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Published Paper Review 2- The ACCORD Lipid Trial

keep-calm-fight-type-2-diabetes

Type 2 diabetes, the most prevalent type of diabetes mellitus, is a disease that causes the body to inefficiently and inadequately utilize insulin. There is an increased risk of Atherosclerotic cardiovascular disease for older patients suffering from this ailment while other risks include obesity, hypertension and atherogenic dyslipidemia. These are the lipid defects that individuals possessing metabolic syndrome, insulin resistance and diabetes endures. Dyslipidemia is a consequent of elevated concentrations of plasma triglyceride (TG), low amounts of low density lipoproteins (LDL) and low levels of high density lipoprotein (HDL). Statins are inhibitors that lower the blood level of low density lipoproteins in non-diabetics and may also have the similar effect on patients with type 2 diabetes.  This treatment was not effective on the diabetic patients as the rate of atherosclerotic cardio vascular diseases remained high.

Statin drug

Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid trials, tested the proposition that fenofibrate treatment coupled with simvastatin therapy (to inhibit the synthesis of cholesterol), would be more plausible to reduce the risk of cardiovascular diseases in Type 2 diabetes than simvastatin therapy alone. It was hypothesized that treatment with fenofibrate would escalate the levels of HDL cholesterol by 5- 10%, having the least possible effect on the LDL concentrations while plasma TG Concentrations will be reduced by about 25%. It was stated by the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD), that the possibility of ailments such as myositis (inflammation of muscles) originating, would be negligible when fenofibrate combines with statin.

 Fenofibrate

    On other studies performed, Fenofibrate, although being a cholesterol reducer, did not reduce the levels of mortality attributed with coronary heart disease. The hypothesis was failed to be accepted for the lipid trial, because none of the outcomes from experimentation (for reduction) showed a statistically significant difference.  Correspondingly, in previously conducted trials, the fibrate treated groups showed an increased tendency for cardiovascular disease and mortality. Conversely, the sex of the test participants may have influenced the ascertained results, since the custom addition of the fenofibrate could possibly be more detrimental to women than men.

Lipid trial by the ACCORD proved to be a failure in aiding the reduction of cardio vascular illnesses and Type 2 Diabetes. Nonetheless, it has opened a new avenue for treatment among patients and may lead to new discoveries to cure diseases in humans such as treating high cholesterol. I am intrigued by this step forward in the treatment of diabetes as I feel assured that individuals are working hard to combat these lifestyle diseases that cause hardships, inhibiting an enjoyable life for all those affected. It is evident that the scientists are learning from their failures to tackle this monster disease. It build my pride as a biochemistry student!

This would be the last Published paper review on behalf of the Biochemistry3rst team; make sure to look out for our final reflection done by me, being uploaded this Sunday!

Shiv Shiv out!

 Bob has Diabetes 2

Reference:

Ginsberg, Henry. 2011. “The Accord (Action to Control Cardiovascular Risk in Diabetes) Lipid   Trial.” Diabetes Care. Volume 34, Supplement 2.                               http://care.diabetesjournals.org/content/34/Supplement_2/S107.full

Picture References:

Keep calm and fight Type 2 Diabetes- http://sd.keepcalm-o-matic.co.uk/i/keep-calm-and-fight-type-2-diabetes.png.

Statin Drug- http://foodandhealth.com/blog/wp-content/uploads/2013/11/Screen-Shot-2013-11-19-at-11.28.15-AM-300×267.png

Fenofibrate- http://www.tajpharma.com/products/Generics/Fenofibrate/Fenofibrate-200mg-10-capsules.jpg

Bob has Diabetes- http://home.comcast.net/~testytester/diabetes.jpg

REFLECTION 9- LOVELY LIPIDS PART 2

 

Butter

Hey there folks!! Rakeeru here and it’s finally my turn again to share some thoughts on this blog. This week was pretty much wacky because there was so much to do and so little time to do it. I kid, I kid! I ‘m a master procrastinator but nothing can stop me from sharing some cool stuff about lipids. My love for lipids will never die… lol. My mission is to help you understand lipids in a fun and enjoyable way. So we are going to be looking at three types of structural membranes of lipids, phosphodiate, Sphingosine and cholesterol.

Procrastination

Let’s talk GLYCEROLPHOSPHOLIPIDS! So you guys should be familiar with the structure of glycerol, but if you aren’t, then let’s recap a bit. Glycerol is an alcohol that has three carbon atoms, each bonded to an alcohol group.  Okay let’s go back to the glycerol phospholipids now. A Glycerol phospholipid, also known as a phosphodiate, has a glycerol as his backbone, where on carbon 1 only a saturated fatty acid chain is attached. On carbon 2 an unsaturated fatty acid chain is bonded and last but not least on carbon 3 a phosphate group is directly bonded to it. Note that when an alcohol is attached to an acid group it forms an ester bond.  Look at the lovely diagram below.

Glycerolphospholipid

A Glycerolphospholipid!

Now this entire molecule is said to be amphipathic, meaning it has a polar end and a non-polar end. (See picture below). The polar end is hydrophilic or “water loving” while the non-polar end is hydrophobic or “water hating”. The polar end is the made up of a phosphate group and a hydroxyl group.

Apolar, Polar

An amphipathic compund

(R1 and R2 represent the fatty acid chain , the X represents the hydroxyl group) So Trav told you about the ability of unsaturated fatty acids to form a kink, and I just want to add a few things to that… Not all unsaturated fatty acids show a kink (changes direction of the chain). Unsaturated fatty acids can either be in cis configuration or trans configuration.  ONLY CIS fatty acid chains display that appearance due to the fact that the C-3 and C-6 are on the same side of the double bond. (see the diagram below). In a trans fatty acid chain, the structure does not show any kinks. Instead, it follows the pattern of the fatty acid. It resembles the saturated fatty acid so  I call it “the sly one”, since I cannot tell which one is the unsaturated fat and which in the saturated. O Boy, knowing that all the good-tasting stuff (junk food) is high in trans-fat which is terrible for health is a little scary, since the transfatty acid is packed tightly which increases the LDL( Low Density lipoprotein) and decreases HDL (High Density lipoprotein).

cis, tran fatty acids

Showing off the kink

Okay moving on.. moving on… Another amazing lipid is… SPHINGOLIPID!!!  😀  This structure has a sphingosine backbone; sphingosine is an alcohol that has 18 CARBONS. There are many different functional groups attached to it. On carbon 1 and 3 there are hydroxyl groups present, an amino group attached to carbon 2 and a trans double bond is present in the middle of carbon 4 and 5. (See drawing below)

Sphingosine

  Remember I mentioned sphingosine is the backbone of the sphingolipid. What makes it a sphingolipid? It’s the presence of a saturated fatty acid chain. This fatty acid attaches to the carbon 2 that is bonded to an amino group to form an amide bond.

Sphingosine and Fatty Acid

A Sphingolipid!

On carbon 1, there is an R group; this is simply any other group that is attached to the carbon, for example if hydrogen is R group then the name of the entire structure is ceramide.  Ceramide is an oily substance that is found on the outer layer of the skin. It basically adds moisture to skin, which helps to prevent skin from drying and flaking. (Curel, 2014).  Another example is sphingo myelin, which is created when the R group is phospocholine. The sphingo myelin is found in red blood cells and myelin sheaths. What captured my attention is that sphingo myelin increases the speed at which nervous impulses conduct themselves by insulating the nerve fibers. (Voet, Voet and Pratt, 2008). Pretty kool stuff. 😀 Last but not the least, Cholesterol!!!  I’m sure you heard of this word before. But what exactly is cholesterol?  Well here goes, cholesterol is a molecule that has 27 carbons. This molecule has 3 rings that have 6 carbon atoms and 1 ring that only has 5. These rings are referred to as steroids and are stuck together.  Looking at ring B there is a double bond between carbon 5 and 6. There is a hydroxyl group on the carbon 3 atom and there is an alkyl group on the carbon 17. There are 2 methyl groups, one on carbon 19 and the other on carbon 18. By the way, in case you forgot what an alkyl group is, it’s a fragment of a molecule that has a general formula (CnH2n+1,). (Senese, 2010).

 Cholesterol

  Well what’s so important about cholesterol?  Believe it or not, without cholesterol we wouldn’t even exist. You know what’s amazing? The body is able to produce cholesterol on its own without consumption of food rich in cholesterol. (Mason W. Freeman, 2014). It plays an important role in the body:

  • it forms bile acids to make digestion a lot easier in the intestine,
  • Having cholesterol allows the body to produce vitamin D or hormones like testosterone. Testosterone is a steroid hormone that is produced in large amounts in males. It is responsible for the defining characteristics in men, and also for overall health and wellbeing.
  • Cholesterol, together with phospholipids, makes up the membrane of cells in animals.  Each cholesterol molecule attaches itself to a phospholipid group. The hydrophilic end of the cholesterol (where the hydroxyl group is located) is close to the hydrophilic end of the phospholipid. The hydrophobic portion of the cholesterol interacts with the hydrophobic portion of the phospholipid.

Just to spice things up a bit, have you ever wondered how cholesterol affects the fluidity of the membrane? Well it all depends on the temperature. In high temperature the cholesterol controls the movement of the phospholipid and lessens the fluidity. Heat energy encourages the phospholipids to move a lot which will destabilize the membrane. In low temperature the cholesterol controls the phospholipid by avoiding compaction. In cold conditions the phospholipid moves less and will become rigid.

Fluidity of membrane

Well that’s it for now! I hope my reflection was very informative and you guys learnt from this… Biochemistry is fun! BEST OF LUCK IN YOUR STUDIES!!!   😦 Unfortunately this is my last reflection… but my best buddy Shiv Shiv will do a tremendous job! Next up is nucleotides.. soo stay tuned… Until next time Rakeeru out!

Lipids can be good

 

 References:

 

Picture References:

 

Youtube Video Review 2- ATP & Respiration – Hank Green

Hey everyone, Richie here! As I was browsing about the Internet, I came across this interesting video on respiration, and I thought I would share my thoughts on it. 🙂 The topic being discussed is cellular respiration, which is essentially the process by which organisms obtain energy from their diet. The glucose gained from the food we eat combines with oxygen to form carbon dioxide, water and energy. This energy now needs to be converted to ATP so that the body can use it. Now, there are three steps in converting glucose to the desired product of ATP, which are glycolysis, the Krebs cycle, and the electron transport chain (ETC). In glycolysis, glucose, a 6-carbon compound, is eventually broken down to two 3-carbon compounds called pyruvate molecules. Two ATP molecules are invested into this step so that a net gain of two ATP can be made, as well as two pyruvates and two NADH. This process occurs without the presence of oxygen in the cytoplasm of cells. The Krebs cycle, named after Hans Krebs, occurs in the inner membrane of the mitochondria. The two pyruvates made in glycolysis are used up to form Acetyl CoA, which combines with oxaloacetic acid to produce citric acid. A series of oxidation reactions occur for citric acid to be converted to oxaloacetic acid, and the cycle is repeated to use up both pyruvate molecules. The last step is the ETC, where the electron carriers NADH and FADH2 use the electrons that they are carrying to provide energy for the movement of protons across the inner membrane of mitochondria. At the end of the three steps, it takes one glucose molecule to generate about 38 molecules of ATP.

The cell respiration process!!! All in one Diagram!

The cell respiration process!!! All in one Diagram!

After listening to this video, I can say that I definitely understood the points that the presenter had made. He was able to take complicated processes, such as glycolysis and the Krebs cycle, and break them down into simplistic concepts which were easy to grasp. It was also interesting how the presenter didn’t just dive straight into the topic, but instead, he chose to show the viewers the relevance of ATP production in the body by using the example of exercise. However, the level of detail that we are required to know on this topic was not covered in this video. He gave a brief overview of the processes that go on in cellular metabolism, but did not go into much detail about the actual steps of each process. An improvement that can be made to this video is to go through the technical aspects of this topic in a little more detail to ensure that the viewers appreciate all the steps of cellular respiration. Therefore, I think that this is a good video to help persons to understand the basic concepts entailed in cellular respiration, but not a good video to study from.

So guys, it’s been a pleasure science-blogging you guys… this is it for me… it has been a really fun and edifying experience, personally! I speak for myself but my amazing colleagues will be singing the same tune when their turn arrives, I hope you follow our blog and attempt our activities (even check out and ‘thumb’s up’ the video we made on enzymes lol) my bones still aching… just kidding lol take a look at the video and you will see why :).

Rock star Richie OVER AND OUT!!!

http://www.youtube.com/watch?v=00jbG_cfGuQ

Picture Reference:

Cell Respiration Process – http://upload.wikimedia.org/wikipedia/commons/7/74/CellRespiration.svg

Reflection 8 –Lipids 1

Hey y’all! This is your boi Trav here again bringing to you yet another reflection! This one being on… drum roll please… Lipids! Yes Lipids! How fortunate am I to do another topic that interest me due to my current lifestyle… you know with the gym and all… Well what can I say about lipids… when I think of lipids and I think about Fats… when I think about fat, I think about losing it! Lol. Yes, yes I know fats aren’t all bad. So! I’m sure you guys are dying to know what lipids are, so let me get started. 🙂

So-your-saying-

Okay, so Lipids are made up of long chains of carboxylic acids that are the building blocks of most lipids. It is made up of a wide range of different classes. These common classes of lipids include: Fatty Acids, Triacylglycerol, Phospholipid, Glycerol, and Steroid. For this reflection, you would be seeing three words a lot. They are: Fats, Oils and Lipids. Lipids are used to refer to both fats and oils, Fats are used to refer to the solid form of lipids and well you can guess what oils are used to refer to. Yes, it’s when we talk about the liquid form!!! Fats are solids because they are made up of carbon chains saturated with hydrogen atoms, while oils contains unsaturated hydrocarbon chains. Oils can have at least one carbon-carbon double bond that disrupts complete saturation and if there are more than one, it is termed polyunsaturated. Oh, I should emphasize that since fats are saturated hydrocarbons, they do not have any carbon-carbon double bonds. There is also a substance known as Wax which is made up of a Fatty acid and an alcohol (long chain). Waxes are important in fruits for protection and also appearance. Fatty acids comes in different chain lengths: Short (less than 6 carbons), Medium (6-12 carbons) and Long (more than 14 carbons).

Fatty acids, triglyceride, steroids etc

Fatty acids have some rather important functions for organisms that include:

  • Insulation from the cold (bears during hibernation),
  • Energy source/storage,
  • Helps cushion and protect your vital organs such as your kidneys, liver and heart.

Fat will give you more energy per gram than carbohydrates since it is in a more reduced form. This reduced form indicates that there is a lot less oxygen than a carbohydrate which means a lot more oxidation would take place. More oxidation means more energy. They supply Essential Fatty Acids such as Linoleic and linolenic acids. Fatty acids also help form the cell membrane of cells due to the phospholipids bilayer.

Saturated Fats are all bonded to Hydrogen and as stated before there are no C-C double bonds. They have long, straight chains and it is solid at room temperature. Unsaturated fats are those with the presence of the carbon-carbon double bonds. Unsaturated fats are liquid at room temperature because in the cis form, kinks where double bonds are found, prevents molecules from being tightly packed hence they are in the liquid form.

So what is the structure of Fatty acids?  Fatty acids are made up of 2 different ends, the methyl and carboxyl end and many Hydrocarbon bonds (CH2) in between the 2 ends. A wonderful diagram is provided for you below :).

 

methyl and carboxyl ends

Diagram showing the methyl and carboxyl ends with Hydrocarbons inbetween

What caught my interest is the patterns found in fatty acids. One being that there is an even number of carbon atoms. The other is the location of the double bondsfor most monosaturated fatty acids (1 double bond), the double bond is found between carbons 9 and 10 while for polyunsaturated fatty acids, it is usually found at carbons 12 and 15.

Now I shall talk about the characteristics and trends that occur in fatty acids. As the number of Carbons in the Fatty Acid Chain increases, the Melting point increases. Also when the number of carbons increases, the Solubility in water decreases. An interesting point to note is that the melting point varies for saturated fatty acids and for unsaturated fatty acids. For example, between Stearic acid and Linoleic acid… Stearic Acid is a saturated fatty acid which means there are no double bonds. These are solid and also are tightly packed molecules. Linoleic acid is an unsaturated fatty acid and contains 2 double bonds. If you remember from what I mentioned above, unsaturated fatty acids are liquid at room temperature and they are not tightly packed. These characteristics proves that Linoleic Acid has a lower melting point than Stearic acid, having a melting point of -5°C and stearic acid having a melting point of 69.6°C. Oh! Something to note… as the number of double bonds increases the melting points decreases.

melting point of lipids

Lipids also have a physiological function: It is said that the chain length and amount of fatty acids is important for the fluidity of the membrane. It needs to be regulated in order to maintain this fluidity of the membrane lipids. Unsaturated Fatty acids especially are important as it promotes the fluidity. This is due to the unsaturated fats’ kink which creates something called the “ elbow room” that forms a space in between fatty acids giving enough room to ensure that the membrane is not too rigid.( Cnx Biology, 2013.)

fluidity

Essential Fatty Acids are those Fatty Acids that cannot be made by the human body. So how is it that we acquire these essential fatty acids? Well just like for amino acids, they are gained by the food that we consume and digest. Good examples of Essential Fatty acids are the omega-6 linoleic acid and omega-3 alpha-linolenic acid. They are rather important for human health. I will discuss the benefits of these a little later, so something to look forward to! So what do you think Non-essential Fatty acids are and where do you think we attain these? Well I am sure you guessed that these are produced by the body and therefore not needed in our diet. Oh and like I stated for amino acids, essential and non-essential substances are both important, not just the essential fatty acids. Lol Déjà vu moment…

Essential fatty acids

Now something a little different, what we are gonna talk about is what happens when we add hydrogen to an unsaturated fatty acid. What happens is, first the carbon-carbon double bond is broken. This leaves room for the carbon to bond to another hydrogen. This produces only single bonds and this process is known as Hydrogenation. Better manipulation and shelf life increases for the food industry by this process. This process also produce the “bad” fats known as Trans Fats and they are found in most fried foods as well as margarines. Trans fat is created when hydrogen is added which makes the oil last longer. The problem with it is that it increases your Low-density Lipoprotein (LDL) Cholesterol and decreases your High-density Lipoprotein (HDL) Cholesterol. LDL Cholesterol leads to a build-up in the artery which can lead to atherosclerosis. This means that it increases one’s risk of getting a heart attack. Yikes! That’s not good! 😦

atherosclerosis-

That was a little scary so now something to make the mood lighter! So, have you guys wondered how you can measure and test whether a substance is saturated or not and if it is unsaturated to what degree? Umm I will go ahead and assume no… lol. Okay… so yep, there is a way by introducing iodine and measuring the amount of iodine that can react with the unsaturated fatty acid. This is called the Iodine Index. The higher the percentage of unsaturated fats found in the food/ substance, the higher the Iodine index will be. It is similar to hydrogenation as it breaks the double bond and bonds to the molecule. Oh and it is important to note that 1 mole of Iodine reacts with the compound.

iodine index of lipids

Glycerol! Yay! Time to talk about it lol. These guys got three hydroxyl groups and three carbons attached to them! What is special about glycerol is that they can combine with three fatty acids on the hydroxyl group. This is possible because the hydroxyl group on the glycerol combines with a carboxyl group of the fatty acid. This undergoes a condensation reaction where a water molecule is lost and the bond formed is known as an ester bond. The compound that is produced from this reaction is known as a Triacylglycerol or TAG molecule. One thing to note is that the TAG can also be hydrolysed using an enzyme known as lipase to break it down back into the Glycerol and the three fatty acids. It is also possible to break down a triglyceride using a strong base to convert it into a soap and a glycerol molecule.

triacylglycerol

Well that’s it for Lipids! Don’t go yet though! Just as I stated earlier, I got some information on the benefits of omega-6 linoleic acid and omega-3 alpha-linolenic acid to share with you!  These two acids are Polyunsaturated Fatty acids (PUFA). They are also essential fatty acids as they cannot be produced by the body and are therefore acquired from your diet. For omega-3, food sources include: Canola oil, Flax seeds, Seafood, Pumpkin seeds, Eggs and many more… For omega-6 sources include: Soybean oil, corn oil, sunflower oil, canola oil and eggs again. I know you guys must be fed up of reading so I will put the benefits of these acids in point form.

  • Helps lower the “bad” LDL cholesterol which ensures the decrease in cardio vascular disease potential.
  • Helps reduce inflammation which prevents many different types of illnesses
  • Helps with growth and development
  • Important for brain development

 Linoleic and Linolenic acid

Okay… it seems I am all out of juice… no more information for me to share with you… sniff sniff :(… wish I could have continued the rest of Lipids but that’s the job for our next reflector… my good friend Rakeeru! So see you guys around… Hope this wasn’t too tedious and long to read. Hope you guys learnt something new from all this. So! Until next time Trav out!

Out of Juice

 References:

http://cnx.org/content/m44416/latest/#fig-ch05_01_03

http://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/trans-fat/art-20046114

http://www.webmd.com/cholesterol-management/ldl-cholesterol-the-bad-cholesterol

Picture References:

Reflection 7- TCA and ETC…… what are these strange abbreviations o_O

Hello again my Biochemistry enthusiasts! 🙂 This is Reshi here, and boy has it been a stressful semester so far. To add to the stress, I wasn’t sure what I was supposed to write for this topic of TCA and ETC. Well, I remember the ETC part from high school, but when I saw TCA, I got a mental block. I don’t remember ever hearing about that cycle! I probably must have fallen asleep in my Biology class again. So on doing some research, I saw that the TCA cycle is the same thing as the citric acid cycle, or the Krebs cycle. Now that I remember lol.

Cellular respiration process!

Cellular respiration process!

Since we are on topic of the TCA (tricarboxylic acid) cycle, or Krebs cycle as I remember it, I would like to share a few thoughts on it, as well as on the ETC (electron transport chain). So we are all familiar with the fact that cellular respiration is essential for us to produce energy. The site of energy formation is the mitochondria and thus, these structures are plentiful in our body cells. As Richie had discussed in last week’s post, glycolysis is the first step in this energy formation process. The whole point of glycolysis, well at least in my opinion, is to produce two molecules of pyruvate, as well as two molecules each of adenosine triphosphate (ATP) and NADH. A link reaction then occurs in the mitochondrial matrix, which links the glycolysis and Krebs cycle together. Here, the pyruvate molecules become oxidized to form Acetyl CoA. 2 pyruvate + CoA + 2NAD+ —> 2 Acetyl CoA + 2CO2 + 2NADH

The Link Reaction in action!

The Link Reaction in action!

Now this is where my part comes in. The formation of the product Acetyl CoA is a vital step because it is used in the initial step of the TCA cycle. Before I go further, it is important to note that while glycolysis occurs in the cytoplasm of cells, the TCA cycle takes place in the matrix of mitochondria. This is where things can get pretty technical, so just bear with me as I try to simplify this process. So we have our two molecules of Acetyl CoA that have been formed essentially from one glucose molecule. However, only one of these 2-carbon structures can undergo the TCA cycle at a time, and thus, the cycle must be repeated so that both Acetyl CoA molecules are utilized.

The TCA/ Krebs Cycle

The TCA/ Krebs Cycle

  • At the beginning of the cycle, Acetyl CoA interacts with a 4-carbon structure known as oxaloacetate to form citrate, which is a 6-carbon compound. This reaction is catalyzed by citrate synthase. It is important that side reactions be kept to a minimum, since this initial step is very crucial to the entire cycle.
  • Since the position of one of the hydroxyl groups on the citrate molecule is not conducive to the process of oxidative decarboxylation (an oxidation reaction whereby a Carbon atom is lost), the structure needs to be slightly rearranged (Berg, Stryer, and Tymoczko 2002). Hence, the isomerization of citrate to isocitrate occurs. Isocitrate is also a 6-carbon molecule.
  • The next step is the conversion of isocitrate to α-ketoglutarate. We are moving from a 6-carbon to a 5-carbon structure, which indicates that oxidative decarboxylation is taking place. This redox reaction is catalyzed by isocitrate dehydrogenase. NAD+, an electron carrier, becomes reduced to NADH by utilizing the energy released from converting isocitrate to α-ketoglutarate.
  • Another oxidative decarboxylation reaction occurs in order for α-ketoglutarate to be converted to succinyl CoA, which is a 4-carbon molecule. Again, NAD+ is reduced to NADH and H+.
  • Succinyl CoA then goes on to form succinate, and is catalyzed by succinyl CoA synthetase. Guanosine Diphosphate (GDP) uses the energy given off from this reaction to combine with an inorganic phosphate and forms Guanosine Triphosphate (GTP). In the presence of nucleoside diphosphate kinase, GTP can be easily converted to ATP.  (GDP—>GTP—>ATP) 🙂
  • The last set of reactions is the conversion of succinate to the product oxaloacetate. However, this conversion has a few steps in between. Firstly, the succinate undergoes an oxidation reaction catalyzed by succinate dehydrogenase to produce fumarate. Another electron carrier, FAD, is involved in this particular reaction instead of NAD. This is because FAD is capable of removing two hydrogen atoms from a given molecule.  The FAD undergoes a reduction reaction to form FADH2. Then, a hydrolysis reaction occurs in the presence of fumarase catalyst, whereby fumarate is converted to malate. Lastly, malate undergoes oxidation with the catalyst malate dehydrogenase to form oxaloacetate. This time, NAD is used as the electron carrier and becomes reduced to NADH+ and H+.

So basically, after that long, complicated process, the whole point of the Krebs cycle is to generate reduced NAD and Reduced FAD so that they can be used in the next step of cellular respiration, which is the Electron Transport Chain (ETC).   In the ETC, a series of redox reactions occur as the electrons pass along the electron carriers. These carriers (large protein complexes) release energy, and this energy is used to make ATP. This process can be summed up in the Chemiosmostic Theory. I think I should expand a little more on this very interesting hypothesis.

The reduced NAD molecules go into the ETC and loses their Hydrogen. Each Hydrogen atom that has been given up splits into its constituent protons and electrons.

H —>H+ + e

The Electron Transport Chain!

The Electron Transport Chain!

The protons that arise from the split Hydrogen atoms are pumped into the intermembranal space in the mitochondria to increase the proton concentration. Since there is a high concentration of positive protons in the intermembranal space, these protons will move from a higher concentration to a lower concentration in the mitochondrial matrix down its electrochemical gradient. As protons leak from the intermembranal space through special protein complexes back into the matrix, the energy dissipated is used by ATP synthase to convert one ADP (adenosine diphosphate) to one ATP (adenosine triphosphate) for each pair of protons. Thus, each reduced NAD pumped three pairs of protons to produce three ATP molecules. Likewise, each reduced FAD pumps two pairs of proton which produces two ATP. At the end of the ETC, the electrons combine with a Hydrogen ion and an Oxygen atom to form water.

½ O2 + 2H+ + 2e —>H2O

The formation of water results from the electron carrier cytochrome c which contains the large transmembranal protein, cytochrome oxidase, to catalyze the above reaction while facilitating the pumping of protons from the matrix into the intermembranal space via energy released from the electron produced from the first equation. Okay, I know that was a lot of information to take in, but take it one step at a time. Just remember that respiration is not simply the intake and exhalation of air, but a series of biochemical reactions that result in the formation of energy. Sadly this is my last reflection 😦 and I must say, I really enjoyed doing these posts! So until we meet again in the future, this is Reshi closing off. Keep calm and study hard my Biocheminions!!!! 🙂

 

References:

http://www.ncbi.nlm.nih.gov/books/NBK22427/ http://chemistry.about.com/od/biochemistry/ss/citricacidcycle.html

 

Picture References:

Link reaction and Krebs- http://img.docstoccdn.com/thumb/orig/44745072.png.

Cellular respiration- http://www.uic.edu/classes/bios/bios100/lectures/09_08_cellular_respiratio-L.jpg

Link reaction- http://revisionworld.co.uk/files/LinkReaction.JPG.

Krebs Cycle- http://13morima.files.wordpress.com/2011/11/krebs_cycle.jpeg

ETC- http://cnx.org/content/m46451/latest/2508_The_Electron_Transport_Chain.jpg

MCQ Structured Question on Glycolysis!

                   Which of the following is true about glycolysis?

 I.            Glycolysis occurs in the mitochondria.

II.            The end products of glycolysis are two pyruvic acid molecules together with two packets of ATP.

III.            Enzyme that is used to convert glucose-6-phosphate into fructose 6 phosphate is hexose

IV.            Enzyme that converts fructose 1,6- bisphosphate into glyceraldehyde 3 phosphate is adolase

a)      I, II

b)      II,III

c)      II,IV

d)     None of the above

Glycolysis can be fun…?

Glycolysis

Hey everyone, it’s been 5 weeks since I discussed Cells with you. Now I am here to make Glycolysis your new best friend! Yes, you know I am kidding… Or am I… *evil laugh* lol. Besides, if there is one thing Richie likes to do it is to make you understand and I assure you, you won’t be clicking that little white x in that red box at the top of your screen any time soon!

glycolysis factory

 

Steps in Glycolysis

Steps in Glycolysis

 

Glycolysis is a group of 10 intracellular (cytoplasmic) chemical reactions that makes up the most ancient metabolic pathway to synthesize pyruvate and other chemicals that include the energy currency, ATP, for the cell’s existence… How interesting!  Glycolysis literally means the splitting of 6 carbon glucose into two 3 carbon pyruvates. It is important to understand that it occurs in the cytoplasm and NOT THE MITOCHONDRIA. Yes, I know a lot of people who didn’t grasp this concept from A-levels. 😛 Furthermore, very primitive bacteria that lived in the geological time period when the planet was an anaerobic environment employed this pathway. How cool is that! The first five of the 10 metabolic reactions (in sequence) can be described as vitally investing energy in the form of ATP. The other five reactions produce a surplus, in other words a profit is achieved which ensures that the process of glycolysis doesn’t defeat the purpose of respiration which is to supply an organism with energy as there is a net gain in ATP.

Unfortunately, this is the end of the unpretentious, bigger picture of the process 😦

Worried man

However I will try my best to make you grasp the concepts of each reaction! 🙂

relieved

I assure you, the names of the involved enzymes are the toughest aspect of glycolysis, and learning the stages will be much more fun if you keep that into consideration. Here is a little tip: try learning it without the intimidating names of the enzyme catalysts first! So…. HERE WE GO!

The first reaction is a phosphorylation reaction that involves adding a phosphate (from an ATP) to the 6th carbon atom of glucose to create the structures, glucose-6-phosphate and ADP. This irreversible stage is called the first priming reaction and the enzyme that catalyzes it is called Hexokinase. The biological significance is to trap glucose within the cell since there are no channel proteins capable of transporting this modified form of glucose across the plasma membrane.

'Glucose' trapped in a 'Cell' lol

‘Glucose’ trapped in a ‘Cell’ lol

In the second reaction (a reversible reaction), the enzyme Phosphohexose isomerase converts the aldose sugar glucose-6-phosphate into its ketose isomer, fructose-6-phosphate.

The third reaction is in fact the irreversible second priming reaction, where fructose-6-phosphate is converted into fructose-1,6-bisphosphate (Regina Bailey. 2014), when a phosphate from another molecule of ATP is added to its first carbon via the enzyme Phospho-fructokinease-1 (PFK 1). As seen in the product’s name (fructose-1,6-bisphosphate), ‘bis’ implies that both phosphates are attached to different carbon atoms. Indeed, as we have seen, in the first priming reaction, the phosphate was added to carbon 6, while in this reaction the second phosphate was added to carbon 1. (Don’t say diphosphate!!!)

In the fourth reaction (reversible), the enzyme Aldoses catalyzes a lysis reaction, where the fructose-1,6-bisphosphate is split into glyceraldehyde-3-phosphate and dihydroxyacetone-phosphate (DHAP) (Regina Bailey. 2014). The products that are synthesized are isomers of each other. They are both Triose sugars!

"Glucose" starring Van Damme doing the splits

“Glucose” starring Van Damme doing the splits

halfway there

Halfway through the process!

The fifth reaction, rapidly catalyzed by the enzyme Triose phosphate isomerase brings about the conversion of dihydroxyacetone-phosphate (DHAP) into a glyceraldehyde-3-phosphate. This reaction occurs very quickly because at the instant when the enzyme binds with the substrate, the intermediate formed is so highly unstable, that it is quickly converted into its product. Consequently, Triose phosphate isomerase is considered a kinetically perfect enzyme. You can now see that at the end of the ‘energy investing phase’ that 2 ATPs were used in phosphorylation reactions, while two glyceraldehyde-3-phosphate molecules were synthesized.

Fun fact!: All enzymes of glycolysis has induced fit structures!!!

redox is coming

The sixth step (or the first in the ATP generating phase) involves converting the two glyceraldehyde-3-phosphates into two 1,3-Bisphosphoglycerates. To achieve this, the enzyme Glyceraldehyde 3-phosphate dehydrogenase oxidizes the glyceraldehyde-3-phosphates (removes a hydrogen from each) and the co enzyme NAD+ collects the hydrogen and becomes reduced (NADH). The formation of NADH is essential for glycolysis to continue. The oxidation of the glyceraldehyde-3-phosphate fulfills the energy requirements for the same enzyme, Glyceraldehyde 3-phosphate dehydrogenase, to catalyze a phosphorylation reaction where an inorganic phosphate is added to the oxidized glyceraldehyde-3-phosphate to create the final product 1,3-Bisphosphoglycerate. Remember that in this stage, two 1,3-Bisphosphoglycerates are produced! In other words, a hydrogen is removed from each glyceraldehyde-3-phosphate and it forms NADH. A phosphate is then added to each modified glyceraldehyde-3-phosphate, to form the product 1,3-Bisphosphoglycerate.

In the seventh reaction, two molecules of ATP are being synthesized in a process known as Substrate Level Phosphorylation. The enzyme Phosphoglycerate Kinase removes a phosphate from the first carbon of each of the two 1,3-Bisphosphoglycerates and then these high energy phosphate groups are combined with ADP molecules to create two ATP. Once the phosphates have been removed, the molecules are now called 3-Phosphoglycerates.

The 3-Phosphoglycerates then undergo ‘change in structure’ when the enzyme Phosphoglycerate mutase converts them firstly to 2,3-bisphosphoglycerates (intermediates). Furthermore, the phosphate on carbon 3 is then removed hence two 2-Phosphoglycerates are formed.

changing shape

A 3-Phosphoglycerate undergoes a change in structure

In the ninth reaction, the two 2-Phosphoglycerates are converted into two Phosphoenolpyruvates (PEP) due to the loss of water (dehydration reaction) catalyzed by the enzyme, Enolase.

Finally, the last reaction!!!

yes-finally-pl-ffffff

You guessed it, here the two PEPs are converted into two pyruvates and two more ATP are being synthesized from ADPs. Pyruvate Kinase is the enzyme catalyzing this reaction. It removes the phosphates from the PEPs, and adds it to the ADPs.  This reaction releases a lot of energy in addition to what is stored in the ATPs. This energy is released as heat. It partly contributes to making you perspire during exercise. The two ATPs produced in this final step can be referred to as the energy/ATP profit gained from glycolysis.

Yay! Now we have two pyruvates. That’s pretty cool, but wouldn’t it be cooler if we knew what happens to each pyruvate after synthesis? It will be my pleasure to briefly discus three of these ‘fates’ with you.  🙂

Let us first observe the metabolic pathway in aerobic conditions. Once oxygen is present, the pyruvate is converted to Acetyl CoA. This pathway is called the Link Reaction since it connects Glycolysis to the Krebs cycle. Converting pyruvate into Acetyl CoA is a decarboxylation reaction. The removal of carbon dioxide would lead to a two carbon structure; simultaneously an NAD+ is reduced and the rest of the pyruvate is combined with Coenzyme-A to form Acetyl CoA.

Lactate Fermentation results  from  high physical activity

Lactate Fermentation results from high physical activity

In anaerobic conditions, Lactate fermentation (in animals) or ethanol production (in yeast and plants), are possible scenarios (Myda Ramersar 2011). Lactate fermentation mostly occurs in erythrocytes (red blood cells) and skeletal muscle. Red blood cells lack mitochondria therefore the Krebs cycle and Oxidative phosphorylation cannot occur (rendering the Link reaction useless). Consequently, glycolysis is the sole means for the cells to acquire their energy. Skeletal muscle cells, conversely, respire anaerobically only when oxygen availability is minimal. Since each cell contains a fixed amount of oxidized NAD+, once all of it is reduced by glycolysis, the process will come to a grinding halt. Imagine how bad that would be for your poor cells. 😦 Luckily the process of lactate fermentation (catalyzed by the lactate dehydrogenase enzyme) reconverts NADH into NAD+ by the following generalized equation:

pyruvate + NADH –> lactate + NAD+

Ethanol fermentation in a breadshell

Ethanol fermentation in a breadshell

You can see that the product of glycolysis (pyruvate) is involved in securing its continued synthesis!!!

In the production of ethanol for commercial wine/beer brewing, a fermentation pathway that involves the use of yeast’s ability to respire anaerobically, is utilized. This pathway incorporates the pyruvate first being converted into acetaldehyde by the enzyme pyruvate decarboxylase, and then to ethanol by the enzyme ethanol dehydrogenase. In the latter stage, NADH is oxidized hence glycolysis can continue! Oh and I am sure you guessed it, bread making also incorporates fermentation by yeast. 🙂 Did you realize the amount of science that is involved in making the dough rise? Mind boggling right!

I hope you follow my tip when studying glycolysis. It helps to get the general idea and then work on the details of the process. It helped me 🙂 I would like to take this time to thank you for reading our posts, attempting the MCQ and word search puzzle. Feel free to leave comments and for any post you wish, especially for the MCQ 🙂 The Biochemistry3RST team would love to know if we helped boost your understanding of any topic we blogged on! This might be my last reflection, but I am not abandoning you in your Biochem Jungle 😛 there is more to come. 🙂 Until next time guys! Time for me to rock and roll outa here! Richie, over and out!!!

my-job-here-is-done

References:

· Bailey, Regina. 2014. “10 Steps of Glycolysis”. Accessed March 9th, 2014.                                                                              http://biology.about.com/od/cellularprocesses/a/aa082704a.html

Ramersar, Myda, Mary Jones, Geoff Jones. 2011. Biology for CAPE Unit 1. Cambridge: Cambridge University Press.

Picture References:

Glycolysis Cycle- http://cnx.org/content/m44442/latest/Figure_07_07_02.jpg

Bad time-http://biochemicalminds.files.wordpress.com/2014/03/438e532c9e230ecc312a6c59d925469876c4d3b7b625269fe843155b755b3c55.jpg

Glycolysis Factory- http://dynamic.pixton.com/comic/t/a/6/q/ta6qxsk7epuocem8_v2_.png

Worried man- http://thumbs.dreamstime.com/z/worried-business-man-1741735.jpg

relieved- http://i.imgur.com/RkFZOm0.jpg

prison- http://img.naij.com/n/0b/3/prison-cube_1_.jpg

epic split- Van Damme http://static.squarespace.com/static/51b3dc8ee4b051b96ceb10de/t/52857605e4b0975b1b06bd27/1384478226902/jean-claude-van-dammes-epic-truck-splits-stunt.jpg

redox- http://cdn.memegenerator.net/instances/400x/37209536.jpg

halfway there- https://i.chzbgr.com/maxW500/7762225664/hB8C603B1/
changing shape- http://www.capstoneclassroom.com/product/covers_lg/9781432932763.jpg

FINALLY- http://www.chesnok.com/daily/wp-content/uploads/2013/10/yes-finally-pl-ffffff.jpeg

Link reaction- http://www.revisionworld.com/sites/revisionworld.com/files/rw_files/LinkReaction.JPG

running- http://www.dailyhiit.com/hiit-blog/wp-content/uploads/2013/10/running-wallpaper-41.jpg

breadshell- http://media.tumblr.com/bfa7ee6595e07c7553f6e3372f7ee1d8/tumblr_inline_mpd9c5Kekm1qz4rgp.jpg

My job is done- http://www.troll.me/images/the-chuck-norris/my-job-here-is-done.jpg