วันอังคารที่ 22 มกราคม พ.ศ. 2551

Cellular respiration

Cellular Respiration:
An analogy can be drawn between the process of cellular respiration in our cells and a car. The mitochondria are the engines of our cells where sugar is burned for fuel and the exhaust is CO2 and H2O. Note that in a car that burned fuel perfectly, the only exhaust should theoretically be CO2 and H2O also.
There are three steps in the process of cellular respiration: glycolysis, the Krebs cycle, and the electron transport chain.
In contrast to fermentation, in the process of cellular respiration, the pyruvic acid molecules are broken down completely to CO2 and more energy released. Note that three molecules of O2 must react with each molecule of pyruvic acid to form the three carbon dioxide molecules, and three molecules of water are also formed to “use up” the hydrogens. As mentioned above, in glycolysis, a total of four molecules of ATP are produced, but two are used up in other steps in the process. Additional ATP is produced during the Krebs Cycle and the Electron Transport Chain, resulting in a grand total of 40 ATP molecules produced from the breakdown of one molecule of glucose via cellular respiration. Since two of those are used up during glycolysis, in prokaryotes a net total of 38 molecules of ATP are produced by cellular respiration. Most prokaryotes have very simple cells which lack several types of organelles present in eukaryotes, and therefore the Krebs Cycle and the Electron Transport Chain occur in the cytoplasm and/or using chemicals embedded in the cell membrane. In contrast, eukaryotes have more complex cells with more specialized organelles to perform given functions. In eukaryotes, the Krebs Cycle and Electron Transport Chain occur within the mitochondria, and thus the pyruvic acid resulting from glycolysis must be sent into the mitochondria for these reactions to occur. However, to move one molecule of pyruvic acid (remember each molecule of glucose turns into two pyruvic acid molecules) from the cytoplasm into a mitochondrion “costs” the cell one molecule of ATP (therefore two ATPs for a whole glucose), thus a net total of 36 ATP molecules per molecule of glucose is produced in eukaryotes as compared to only two in fermentation. The overall reaction for cellular respiration is C6H12O6 + 6O2 6CO2 + 6H2O (+ energy for the cell to use for other things).

Pyruvic Acid + 2 H+
+ 3 O2
3 Carbon Dioxide
+ 3 H2O+ 34 ATP
In glycolysis and the Krebs cycle, there are also a number of electrons released as the glucose molecule is broken down. The cell must deal with these electrons in some way, so they are stored by the cell by forming a compound called NADH by the chemical reaction, NAD+ + H+ + 2e– NADH. This NADH is used to carry the electrons to the electron transport chain, where more energy is harvested from them.
In eukaryotes, the pyruvic acid from glycolysis must be transferred into the mitochondria to be sent through the Krebs cycle, also known as the citric acid cycle, at a “cost” of one ATP per molecule of pyruvic acid. In this cycle, discovered by Hans Krebs, the pyruvic acid molecules are converted to CO2, and two more ATP molecules are produced per molecule of glucose. First, each 3-carbon pyruvic acid molecule has a CO2 broken off and the other two carbons are transferred to a molecule called acetyl coenzyme A, while a molecule of NADH is formed from NAD+ for each pyruvic acid (= 2 for the whole glucose). These acetyl CoA molecules are put into the actual cycle, and after the coenzyme A part is released, eventually each 2-carbon piece is broken apart into two molecules of CO2. In the process, for each acetyl CoA that goes into the cycle, three molecules of NADH, one molecule of FADH2, and one molecule of ATP are formed (= 6 NADH, 2 FADH2, and 2 ATP per whole glucose).
The electron transport chain is a system of electron carriers embedded into the inner membrane of a mitochondrion. As electrons are passed from one compound to the next in the chain, their energy is harvested and stored by forming ATP. For each molecule of NADH which puts its two electrons in, approximately three molecules of ATP are formed, and for each molecule of FADH2, about two molecules of ATP are formed.
Many of the compounds that make up the electron transport chain belong to a special group of chemicals called cytochromes. The central structure of a cytochrome is a porphyrin ring like chlorophyll but with iron in the center (chlorophyll has magnesium). A porphyrin with iron in the center is called a heme group, and these are also found in hemoglobin in our blood.
At the last step in the electron transport chain, the “used up” electrons, along with some “spare” hydrogen ions are combined with O2 (we finally got around to the O2) to form water as a waste product: 4e- + 4H+ + O2 2H2O.
Click on the heme groupto see how to draw one.

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Many of the enzymes in the cells of organisms need other helpers to function. These non-protein enzyme helpers are called cofactors and can include substances like iron, zinc, or copper. If a cofactor is an organic molecule, it then is called a coenzyme. Many of the vitamins needed by our bodies are used as coenzymes to help our enzymes to do their jobs. Vitamin B1 (thiamine) is a coenzyme used in removing CO2 from various organic compounds. B2 (riboflavin) is a component of FAD (or FADH2), one of the chemicals used to transport electrons from the Krebs cycle to the electron transport chain. Vitamin B3 (niacin) is a component of NAD+ (or NADH) which is the major transporter of electrons from glycolysis and the Krebs cycle to the electron transport chain. Without enough of these B vitamins, our ability to get the energy out of our food would come to a grinding halt! B6 (pyridoxine), B12 (cobalamin), pantothenic acid, folic acid, and biotin are all other B vitamins which serve as coenzymes at various points in metabolizing our food. Interestingly, B12 has cobalt in it, a mineral which we need in only very minute quantities, but whose absence can cause symptoms of deficiency.
My mother once had a friend who had porphyria, a dominant genetic disorder in which the person’s body cannot properly make porphyrin rings. This would, thus, affect the person’s ability to make both hemoglobin to carry oxygen in the blood and cytochromes for the electron transport chain. This woman’s symptoms were quite variable. At times, she would appear nearly normal while on other occasions she would have to be hospitalized for temporary paralysis of part of her body or other symptoms. There were a number of foods and drugs she had to avoid because they would trigger or worsen her symptoms. She frequently was in a lot of pain. Because porphyria is a dominant genetic disorder, there was a 50% chance this woman’s daughter would also have porphyria. Thus after the woman was diagnosed with porphyria, a number of tests were also run on the girl, and she was more carefully monitored as she grew up. My mother eventually lost contact with them, so I never heard the end of the story.
Because there are a number of enzymes and steps involved in forming porphyrin rings, there are a number of possible points in the process where genetic defects could occur. The Merck Manual says there are eight steps in the process of making porphyrin rings, with genetic abnormalities possible in seven of the eight enzymes.
Several years ago, Dr. Fankhauser mentioned to me that he heard somewhere that an “average” 70 kg (= 154 lb) person makes about 40 kg (= 88 lb) of ATP/day, which would be 57% of that person’s body weight. As we discussed that, the question arose, “What would be the maximum amount of ATP that a person could possibly make?” To try to come up with an answer to that question, I did the following calculations.
First, let’s assume that person eats an “average” dietary intake of 2500 KCal of food energy (a number listed on the side of many food packages and a reasonable amount that such a person might consume).
However, just out of curiosity, let’s assume that all (100%) of that is glucose (In real life, that would be a terrible idea! We need all the other nutrients that we get from eating a variety of foods.). Since carbohydrates store about 4 KCal of energy per gram, that would mean that 2500 KCal of glucose would be equivalent to 625 g (= 1.4 lb) of glucose. Since the molecular weight of glucose is 180 g/m, this would be equivalent to 3.47 moles of glucose.
Also, just for the sake of argument, let’s assume that 100% of the ingested glucose is burned for fuel, and that the process is 100% efficient so there is no waste (in real life, our bodies would never use all 100% for fuel – some gets used to build other chemicals, and just like the fuel efficiency in our automobiles, the process is never 100% efficient.). Since, as was mentioned above, eukaryotes make about 36 moles of ATP from every mole of glucose, then those 3.74 moles of glucose would be equivalent to 125 moles of ATP.
The molecular weight of ATP is 507 g/m, so that would be 63375 g or 63.375 kg of ATP.
Thus, if it was really possible to meet all of those background assumptions and a 70 kg person really could make 63 kg of ATP, that would be 90% of that person’s body weight! However, to think that we make even 57% – about half – of our body weight each day in ATP is pretty amazing.

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