic activity of the same. This enzyme is highly steroespecific.

3^rd enzyme - Phosphofructokinase-1 (PFK-1)

The PFK-1 is the second regulatory enzyme of glycolysis, and is its main point of regulation. Presents a certain analogy with hexokinase, because the reaction is identical to that catalyzes the first reaction of glycolysis. At the structural level, it presents as a homotetramer.

There is another PFK, the PFK-2, which does not act directly in glycolysis, but is central to its regulation, because it controls the levels of fructose-2 ,6-bisphosphate, an important activator of PFK-1! (I will soon put a post on the regulation of glycolysis ...)

4^th enzyme - Aldolase

This enzyme is highly steroespecific. Presents three different isoforms (A, B and C), whose expression varies during the development of the organism. The major isoform in humans is the isoform A.

n glycolysis, the aldolase catalyzes a reaction known as retro-aldol condensation. There are two amino acid residues essential for the activity of the enzyme, a lysine and a cysteine.

5^th enzyme – Triose phosphate isomerase

The triose phosphate isomerase appears as a homodimer. Each subunit has a barrel-shaped structure, composed of eight alpha helices and eight parallel beta sheets. It was the first enzyme discovered to exhibit this type of barrel alpha / beta. This enzyme has a high dependence on catalytic function of pH, which indicates that performs an acid-base catalysis. In fact, there are three amino acid residues essential for its activity, a glutamate, a histidine and lysine. These amino acid residues play a role towards the establishment of hydrogen bonds that stabilize the transition state. Additionally, the enzyme has a loop with 10 amino acid residues highly conserved. This loop is important to stabilize the enediol (intermediate reaction) formed during the catalytic activity of the enzyme.

Triose phosphate isomerase is often mentioned as a case of "catalytic perfection", since it has a reaction rate controlled by diffusion. That is, the product formation takes place in a way as fast as the collision of the enzyme and substrate which limits the speed and is even spreading the product out of the active site of the enzyme.

Main bibliographic sources:

- Voet D, Voet JG, Biochemistry, Wiley

- Nelson DL, Cox MM, Lehninger - Principles of Biochemistry, WH Freeman Publishers