Published paper #2 Centrosome, centrioles and a tiny thing on centromere

If you have ever done anything on the cell before I’m sure you have heard of centrosome, centromere and centriole. Don’t get it twisted they are totally different things, and each time I hear of one my expression is always………

Though its not really my choice of vocabulary…….

But before we get into this review lets diferentiate.

Centiole: A centriole is a cylindrical shaped structure located near the nucleus of the cell and it function lies in the development of spindle fibres which play a major role during cell division. Specifially mitosis and cell division.

Centromere: A centromere is the point on a chromosome which holds two sister chromatides together, it is at this region where spidle fibres attatch and pull the genetic material towards the poles of the cell before cytokinesis occurs.

Centrosome:  Its main function is in the organisation of microtubules in animal cells. Which means that this structure is the reason why spidle fibres assort in a specific way for cell division. But not only does it regulate this assortment but it also plays key role in cell motility, signalling, protein trafficking/regulation(via the microtubule cytoskeleton) and signalling. I know that some of these sound similar to that of the centriole but I hope this diagram helps to clear things up.

How centrosomes perform their organizing structure:

MIcrotubules are structers formed by the polymerisation of “Tubulin”. And their active behaviour regulated by proteins. In the cell specific structures have these protiens and as such have the ability to independently control these microtubules. Within the cetrosome lies the cylindrical structures  centrioles  which are in turn surrounded by these proteins, referred to as pericentriolar material (PCM). Regulation proteins (NOT those referred to as PCM) by the centromere rely on the intrinsic polarity of the microtubules and motor proteins associated with them. Controlling the movement of these microtubules thus gives the centromere the ability to rgulate proteins and other substances across it, since it acts like a track along which they will pass. Regulation of this also gives speed of transport at variable quantities, based on the cells requirements.

Centrioles are unlike any other micreobubule assiociated organelle in the cell. It is composed of 0 triplets of stable microtubules aloocated in the well known cylindrical arrangement portrayed way at the very beginning. Centrioles can be mounted on the menbrane of a cell, at which point is it now referred to as”basal bodies” Thes basal bodies produce the stater material known as axoneme which gives rise to  the rigidity and mobility of cillia and flagella. within the centromere there are usually two types of centrioles.

• Mother centriole (older) : microtubules and distal appendages are docked here, i.e this is the point at which it is connected to the cell membrane
• Daughter centriole:

Microtubules produced by centriaoles are highly stable and are resistant to cold temperatue (which usually causes  microtubules to constrict) and are also resistant to alkiline pH changes

Petricentriolar Material:

Somewhere earlier I have mentioned that the PCM is involved in the controlling of microtubules. PCM determines the overall size of the centromere as well as its overall capability and efficiency and is composed of many different proteins, in humans being

• BBS4, Bardet-Biedl syndrome 4 protein
  
• Lck, Proto-oncogene tyrosine-protein kinase LCK
• PCM1, Pericentriolar material 1 protein
• TNKS, Tankyrase-1
• TNKS2, Tankyrase-2
• TUBE1, Tubulin epsilon chain

Importance:

It must be noted that centrosomes are not important in ALL organisms, for example somatic cells and Drosophila (common fruit fly) as well as man other animal cells (red blood cells etc) have no requirement for such a structure. However most animal cells do have a microtubule cytoskeleton.

• The microtubule cytoskeleton provides structural support and shape for the cell and allow for regulation of substances across it (these do not necessarily need to be formed via the centrosome)

Centrosomes are important in cell division and protein regulation and so if there is a malfunction in the centrosome or the centriole, a variety of issues can arise.

Abnormalities in the centriole duplication for instance is likely to be the origin of genome instability which is typically observed in cancer cells.  Centromere abnormality can occur from ear;y stages of human development and it is expected that if there is a fault in the centomere, there is a high probability that  fault would also occur in the PCM and the centioles themselves. Faults in either of these can cause

• Incomplete separation of cells during cytokinesis (can lead to a tumour)
• Incomplete separation of chromosomes
• improper regulation of proteins
• in terms of being a basal body can lead to abnormal development in cillia and flagella
• may totally disrupt reproduction of cells
• Roberts syndrome : a rare genetic disorder caused my the disruption of cell division

References:

http://www.ncbi.nlm.nih.gov/pubmed/22729084

http://www.biomedcentral.com/1741-7007/11/28

Published Paper 1

This is my first published paper review (its gonna need some updating)  and I have to admit, I had no idea of the complexity of enzymes and …my head hurts now so I shall not be going in depth to this article. Ofcourse you are free to read it on your own.

Have you ever heard of a Kinase Inhibitor Disease? I haven’t!

Firstly what is a kinase?

• A kinase is an enzyme which “modifies” a molecule by means of transfer of a phosphate from an ATP molecule to the molecule which takes part in the catalysed reaction.

According to the abstact of the article, Kinases have important roles when it comes to signalling pathways and cell regulation….. So what does this mean for humans, kinases….kinase inhibitirs….cell regulation?

I’m not sure what you are thinking but I do believe if you have a kinase inhibitor, you are basically not going to have proper metabolic mechanisms and therefore you are pretty much dying slowly 😦

Ok that may have been a little harsh.

The article goes on to mention that diseases (cancers, neurological and metabolic) often characterize the ability to deregulate kinase functions and it is expected that these may be a particular target when dealing with drugs. Meaning inhibitors are good…when using them AGAINST the diseases. However problems arise:

• They are large in numbers
• The lack selectivity/ specificity
• They tend to unintentionally interact with multiple protein kinases
• They are unbiased and so would react with the kinases which belong to the body (these are what cause side effects from drugs)

Yi-Yuan Chiu and associates have created a database on a mass number of kinases and inhibitors in order to find which would have been useful. This database is referred to as KIDFamMap.

KIdFamMap is the first database to explore the relationship between kinase-inhibitor-families (KIF’s) andKinase-inhibitor-disease (KID) with reference to the selectivity between enzyme and inhibitor.

SOME OUTSIDE INFO:

“A protein kinase inhibitor is one in which specifally blocks activity of one or more protein kinases.” Most of the kinases known today act on both serine and thysorine. I.e. they have a dual specificity. Kinases cause the phosphorylation of their complementary amino acids and since they can also react with histidine, a kinase may possess the ability to alter, interfere or even repair DNA. The fact that a kinase can affect DNA makes its inhibitor useful in the treatment of cancer.

Here is a list of drugs I found which target kinase inhibitors:

Name	Target	Company	Class	FDA Approval
Bevacizumab	VEGF	Genentech	Monoclonalantibody	2004 Colorectal
BIBW 2992	EGFR/Erb2	Boehringer Ingelheim	Small molecule	Not yet
Cetuximab	Erb1	Imclone/BMS	Monoclonal antibody	2006 Mar (SCCHN)
Imatinib	Bcr-Abl	Novartis	Small molecule	2001 (CML)
Trastuzumab	Erb2	Genentech/Roche	Monoclonal antibody	1998
Gefitinib	EGFR	AstraZeneca	Small molecule	2003
Ranibizumab	VEGF	Genentech	Monoclonal antibody	2006 (AMD)
Pegaptanib	VEGF	OSI/Pfizer	RNA Aptamer	2004 (AMD)

References:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531076/

http://www.news-medical.net/health/Kinase-Inhibitor-What-is-a-Kinase-Inhibitor.aspx

Collagen and Keratin

Well then, it’s been a while since I’ve been on this site. I don’t even remember what I have been doing half of the time *sigh*. Here is a little something about the basics of collagen and keratin. I get the feeling that I would be referring to it in the near future, not sure, but better prepared than not at all 🙂

Collagen

Collagen is a group of naturally occurring proteins, found in the bodies of animals. It is a triple helical structure, where two of its helical strands are fairly similar and the third has variation along random to specific points along its length, Like all other proteins is made up of a series of repeating amino acids but in the case of collagen, Proline, Glycine and its derivatives are in abundance.

In the human body, there are around 20 different types of collagen, they may be found in skin, hair and muscles, and thus it makes up about 25% of our body’s dry mass. As a matter of fact, collagen is in such abundance in our bodies that it is even the major constituent of cosmetic surgery.

So what makes collagen unique?

Arrangement of amino acids: Collagen contains some specific amino acids being Glycine, Proline,  Hydroxyproline and arginine, with the amino acid subunit, glycine making up about a third of the entire structure. This would mean that Gylcine repeats itself about every three amino acid units in the structure. One should know that glycine is the smallest and simplest amino acid possible, seeing that its R group is simply a hydrogen atom. So basically it’s TINY!

Since glycine is so small it is required in that particular position. Why? Because the assembly of collagen’s triple structure puts this residue on the interior part of the structure, since it is the only residue which would fit in such a compact position. What about the others? It’s simply because the R groups are too large that they would therefore have to point outwards.

Tensile Strength: The bonds which hold the residues of collagen together are covalent bonds, which are very strong molecular bonds. This covalent bond relates to the primary structure i.e. if an individual strand was to be straightened out. Forming the secondary structure are hydrogen bonds between residues of the helix. Now a single hydrogen bond is not strong in any way, but when a large number of them come together a relatively strong additive force is caused. 

Think of the strength like this. Ever broken a stick of macaroni? Simple right? Now try breaking five sticks at the same time. Still simple, but a little more effort is needed. Now try breaking an entire pack. It’s very difficult or maybe even impossible with average human strength. This is not the most accurate but a simple way to explain how hydrogen bonds work. Ant this high tensile strength is necessary. You have collagen in your bones and muscle tissue. Imagine if the collagen wasn’t this strong. Collagen is a major reason why bones are so strong, if it wasn’t for this quality your bones would be crushed under the sheer weight of your body, and thoracic and spinal organs/tissue would be under constant risk of injuries.

Types of Collagen

Keratin

Keratin is a fibrous structural protein found in animals and can be found in regions such as, hair, skin, nails, horns, hard part feathers etc.

Amino Acids and arrangement: Keratin’s arrangement is in the form of a poplypeptide chain (multiple amino acids linked together ) in the form of parallel sheets, the sheets which are held together by hydrogen bonds.
One of the amino acids present in keratin is Cystine, which makes up about ¼ of the entire structure. Cystine contains disulphide bonds, and it is these bonds which add to the stability of Keratin.

Tensile strength: Have u ever tried to burst a stand of hair? Ok, maybe when you have tried it simply slips between the small spaces in your hand. But assuming that it doesn’t trying to burst a strand of hair, takes a significant amount of effort , not exactly huge but, a little more than trying to burst thread.

Well Keratin AND Collagen is to blame for this. Earlier you have seen why collagen is so tough. Well the same basiacally applies to Keratin> Just remember that Keratin is NOT helical like collagen.

There is a video by Marshall Brain, where he takes a single strand of hair and sticks a number coins to it to see how much weight that single strand of hair can take before it finally snaps. (video refuses to upload so I’ll leave the link below)

I guess this is why Rapunzel’s hair makes her so…… I don’t know the word just look at it! It’s like, epic. 

References

How Strong is your Hair (by Marshall Brain)

http://marshallbrain.com/science/hair-strength.htm

Others

http://www.news-medical.net/health/Collagen-Medical-Uses.aspx

https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcRWExZM80_dwO5DRDRBEFDjXV0WwI1EZS8yVvcjmGedak3tTKWL

http://www.extremehealthradio.com/wp-content/uploads/2012/12/Collagen.jpg

https://encrypted-tbn1.gstatic.com/images?q=tbn:ANd9GcRwTUmuyBTzwee_zWJkq68O5ANflbkkoL5dcu3JpiecKr9nvpRY

http://3.bp.blogspot.com/-B0XIG6XnnA4/Tezl3KcWN6I/AAAAAAAAAGI/DOpfLcMdje0/s1600/amino-acid.png

http://www.pharmalot.com/wp-content/uploads/2012/10/pulling-hair-out.jpeg

http://0.tqn.com/d/movies/1/0/M/_/W/tangled-flynn-rider-rapunzel-photo.jpg

http://proteopedia.org/wiki/index.php/Collagen

http://web.sls.hw.ac.uk/teaching/Derek_J/A13MM1-web/Lectures/files/collagen/files/1_3.jpg

http://depts.washington.edu/bonebio/ASBMRed/matrix.html

http://www.livestrong.com/article/278235-collagen-deficiency/

http://www.columbia.edu/itc/hs/medical/sbpm_histology_old/slides/collagen.jpg

http://hmaloy.wikispaces.com/file/view/B-keratin.jpe/34211869/B-keratin.jpe

What is a protein?

FINALLY I have made a blog, hope your weekend was good btw.  I got a serious question for you guys

So, what IS a protein?

“any of numerous, highly varied organic molecules constituting a large portion of the mass of every life form and necessary 

in the diet of all animals and other non photosynthesizing organisms, composed of 20 or more amino 

acids linked in a genetically controlled linear sequence intoone or more long polypeptide chains, the final shape

 and other properties of each protein being determined by the side chains of the amino acids and their chemical 

attachments: proteins include such specialized forms as collagen for supportive tissue, hemoglobin for transport, 

antibodies for immune defense, and enzymes for metabolism.”

OK, well………………………………..

That is just a little TOO complicated. That’s the expression any non biochem student would have, so let’s break it down a little.

What is an Amino Acid?

Well, an amino acid is simply an organic molecule which possesses a carboxylic acid group and an amino group. AMINO Group + Carboxylic ACID= amino acid.

Well that made sense didn’t it? Let’s take it a little further. That amino and carboxyl group right there, they have the ability to form a bond with another amino acid since ALL would have the both groups. And when bonded they would look something like this.

All that is happening here is an O^– is coming off from the carboxyl group and 2 H⁺ from the amino group, which in turn come together to give a small molecule of water (Condensation Reaction). This bond between amino and carboxyl group is called a Peptide Bond. 

                So a protein is simply a large molecule made up of a series of amino acids bonded in this manner. Ofcouse there a many different proteins, all with their unique characteristics which would have been cause by the variation of their R groups.

Some Possible R groups are:

• Polar R groups (Positively or Negatively Charged)
• Non Polar R Groups (no Charges)
• Cyclic R Groups
• Basic R Groups
• Acidic R Groups

And there you go, just a simple explanation of what a protein, and amino acid are. Here is a little more in depth explanation of all of these PLUS a brief description of some of the types of amino acids.( http://www.youtube.com/watch?v=bcSz5zYdzbw )

SOURCES

http://dictionary.reference.com/browse/protein

http://www.youtube.com/watch?v=bcSz5zYdzbw&feature=youtu.be

PICTURES

http://www.whitetigernaturalmedicine.com/wp-content/uploads/2012/02/amino-acid-structure.jpg

http://img.sparknotes.com/figures/9/94eebfc3ef3ec1b04fe8b91e5bfa1f1f/fig5.gif

https://www.nationaldiagnostics.com/images/1_1_2b.gif

https://biochemnewb.files.wordpress.com/2013/02/20aminoacids.jpg?w=300