Wednesday 23 May 2012

Carbohydrate Metabolism


How The Aerobic Glycolysis Pathway Works:

In this article I will explain how the human Body intakes, breaks down, stores and utilizes energy in the Form of Carbohydrates. This process is vastly complicated and way beyond most humans capability to fully comprehend the complexity of the human body. I will be giving a general overview of all processes leaving out all the big names that will only cloud the vision I am trying to portray.
                First let’s start with the idea of nutrition. The human body is a complicated biological, electrical and mechanical machine and like any machine technology has created for our use, something has to power it. Most of the technology we use today is powered by electric power which is simply an electric charge that has formed around all atoms since the Big Bang. Understanding WHY there is electricity is a very crucial question, at least in my opinion, but with a very blatant response. It does not matter. The Electromagnetic Field discovered by Clark Maxwell, has been around since the beginning of our Universe. For the purposes of this article we will assume the Big Bang Theory is the correct theory. With this said I am sure in a few hundred years a brand new theory will completely wipe the slate of all we think we know and those seeming irrational religious church goers will point and laugh as the image of God seems more and more plausible. For now let us discuss the world how it is view currently because quite frankly it won’t matter what theories navigate civilization a few hundred years from now, well unless human life expectancy drastically spikes, which I doubt is too much of a concern.
                Back to Electricity. All particles in the universe are inside of a electromagnetic field. This gives particles a charge. Humans are made of particles and therefore can be said to run on electricity like a Lamborghini would.  All cells in the human body produce electricity, so why do we not simply plug ourselves into an outlet, charge up over night, unplug in the morning and then go on our merry way to our dreadful nine to five? Electricity it’s self does NOT power a cell. It will power a group of cells that make up our body. If cells no longer function then electricity no longer conducted throughout the body and inevitably we will die. So how do we keep our cells nice and happy? Just like humans needs sustenance to achieve a proper lifestyle, cells too need to be fed.
                What  feeds a cell though? Why can’t I simply inject a squashed Baconator into my skin and have the cells absorb it? Even though that would be an interesting idea the body has defenses to foreign particles and even burgers. Virology is a very complicated science that i will not pretend to understand the least bit of, but none the less the idea is simple. The body controls what goes in and out of the body just like customs at an airport. So if we can’t inject food then how do we feed the cells? We have to  go through the complex process of digestion. The concept of digestion is pretty simple and I want to quickly move onto the fun intra and extracellular processes so I will give the brief idea. Simply, food is chomped many times (hopefully) in the mouth, cut up into small pieces by front teeth and grinded by back teeth. Then the food goes into the esophagus which is one of the tubes leading down into the stomach. Peristalsis is the process of controlled contraction of the muscular rings circling the esophagus, like many rings stacked on each other. This pushes down the food into the stomach like pushing water out of a straw into a cup. Once there Pepsin, an enzyme, causes a further breakdown of the food into even smaller pieces.  Pepsin is the stomach acid often referred to that causes heart burn when accidently pushed into the esophagus and breaks down the epithelium. Epithelium is a fancy word for skin. There are many layers of these cells all with their own names that really do not matter at this point. After pepsin breaks down the bolus ( clumps of food) then it goes into the intestine. Here the nutrition is absorbed through the walls of the intestines until it is dried out, smelly and simply gross. Then the left over is excreted into a toilet, hopefully.
Now the fun stuff. Let’s start with sugars of the body also knows as carbohydrates. When a carbohydrate rich meal such as pasta is digested into the small intestine it is broken down into small parts known as glucose, fructose and galactose. Glucose is the major one used. Fructose is fruit sugar and in large amount can cause gastrointestinal distress. Galactose has to be converted into a substrate (building block) for Glycolysis and Gluconeogenesis, called D-glucose 6 phosphate. “D” determines the type of links formed in the molecule and determines what can be broken down by humans. We will talk about galactose later on when glycolysis and its reverse reaction, gluconeogenesis needs to be discussed. The sugars are small and can be directly absorbed into the blood stream from the small intestines and put into circulation throughout the body. Now we are ready to discuss our first process, Yippie.
Glycogenesis:
This is the process of storing a lot of glucose molecules in a compact state that can be then used at a later date. Most Carbohydrates are stored after digestion unless the individual is underfed or is in a state of high intensity exercise and needs the food immediately. Adenosine Triphosphate (ATP) the energy molecule of the body kicks off this series of reactions and the end product is a single molecule of glucose which  is added to a pre-existing chain of glycogen (many glucose molecules attached together). Uridine Diphosphate is the molecule that transports an attached glucose molecule to the glycogen chain. The idea of transporters is very crucial because many molecules cannot travel in the body unassisted by a carrier protein.  These are the “Diva’s” of the biological world. Now we have a large chain of glucose connected by 1,4 alpha glycosidic bonds.  To understand this let us look at the basic structure of a glucose molecule.



 Figure 1 a glucose molecule
 
Figure 2 -a part of a glycogen chain

There are 6 carbons in each glucose molecule and the bond that holds them together is known as a glycosidic bond. Alpha simply means that the bond is arranged in a way that humans can break it down. Beta bonds are present in other organisms such as plants. They have different enzymes that can break down these bonds that humans do not have. “1,4” simply means which carbon the bond is sprouting from.  Ie. the fourth and 6th carbon.
Pheew.  Hold on to your hats it gets more fun. Now we have created a nice bulk of glucose ready to use for the body. Let’s say the human we are using as a host for this article decides to get up and run at a moderately fast pace. Now the body has to use these glucose molecules to power the cell to create energy for the body. At a moderate intensity glucose is used due to the fact it is converted into energy the fastest compared to fats or proteins.  More on that later. So we need to make a molecule of glucose turn into energy for the body. ATP is the molecule we are trying to make which holds energy in its bonds. When the bonds are broken energy is released at it powers the cells. So how does a glucose turn into an ATP molecule? I’m glad you asked.
Glycolysis:
Many people remember this dreadful word in grade 10 science class and really do not want to revisit the horrid memories brought up at the thought of this word as it rekindles the emotional exhaustion of trying to remember the steps and names of the molecules and enzymes. Well, you’re welcome because I have taken this burden from you and am able to give you the take away messages. Generally what happens is that once molecule of glucose ( 6 carbons) is broken down into 2 three carbon molecules called pyruvate. This requires energy to create energy in very small amounts. Why you may ask. Glycolysis can be thought of as a preparation step where certain substrates are created in order to fuel two other steps that are crucial in creating ATP. It is a series of ten reactions that require enzymes at each to change the conformation of the molecules. At steps 1 and 3 ATP is used and the cell is at an ATP deficit.  But do not worry the molecule is broke into two smaller 3 carbon molecules and for each 3 carbon molecule 2 ATP are made at steps 7 and 10 so the net ATP production is 2 ATP At sep 8 2 molecules of NADH ( nicotinamide DInucleotide + a hydrogen molecule) are made which are used in the last step of this pathway. NAD is a carrier molecule along with FAD (flavinamide Dinucleotide) and carrier protons to the last part of the pathway. Do not worry we are getting there. So your net products are :
2 NADH
2 ATP
2 Pyruvates

Now we are ready to go into stage two of three of glucose breakdown. But let us not forget about the little step in between that requires Pyruvate to be transferred into another molecule that can be used in the next process.  Pyruvate combines with  coenzyme A and NAD, detaches a carbon and two hydrogen molecules and creates a molecule of acetyl CoA and carbondioxide along with a molecule of NADH.  Carbon Dioxide is broken down by other enzymes and reused in the body at different places where oxygen and carbon is needed. Acetyl basically means two carbon molecules. Unfortunately unless I want to write a 10, 000 word paper I cannot get into the language of biochemistry. All the words have a basic Latin root and basically tell you exactly what is happening. Ex. Lipolysis- the breakdown of fat. Lipo means fat, lysis means break down.  
Figure 3 Pyruvate Dehydrogenation process. Ie. Creating acetyl COA- it is more complicated then this but this is the main idea

The acetyl coA molecules each go into the Citric Acid Cycle also known as the Kreb Cycle.  This as well is a many step process with 9 steps all together. The kerb cycle goes around 2 times before dumping the products into the final step of the pathway. One turn of the cycle produces 3 NADH molecules, 1 FADH Molecule and 1 ATP molecule in the form of GTP ( Guinine Triphosphate) 2 molecules of carbon Dioxide are taken out of the cycle. With two turns of the cycle this brings the products to 6 NADH, 2 FADH and 2 ATP and 4 molecules of CO2 taken away.
Now we are up to a total of:
10 NADH ( 2 from glycolysis, 2 from intermediate step and 6 from CAC)
2 FADH ( from CAC)
4 ATP ( 2 from glycolysis and 2 from CAC)
***remember this is only from ONE glucose molecule and there are hundreds of these molecules. ***

Now for the Final Step of the process and possibly the most complicated. I will keep it simple though do not worry. The Electron Transport Chain is the last step and takes all the credit for the last 2.5 steps. Here the NADH’s and FADH’s transport their electrons to a series of 5 proteins known as complexes.  These are imbedded into the Inner Mitochondrial membrane and create an electron gradient. Some say this is a “proton gradient” but that is incorrect because protons are in the nucleus and if they were to travel out of the nucleus they would blow you up. Literally. Breaking apart nucleuses was how atom bombs were created. 
NADH goes to complex 1 and FADH goes to complex 2. Flavin Mononucleotide (FMN) takes H+ from the NADH and takes it to the complex 1. It is passed around like a hot potato to a few different proteins and complexes and finally goes to the ATP Synthetase. Non-Haem FE-S protein takes the electrons from FADH and does the same process but starting at complex 2 and these electrons also go to the ATP Synthetase.  Now the electrons are all out side of the inner membrane and due to diffusion the electrons want to come back into the cell to event out the particle balance in the mitochondria. The ATP Synthetase is a complex in itself and forces the electrons to help force a molecule of Adenosine Di phosphate and phosphate to fuse together to create ATP. It takes 4 electrons to create one ATP.




Figure 4- ETC- these are the complexes and the Hydrogens from NADH and FADH are stripped of electrons and passed liek a hot potato down the assembly line to the ATP Synthease.

So if we do some quick math we can determine the amount of ATP created per NADH. This turns out to produce 2.5 ATP per molecule of NADH and 1.5 ATP per molecule of NADH. Do not worry about the actual math it will not help you understand the body. Once the ATP is created then it can be used to fuel other processes in the mitochondria, which is of course the powerhouse of the cell.
If certain substrates are low the body can substitute certain ones for others, change some chemical structures and by pass some processes. Only to a certain amount of course but inevitably the processes never work perfectly and plan B and C and D need to be available. For example if low levels of CO Enzyme A , NAD then pyruvate can be  transferred into oxaloacetate which goes directly into CAC. Well, why not do this all the time and make life easier by taking out the pyruvate dehydrogenase reaction? By passing this step uses ATP instead of creating NADH which can be used in the ETC. Like I said. It can be done it times of need for energy but inevitably it will not last long.  This can happen with many different substrates and would take too long to list them all.

I will write an Article of Fat metabolism later. I hope you enjoyed. 


  ThanksJ

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