Friday, January 30, 2009

We can learn from cells about ... quality control

Do you know how rigid is “quality control” in cells? Extremely rigid, - especially in the making of our T lymphocytes. An estimated 99% of developing T cells do not mature, so only 1% survives and “sees the light of dawn”. Imagine that, only 1% survives the rigid development process! If that is not extremely rigid for you, then I don’t know what is.

T lymphocytes originate from the bone marrow but undergo development and maturation in the thymus. Here (in the thymus) they are well insulated from untimely and extraneous exposure to foreign substances as they undergo development and maturation. The developing lymphocytes are only exposed to foreign elements once it is certain that they can indeed recognize what is foreign and what is self. The thymus has extensive blood-thymus barrier that makes sure this proper environment is maintained.

A mature T cell (the "graduate" of “Thymus University”) must be able to do two important things:
a)recognize self from non-self (foreign) and
b)express receptors that can bind antigen plus self-MHC molecules*

If the T cell during its development untimely develops or does not develop those two attributes, then it undergoes apoptosis or cell suicide, (please see Nov 6 post, cells commit suicide).

So, many cells die on the road to development and maturation and only the elite 1% “graduate” from the “Thymus University”. Can you believe that?

This extremely rigid “weeding out” process is very important for the integrity of our own immune system. Imagine what will happen if the T cell “graduate” cannot recognize foreign from self? Then the T cells will attack our own cells (self)! This by the way is what happens when we suffer from auto immune disorder. What happened to the development of T cells here? This will be the subject of a future post.

So in essence, that is quality control in the cellular world. If the cell does not develop properly, then it is signalled to commit suicide. Only the best survives, no “pwede na” (that’s ok or half-baked) graduates (or end products) here. Is this rigidity at all possible in the human world? What do you think?

--------
*Major Histocompatibility Complex

Thursday, January 29, 2009

Why follow rules?

Following rules is very important in human society as well as in the cellular world. The difference is, cells follow rules “religiously” while humans tend to circumvent or even break or bend the rules. Maybe one of the reasons why we have problems in society is because we tend to do just that – either circumvent rules or break them.

I think we can learn a thing or two from cells. In the cellular world, everything flows smoothly. There is no chaos or anarchy. Why is this so? Well, because cells follow the rules or laws of nature.

For example, take a look at how cells generate energy...

When cells generate energy, they follow steps so there is no build up of both resources and products. There is always an enzyme that facilitates all processes every step of the way. Every process flows smoothly. No step is ever by-passed, there are no short cuts. The metabolic pathway that is followed is always the one that is the most energy efficient given the resources available. Every molecule in the cell "knows" its role and just awaits its turn to play its role. There is no jockeying for position because each molecule has its own time and place for action. There is no "me first, you later" in the cellular world.

Cells follow the rules of nature. We have the choice whether to follow rules of man or of nature. We have choice or freedom to choose, cells don’t have. So maybe there is really no parallelism. Cells “can’t help it” (but follow) but we can choose to follow or not. However, I strongly believe that if we just listen to our heart, we will also choose to follow the “laws of nature”.

In the cellular world, cells follow the laws of nature because these are programmed into their cellular “being”. I believe that in the human world we also have similar “laws of nature” programmed into our own being. However, we have problems knowing what these laws are because they are sometimes masked by the many distractions we have along the way. Many of us are beginning to sense however that indeed there are laws of nature that are also programmed in us. This is the reason why books like “A Purpose Driven Life” for example are so popular these days. We are now beginning to discover what our own “laws of nature” are.

Cells “know” their laws of nature and follow them “religiously” as I said earlier. We are just beginning to discover or rediscover our very own “laws of nature”. Once we do that and follow them, then I’m sure that our world will also flow as smoothly as that of the cellular world.

Wednesday, January 28, 2009

Why do cells put on "kinky" membranes when it's cold?


Remember, I mentioned in one of my earliest posts that cell membranes are my favourite part of the cell (Nov 1, my favourite part of the cell)? Today, I’d like to go back to cell membranes. Why? Well, the cold weather reminded me about what cells do to their membranes when their surroundings get cold.

As you probably know, cell membranes are basically made up of phospholipid bilayers. Then proteins are inserted into this phospholipid bilayer either half-way through or all the way through (please the diagrams above).

Most of the time, the phospholipid molecules in the membrane are fully saturated, so their “tails” appear straight as shown in diagram A. When the temperature gets cold however, the cells replace the saturated phospholipid molecules with unsaturated ones. The unsaturation or addition of double bonds in these molecules produce “kinks” in their “tails” (please see diagram B).

So what is the significance of these “kinks” in the phospholipid molecules? Well, because of the kinks, the molecules become harder to compress and therefore also harder to crystallize. Molecules have to be close together in order to crystallize them. If they are far apart, they cannot be crystallized. This process thus protects the cells because their membrane remains fluid and substances can still go in or out of cells. The same thing is impossible if the molecules are crystallized.

So when it’s cold, cells put on “kinky” membranes in order to survive. Isn’t that cool? (pun intentional)

Tuesday, January 27, 2009

Ghost cells, are they true?


Are there really ghost cells? Do they say “boo!”?

I know it’s a long way to Halloween but I thought that today would be as good as any other(day) to introduce a new cell, the “ghost cell”.

Well, “ghost cell” was originally used to describe a red blood cell that has lost its haemoglobin because of hemolysis. Since a human red blood cell has no nucleus, once it loses its haemoglobin, it appears like a “ghost” because only the cell membrane remains. So it appears just like a transparent circle, a ghost.

Lately however, the term “ghost cell” is also used to refer to any cell without any nucleus or cytoplasmic structures such that only the outline of the cell is visible.

One form of cancer, ameloblastoma, a cancer of the jaw and tooth related structures, is characterized by the presence of ghost cell tumor.

So ghost cells are really dead cells!Let's just hope they don't go a-haunting.

Monday, January 26, 2009

How did the chloroplast get its name?


source of image: http://gcse.wemew.org/data/Plant_cell.png

Years before the advent of powerful microscopes and other techniques for visualization of cells, simple microscopes only showed large cell organelles. One of the largest organelles is the chloroplast and microscopists simply used descriptive terms to explain what they saw.

Thus, chloroplast simply means “green particle” because that is how it appears under the microscope. In the same manner, leucoplast means “white particle” and vacuole is an "empty space or small cavity".

Saturday, January 24, 2009

CoQ, do we really need it?

Why is there so much hype about the importance of CoQ or CoenzymeQ (a.k.a. CoQ10, ubiquinone)? Do we really need it?

Well, CoQ is a naturally occurring substance that is found in our membranes especially the membranes of the ER (see Nov 21, 23), peroxisomes (see Nov 15), lysosomes (see Nov 19), and vesicles (see Jan 11). It is most abundant in the cristae of our mitochondria (see Jan 1-5) as it functions as one of the electron acceptors during energy production.

Because it can accept and transfer electrons, CoQ can therefore act as antioxidant too. Thus, it is usually recommended as a dietary supplement especially in adults and individuals with diminished energy-producing capacity.

There is thus a biological basis for all the hype about this substance. However, its role in preventing heart failure still has to undergo more tests.

Since CoQ is fat soluble, it is best taken during meals that contain oil and fat.

Friday, January 23, 2009

Why is it better to water plants in the morning?

Why is it better to water plants in the morning? Why, because water is needed by plants in the light-dependent phase of photosynthesis.

Plants and other photosynthetic organisms start the light-dependent phase of photosynthesis as soon as there is light. During this process, light energy trapped by chlorophyll splits water into an oxygen molecule and 4 protons. The oxygen diffuses out of the plants (and this is what we breath in) while the protons (or hydrogen ions) are used to generate energy molecules.

What happens then if we water our plants late in the afternoon? Well, I think you know the answer to that - this does not give the plants enough time to generate more energy as well as to release more oxygen.

The energy molecules generated here are used for the carbon fixation or the light-independent phase of photosynthesis.

By the way, since plants release oxygen during this process, this is another reason why we have to thank a green plant. Don’t you agree?

Thursday, January 22, 2009

Why should we thank a green plant?


Why, because plants do photosynthesis. Photo what? Photosynthesis, that’s what.

So what is this photosynthesis thing? Well, it is nature’s solution to the energy and carbon drain from our biosphere.

During photosynthesis, energy from the sun is transformed into chemical energy in the form of ATP and NADPH. Then this chemical energy is used to fix carbon atoms from carbon dioxide into large organic molecules like carbohydrates. These carbohydrates are then available to other organisms like us for our own energy needs.

We can see that light energy from the sun is needed in photosynthesis. The first stage (conversion of light energy to chemical energy) in photosynthesis is a light-dependent process. The second stage (fixing of carbon into carbohydrates) is light-independent so it can occur even in the absence of light. However, it still needs the products from the light-dependent process.

In order to make use of light energy, a family of green pigment molecules called chlorophyll serves as the trap for light energy. Thus, the only organisms that can make use of light energy are those that have chlorophyll, like the plants, some bacteria and some protists. Plants store chlorophyll in their chloroplasts.

Even if we stand under the sun all day, we will never be able to do photosynthesis and make our own energy molecules. All that we will be able to do is get sunburned. Why, because we do not have chlorophyll like the plants.

This is the reason why we sometimes see some posters that asks the question, “Have you thank a green plant today?”

Wednesday, January 21, 2009

saying hello without goodbye

Hello,
I was out for a week but was not able to say goodbye. Well, nobody seems to have noticed because I did not receive any inquiry. Anyway, I had to attend to some family matters in the province and didn't have a chance to say goodbye before I left.

I just want to tell you that I'm back. I will start my regular post tomorrow and pick up from where I left last time.

See you tomorrow.

Wednesday, January 14, 2009

Chloroplast


Source of image: http://www.helpsavetheclimate.com/chloroplast1.gif

Today, we will talk about the other energy generating organelle in cells, the chloroplast. We will also start with its structure and cover its function in future posts.

The chloroplast is much bigger than the mitochondrion. Just like the mitochondrion, it also has both an outer and an inner membrane that are separated by an intermembrane space. However, it still has a 3rd membrane which consists of flattened sacs called thylakoids. These thylakoids may be stacked together and form the grana (sing. granum) or may be unstacked and form the stroma thylakoids.

Chloroplast just like the mitochondrion also has its own DNA, mRNA, and ribosomes. These are located in the stroma.

Tuesday, January 13, 2009

marked for “death”

Do you know that cells mark certain proteins for “death”? I placed death in quotations because proteins are not alive, so they don’t die. Rather, they are degraded or broken into smaller units. However, “marked for death” is certainly a more catchy title than “marked for degradation”. Don’t you agree?

Anyway, our cells are constantly synthesizing proteins, exporting them, as well as degrading them. Since proteins form structures as well as act as enzymes and information molecules in cells, their amounts have to be constantly regulated. There should not be too much or too little of them inside the cell. Getting rid of excess proteins is thus a carefully controlled process.

The first step in the process is to mark the potential candidate for degradation. This is done by attaching ubiquitin molecules at several points in the protein where the lysine residues are found. Ubiquitination is the mark of “death”. Once marked, then large complexes of protein enzymes called proteasomes attack and break the protein into small pieces. Ubiquitin is thus the marker and proteasomes are the executioner in the “death” of a protein molecule. After the process, ubiquitin detaches and is recycled for future use.

So, if you are a protein molecule, beware of ubiquitin!

Monday, January 12, 2009

entropy and cells

Somebody asked me how I decide which topic to talk about in this daily blog. Actually, when I started this blog, I first focused on the main topics of Cell Biology. Thus, my first post (after the Intro) was about the basic requirements of cells and cell design. After that however, I would shift between cell design and the misconceptions that I usually encounter in textbooks or in students. Later, there is really no pattern in my posts. I would just talk about either the first topic that comes to mind or I would try to relate my post to the occasion as what I did last Christmas. Now, I talk about what ever inspires me for the day.

So what inspires me today? Yah, what? Well, I let my mind wonder through my “library” about cells and it paused on the concept of entropy. I know entropy is taken up more in physics, but entropy is also very much related to life. Why?

Well, the natural order of things (including living things) is towards entropy or towards increasing disorder. Yes, this is the natural order of things - towards disorder. If we notice, it is always easier to have disorder than order. It is always easier to break things than to make them because breaking order uses less energy than making order. 

Living things which are highly organized are not exempt from this natural tendency towards disorder or entropy. This order in our structure and function is what keeps us alive. If there is disorder in our structure and function, then we get sick or we even die. Therefore, living things including us must keep on doing something to prevent this disorder. So what is this something? This something is – generate energy and use this energy to prevent entropy.

Yes, this is the main reason why we must always generate energy. We have to maintain the order in all our cells. We have to maintain our structures, our high degree of organization, so we will be able to function. Thus energy production is a continuous process. We cannot stop generating energy. We need a constant source of energy therefore, so we can “bank against entropy” as how Lewis Thomas put it.

Sunday, January 11, 2009

Vesicles

Different kinds of vesicles abound in cells. They come in all sizes and content but they all transport something, be it towards the nucleus or towards the cell membrane or between cell organelles. Anyway, one thing is common among these vesicles; they usually have coats and markers. The coats generally indicate their source while the markers indicate their destination.

For example,3 types of coats are used by cells when they transport substances between the ER and Golgi: coatomer I (COP I), coatomer II (COP II) and clathrin.

Vesicles carrying newly formed proteins from the ER are coated with COP I while COP II coats vesicles that transfer substances between the different aspects of the Golgi apparatus. If a vesicle has to transport substances from the Golgi back to the ER however, COP II will coat this vesicle.

Usually if a vesicle contains newly finished product from the Golgi then clathrin is used to coat this. Newly synthesized lysosomal enzymes for example are clathrin-coated. Clathrin also coats newly formed endocytic vesicles. Actually these coats all help in the vesicle formation and later on in the transport process.

There are of course different markers for different destinations of these vesicles. So some vesicles are marked for lysosomes only or for “export”only.

Vesicle formation is actually a complex process involving many steps. What is presented here is a highly shortened version. And not all clathrin coats are the same.

Saturday, January 10, 2009

the cell's lab table

Do you know that cells have "lab tables"? Yes have. These are the ribosomes, the small non-membrane bound organelles composed of proteins and ribosomal RNA (rRNA).

Ribosomes consists of large and small subunits. The small subunit has a site for binding mRNA, a P-site for binding peptidyl tRNA and an A-site for binding aminoacyl tRNA. As you can see these sites are used during protein synthesis. Thus, ribosomes serve as the surface or the lab table for the synthesis of proteins.

By the way, the large and small subunits are manufactured separately in the nucleolus and also released separately to the cytoplasm. They remain as separate entities until the synthesis of proteins starts.

Friday, January 9, 2009

why water

It has been raining lately and this made me think of water. In my Nov 7, 2008 post (water world), I mentioned that water is the most abundant component of cells. In that post, I corrected a common misconception, that water is a universal solvent. It is not! It's just a very good solvent but it definitely is not a universal solvent!

In today's post, I will try to answer why water is the most abundant component of cells. Well, the reasons are because of its physical and chemical properties.

What are these properties? Among its important physical properties are: high specific heat, high heat of vaporization, high heat of fusion, high surface tension. Its dipole moment as well as its ability to form hydrogen bonds are its important chemical properties.

So what is so important about these physical and chemical properties? Well, because of its physical properties, water remains as liquid in a large range of temperature. It takes a lot of energy before water can be converted to vapor (high heat of vaporization) or solid (high heat of fusion). It can also absorb a lot of heat before its temperature changes even one degree centigrade (high specific heat). Thus, water does not easily get heated nor cold and this stability is very important for cells. If water is easily converted to vapor or to ice, can you imagine what would happen to our cells and to us if we find ourselves in very high during summer or very low temperatures during winter?

The high surface tension of water is also very important. This causes water molecules to create a film on surfaces and this is very important especially in maintaining breathing surfaces of our lungs.

The chemical properties of water are of course the reasons why water is a very good solvent. Their chemical properties allow them to  participate in many biological processes that keep us alive.

So there you are, those are the reasons why water is the most abundant component of cells.

Thursday, January 8, 2009

Counting ATPs

Students usually ask me how to count the number of ATPs formed during cell respiration. So I have prepared the following table that summarizes how and where ATPs are formed.

Before we go to that however, I just wish to point out that there are two ways by which ATP is formed. One is through substrate level phosphorylation and the other is through oxidative phosphorylation. During substrate level phosphorylation, 1 molecule of ATP is formed during each process. During oxidative phosphorylation however, 2 or 3 molecules of ATP are formed per process depending on the first hydrogen acceptor. If FAD is the first hydrogen acceptor, then 2 ATPs are formed while 3 ATPs are formed if NAD is the first hydrogen acceptor.

Another thing, we have to multiply by 2 all the ATPs formed because there are 2 molecules of pyruvic acid formed after glycolysis.

Reaction Type of Phosphorylation ATPs formed
Glucose to Pyruvic acid Substrate level 2 (net)*
Pyruvic acid to Acetyl CoA Oxidative 3 x 2
Krebs cycle and Ox-Phos Oxidative (NAD) 9 x 2
Krebs cycle and Ox-Phos Oxidative (FAD) 2 x 2
Krebs cycle Substrate level 1 x 2
G3P to 1,3DPGA in glycolysis* Oxidative via GP shuttle 2 x 2


* 4ATPs are actually formed. However, 2ATPs are used to prime glucose for the process.

**one step during glycolysis converts glyceraldehyde3phosphate(G3P) to 1,3diphosphoglycerate(1,3DPGA). This releases hydrogen ions and electrons that are accepted by NAD and brought to the mitochondrion through a glycero-phosphate shuttle (GP). So only 2 ATPs (instead of 3) are formed here (even if NAD is the acceptor) because 1 ATP is used to "pay" the GP shuttle.

Wednesday, January 7, 2009

of energy, equilibrium and imbalance

If you remember, I gave a quote (Dec 7 post) from Lewis Thomas about membranes. The last portion of that quote is: "To stay alive, you have to be able to hold out against equilibrium, maintain imbalance, bank against entropy, and you can only transact this business with membranes in our kind of world".

Today, I would like to focus on the line "... you have to be able to hold against equilibrium, maintain imbalance,..."

This line usually confuses students because they think that biological systems always try to maintain equilibrium and balance. So when I tell them the contrary, they get confused. How then do we remove this confusion?

Well, what I usually do is I ask them the questions: "What are the contents of cells?, What is the composition of the fluid surrounding cells?, What is the composition of earth?" Once they give the answers, they then realize that indeed cells have different composition from their immediate surrounding and from the earth. And the only way for cells to have a different composition from their surroundings is to "hold against equilibrium and maintain imbalance." This is of course only possible because of membranes and active transport. The membranes keep the substances inside cells and active transport maintains this difference in composition. And the only way cells can do this is by having a constant supply of energy.

Energy is thus needed to go against equilibrium and maintain imbalance. These make cells alive and different from the surroundings. Hooray for imbalance!

Tuesday, January 6, 2009

junk food and energy generation

Have you ever wondered why we call certain food as “junk food”? We usually understand that “junk food” has little or no nutritional value, right? Well, that is correct in a certain sense. However, there is another aspect to why “junk food” is junk, and this is related to what we have just covered in the last few posts about energy generation in cells.

One important process in energy generation is the maintenance of the proton gradient (see Jan 4 post). As mentioned: “This gradient drives the ions to move back to the matrix and as the ions pass through special channels that are associated with ATP synthase, ADP is phosphorylated to ATP.”

As you can see, the proton gradient is the one that drives the (hydrogen) ions to move back to the matrix and as they pass through special channels, energy (ATP) is created. If this gradient therefore is reduced or dissipated, then the driving force will no longer exist and no ATP is formed.

So what does this have to do with junk food? Well, here’s the connection. Some junk foods contain chemicals (usually the preservatives or coloring used) that reduce this proton gradient or driving force. How? These chemicals sequester or “smuggle” across the membrane the hydrogen ions without passing through the special channels with ATP synthase. Thus, no ATP is formed.

So, do you still wonder why “junk food” is junk?

Monday, January 5, 2009

energy generation in the mitochondrion, a summary


I have made this concept map to summarize all the processes of energy generation in the mitochondrion. I hope that you find it useful.

Sunday, January 4, 2009

Energy generation in the mitochondrion, part 3

This is a continuation of yesterday’s post. We are now in the final phase of energy generation, the oxidative phosphorylation. This process takes place along the cristae of the mitochondrion. This is the reason why I mentioned in one of the previous posts that the more folds or cristae there are, the larger the area for energy generation.

Oxidative phosphorylation is the only phase wherein oxygen is used. However, as mentioned before, preparation for this final phase actually starts during the formation of AcetylCoA from pyruvic acid.

The hydrogen ions and electrons that are generated during the Krebs’ cycle are transferred by the hydrogen acceptors to the different enzymes along the cristae of the mitochondrion. Here the electrons are transferred from one electron acceptor to another along the cristae while the ions are pumped across the cristae to the intermembrane space (see post on the structure of the mitochondrion). The ions thus create a proton gradient across the cristae. This gradient drives the ions to move back to the matrix and as the ions pass through special channels that are associated with ATP synthase, ADP is phosphorylated to ATP.

Oxygen acts as the final hydrogen acceptor as the electrons and ions rejoin each other and form water in the process.

Saturday, January 3, 2009

Energy generation in the mitochondrion, part 2


source of image: www.britannica.com
As mentioned in yesterday’s post, the next 2 phases of energy generation in cells are Krebs’ cycle and oxidative phosphorylation.

Krebs’ cycle is also known as citric acid cycle because the first substrate formed is citric acid. This process occurs in the matrix of the mitochondrion.

This cycle is an 8-step process that changes AcetylCoA to citric acid and the latter into oxaloacetate. Main products of this cycle are Hydrogen ions and electrons which are immediately received by Hydrogen acceptors and transferred to the last phase or oxidative phosphorylation. By-products of this cycle are CO2 and H2O.

Only 2 ATPs are actually produced in the Krebs’cycle itself. However, since it is coupled with the last phase, oxidative phosphorylation, 22 more ATPs are produced through the coupled reactions.

We will talk about the last phase of this energy generation in tomorrow’s post.

Friday, January 2, 2009

Energy generation and the mitochondrion

Energy generation or cell respiration consists of 4 phases: glycolysis, conversion of pyruvic acid to Acetyl Coenzyme A, Krebs’ cycle and oxidative phosphorylation.
The last 3 phases of energy generation take place inside the mitochondrion while the first phase takes place in the cytoplasm of a cell.

Glycolysis is an anaerobic process (does not need oxygen to proceed) that involves breaking down of a sugar molecule (usually glucose) into 2 molecules of pyruvic acid. If oxygen is still not available after this process, then pyruvic acid is converted into lactic acid in animal cells and into ethyl alcohol in plant cells.
If oxygen is available however, the 2nd phase of energy generation takes place, that is, pyruvic acid is converted to Acetyl Coenzymne A in preparation for the 3rd phase of the process.

Glycolysis yields 4 molecules of ATP (the energy currency of cells) but the net yield is only 2 molecules of ATP because 2 molecules are used up to prepare glucose for the process. On the other hand, phase 2 or the conversion of pyruvic acid to AcetylCoA yields a net of 6 ATP molecules.

The last 2 phases of cell respiration are coupled. That is, one cannot occur without the other. We will thus talk about these 2 in another post.

Thursday, January 1, 2009

Mitochondrion


source of image: www.britannica.com

I thought a good way to start the New Year right is to talk about cell energy and the mitochondrion.

The mitochondrion is an organelle that is involved in energy production. It is a rather complex organelle, it will probably take a few posts to completely its story.

Anyway, just to get started, let’s first talk about its structure today.

A mitochondrion (plural, mitochondria) is usually rod-shaped but this shape can change at anytime under varying conditions. It has a double membrane, the outer one being smooth and the inner one being thrown into folds called cristae (sing. crista). These folds increase the area for enzymes embedded in it and the more active a cell is, the more folds there are. Thus, a heart muscle cell for example has more cristae in its mitochondrion compared with a cartilage cell's mitochondrion.

There is a narrow space between the outer and inner membranes of the mitochondrion. This space is called the intermembrane space. Another space is found in the middle of the mitochondrion and this is called the matrix space or simply the matrix. Contents in both spaces differ.

The contents of the intermembrane space are somewhat similar to that of the cytosol whereas the matrix space contains many enzymes involved in the Kreb’s cycle process. Ribosomes as well as a circular DNA and tRNA are also found in the matrix.
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