Cellular Respiration and Fermentation

Here’s a song about cellular respiration.

Glycolysis: There are two important ways a cell can harvest energy from food:fermentation andcellular respiration. Both start with the same first step: the process ofglycolysis which is the breakdown or splitting of glucose (6 carbons) into two 3-carbon molecules calledpyruvic acid. The energy from other sugars, such as fructose, is also harvested using this process. Glycolysis is probably the oldest known way of producingATP. There is evidence that the process of glycolysis predates the existence of O2 in the Earth’s atmosphere and organelles in cells: Glycolysis does not need oxygen as part of any of its chemical reactions. It serves as a first step in a variety of both aerobic and anaerobic energy-harvesting reactions. Glycolysis happens in the cytoplasm of cells, not in some specialized organelle. Glycolysis is the one metabolic pathway found in all living organisms.
		glucose 2 pyruvic acid molecules
+ 4 H+ + energy stored in 2 ATP molecules

Fermentation:

In fermentation these pyruvic acid molecules are turned into some “waste” product, and a little bit of energy (only two ATP molecules per molecule of glucose – actually four are produced in glycolysis, but two are used up) is produced. Out of many possible types of fermentation processes, two of the most common types are lactic acid fermentation and alcohol fermentation.
		Pyruvic Acid + 2 H+
			or
		Lactic Acid		Ethanol and Carbon Dioxide

Lactic acid fermentation is done by some fungi, some bacteria like theLactobacillus acidophilus. in yogurt, and sometimes by our muscles. Normally our muscles do cellular respiration like the rest of our bodies, using O₂ supplied by our lungs and blood. However, under greater exertion when the oxygen supplied by the lungs and blood system can’t get there fast enough to keep up with the muscles’ needs, our muscles can switch over and do lactic acid fermentation. In the process of lactic acid fermentation, the 3-carbon pyruvic acid molecules are turned intolactic acid. It is the presence of lactic acid in yogurt that gives it its sour taste, and it is the presence of lactic acid in our muscles “the morning after” that makes them so sore. Once our muscles form lactic acid, they can’t do anything else with it, so until it is gradually washed away by the blood stream and carried to the liver (which is able to get rid of it), our over-exerted muscles feel stiff and sore even if they haven’t been physically injured.

Alcohol fermentation is done by yeast and some kinds of bacteria. The “waste” products of this process are ethanol and carbon dioxide (CO₂). Humans have long taken advantage of this process in making bread, beer, and wine. In bread making, it is the CO₂ which forms and is trapped between the gluten (a long protein in wheat) molecules that causes the bread to rise, and the ethanol (often abbreviated as EtOH – do you remember how to draw it?) evaporating that gives it its wonderful smell while baking. The effects of the ethanol in beer and wine are something with which many college students are familiar (sometimes too familiar?), and it is the CO₂ produced by the process of fermentation that makes these beverages effervescent.

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, theKrebs cycle, and theelectron 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 calledNADH 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 thecitric 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 calledacetyl 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 amitochondrion. 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 calledcytochromes. The central structure of a cytochrome is aporphyrin ring like chlorophyll but with iron in the center (chlorophyll has magnesium). A porphyrin with iron in the center is called aheme 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 group to see how to draw one.

Many of the enzymes in the cells of organisms need other helpers to function. These non-protein enzyme helpers are calledcofactors and can include substances like iron, zinc, or copper. If a cofactor is an organic molecule, it then is called acoenzyme. 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 ofFAD (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, andbiotin 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 hadporphyria, 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.

As another example:
• suppose a person would consume one 12-oz. can of soft drink,
• most types of soft drink contain about 41 to 49 g of sugar, so let’s say this soft drink contains 45 g,
• suppose all of that sugar would be glucose,
• suppose the person’s body burns all of that sugar for fuel and does not store any of it as fat or use any of it in other ways, and
• suppose the process of cellular respiration is 100% efficient and the sugar is completely oxidized to CO₂ and H₂O.
Then:
• since the molecular weight of glucose is 180g/m, the 45 g of glucose would be 0.25 m,
• since cellular respiration produces 36 m ATP for each 1 m of glucose, that would make 9 m of ATP, and
• since the MW of ATP is 507 g/m, that would be equivalent to 4563 g (about 10 lb) of ATP.

Recently I received an e-mail message from a student who asked how long the whole process takes. While I have never seen any information on that in print, a rough approximation can also be calculated from the above statistic:

• If, as mentioned above, an “average” 70 kg person makes about 40 kg of ATP/day, then
  40 kg/24 hr × 1 hr/60 min × 1000 g/kg = about 27.8 g/min.
• Since the molecular weight of ATP is 507 g/m, then
  that 27.8 g/min × 1 m/507 g = 0.0548 m/min.
• Avagadro’s number says that there are always 6.02 x 10²³ molecules/mole,
  so 0.0548 m/min × 6.02 x 10²³ molecules/mole = 3.30 x 10²² molecules/min.
• or, since there are 60 sec/min, then that’s
  3.30 x 10²² molecules/min × 1min/60 sec = 5.50 x 10²⁰ molecules/sec made by a 70 kg body.
• so that would be equivalent to
  5.50 x 10²⁰ molecules/sec ÷ 70 kg = 7.85 × 10¹⁸ molecules/sec/kg of body
• or × 1kg/1000 g = 7.85 × 10¹⁵ molecules/sec/g of body
• or × 1g/1000 mg = 7.85 × 10¹² molecules/sec/mg of body
• or × 1mg/1000 µg = 7.85 × 10⁹ molecules/sec/µg of body.

References:

• Berkow, Robert, ed. 1999. The Merck Manual. 17th ed. Merck, Sharp & Dohme, Rahway, NJ.
• Borror, Donald J. 1960. Dictionary of Root Words and Combining Forms. Mayfield Publ. Co.
• Campbell, Neil A., Lawrence G. Mitchell, Jane B. Reece. 1999. Biology, 5^th Ed.   Benjamin/Cummings Publ. Co., Inc. Menlo Park, CA. (plus earlier editions)
• Campbell, Neil A., Lawrence G. Mitchell, Jane B. Reece. 1999. Biology: Concepts and Connections, 3^rd Ed.   Benjamin/Cummings Publ. Co., Inc. Menlo Park, CA. (plus earlier editions)
• Marchuk, William N. 1992. A Life Science Lexicon. Wm. C. Brown Publishers, Dubuque, IA.