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CH2OH GLYCOLYSIS O OH OH OH FERMENTATION GLUCOSE Homolactic OH ATP ADP Kinase CH2O(P) O CH3-C-COO- CH3-C-COO- O OH GLUCOSE-6-P OH CH3-C-COOO O OH OH 2, 3 Butanediolic Isomerase FRUCTOSE-6-P + O CO2 OH ATP ADP Kinase C-CH3 CH3-C FRUCTOSE-1,6 Di-Phosphate O 2NADH 2NAD+ CH2O(P) OH OH CH3-C-C-CH3 OH Acetoin O H Adolase 2NADH 2NAD+ DiOH Acetone Phosphate (3C) P-Glyceraldehyde (3C) OH OH NAD+ NADH2 ADP + Pi ATP H H 1 GLU + 2ATP + 2NAD = 2PYR + 4ATP + 2NADH2 Kinase 2, 3, Butanediol CH3-C-C-CH3 GLYCOLYSIS 1, 3, P-Glyceric acid NET GAIN = 2 ATP 2 P-Glyceric acid x2 Isomerase Isocitric Acid (6C) NAD+ NADH2 Enol Pyruvate ADP + Pi ATP Coenzyme A NAD+ Pyruvate NADH2 CH3-C-COOH Kinase x2 2, 3 Butanediolic Fermentation 2PYR + 2NADH Acetoin + NAD + 2 CO2 +2NADH 2, 3 Butanediol + 2NAD NET GAIN = 4 NAD O O CH2O(P) Ethanolic Fermentation PYR + NADH Acetaldehyde + NAD + CO2 +NADH ETOH + NAD NET GAIN = 2 NAD O CO2 OH ETOH CH3-CH2-OH CH3-C-COO- O CH2OH NAD+ NADH Pyruvate Pyruvate CH3-C-COO- CH2O(P) CO2 Acetaldehyde H CH3-C Pyruvate Ethanolic OH NAD+ NADH Homolactic Fermentation PYR + NADH Lactic Acid + NAD NET GAIN = 1 NAD Lactic Acid H NAD+ NADH Pyruvate CO2 ά Ketoglutarate Acid (5C) COO- -CH2-CH2-C-COOO NAD+ NADH2 Tricarboxylic Acid Cycle (TCA/ Krebs Cycle) Succinyl CoA Citric Acid Acetyl CoA CH3-C-S-CoA O Dehydrogenase CO 2 Oxaloacitic Acid (4C) O COO- -CH2-C-COOO PYRUVATE ACTIVATION GDP+ GTP Malate Acid PYRUVATE ACTIVATION NAD+ NADH2 16 NADH from glycolysis need to be reduced. H Red H Ox +3 +2 FMN Fes +2 +3 H2 Red Ox Red TOTAL GAIN: 8 H+ 2 GTP *First energy-producing step Red Ox Anaerobic phosphorylation endproducts (instead of H2O) Red H Ox H2O CoQ CO2 FAD+ FADH2 Fumorate Acid ELECRON TRANSPORT SYSTEM (RESPIRATION / OXIDATIVE PHOSPHORYLATION Ox MULTIPLY THE ABOVE BY TWO Succinate 2 PYR + 2NAD + 2CoA = Acetyl CoA + 2NADH2 + 2CO2 ETS TCA Acetyl CoA + 3NAD + 1 FAD + 1GTP = 3 NADH + 1FADH2 + GTP + CO2 Cyt b Cyt c Cyt a1 Ox Red Ox H2S NH3 Cyt a3 O2 ADP ATP ADP ATP ATPase ATPase Red ADP ATP ATPase SO4 NO2 GLYCOLYSIS 1 GLU + 2ATP + 2NAD = 2PYR + 4ATP + 2NADH2 NET GAIN = 2 ATP Glycolysis takes place in the cytoplasm. It converts glucose, fructose, or galactose into 2 molecules of pyruvate plus 2 ATP. This process uses NAD (an electron acceptor), which becomes reduced to NADH. We need to get it back to NAD or glycolysis will stop. The pyruvates are then taken to the mitochondria to go through the Kreb’s (TCA) cycle to generate ATP. 2 Glycolysis • Glycolysis is like a gumball machine in the cytoplasm. You put one sugar molecule in, add 2 pennies (ATP) and get out two gumballs (pyruvate). The gumball machine also gives your two pennies back, plus an additional two pennies! It takes money to make money, right? • So now you have an extra 2 pennies to spend on energy, plus the two gumballs that you can take to the mitochondria to convert to 2 more special pennies (GTP) that can only be used for certain games in the body (protein synthesis and gluconeogenesis). 3 Glycolysis • During glycolysis, we have to get rid of a hydrogen (H+), but almost no one wants to carry that burden. • There is a guy named NAD who is willing to accept this burden. When he takes on the H+, he is reduced. If his H+ burden is removed by someone else, he feels good, and is oxidized! • All of NAD’s brothers are also named NAD. It takes 2 NAD brothers to come to the glycolysis gumball machine and take on the burden of the H+. They are now called NADH. • Right now, you need to take your 2 gumballs (pyruvate) to the mitochondria so you can convert them into special pennies. • The two NADH brothers will wait for you to complete the Kreb’s Cycle, so you can escort them to the Electron Transport Chain, where their H+ burdens will be lifted. 4 Kreb’s Cycle or Citric Acid Cycle or Tricarboxylic Acid Cycle (TCA) Acetyl CoA + 3NAD + 1 FAD + 1GTP = 3 NADH + 1FADH2 + GTP + CO2 MULTIPLY THE ABOVE BY TWO TOTAL GAIN: 8 H+ and 2 GTP This occurs in the mitochondria, and requires oxygen. It takes pyruvate from glucose, and acetate (in the form of Acetyl CoA) from carbohydrates, fats and proteins, and generates 2 GTP (similar to ATP). The waste product is carbon dioxide. Like glycolysis, it uses NAD and reduces it to NADH. The NADH is then sent to the Electron Transport System so it can be converted back to NAD so glycolysis can continue. 5 Kreb’s Cycle • Now you have taken your two gumballs from glycolysis (pyruvate) and entered the mitochondria. • You see your neighbor, who does not use sugar. He only deals with Acetyl CoA, which he gets from the breakdown of carbohydrates, fats and proteins elsewhere in the body. • You put one of your pyruvate gumballs into a Kreb machine, along with one of his Acetyl CoA molecules. • Three more NAD brothers, plus their cousin FAD have to come in to bear the burdens of the four H+ that will be generated. 6 Kreb’s Cycle • For all this, you will get only one special penny (GTP). Since you have two gumballs, do it again. • You will now have two special pennies, but you now have 8 new people who are carrying your H+ burden, in addition to the 2 people who are waiting for you at the door from the gumball machine. • You need to take all of them to the Electron Transport Chain so someone else can lift their burden and they can get back to work at the gumball machine again. 7 The Electron Transport System (aka oxidative phosphorylation, or cellular respiration) takes the NADH molecules from glycolysis and the TCA cycle and reduces them back to NAD so glycolysis can continue. It also generates more ATP. When this system is performing in the presence of oxygen, oxygen is consumed and the waste product is water. When it is done anaerobically (such as in some bacteria), sulfate is used and the waste product is hydrogen sulfide (will show a black precipitate on culture media) or nitrite is used and the waste product is ammonia. 8 Electron Transport Chain (cellular respiration) • When the NADH brothers enter this area of the mitochondria, they have to walk through a hallway lined with many people that want to shake their hand. • When they finally get to the end of the line, they are greeted by the heavenly oxygen angel. She is so strong, she can take and hold 2 burdens at once. • When she takes the H+ burden from two NADH brothers, she becomes water. The water will be exhaled. We need to inhale some more heavenly oxygen angels to keep this process going. • Now the NAD brothers have been oxidized. They feel so good, they want to go back to work to help again with 9 bearing the H+ burden. What if there is no more oxygen? • Some bacteria, molds, and yeasts can still use the ETC when there is no oxygen. At the end of the handshaking line, they have either sulfate or nitrate. • If they have sulfate, instead of taking the H+ and turning into water to be exhaled, it turns into hydrogen sulfide (H2S), a waste product which shows up as a black color on a Petri dish. • If they have nitrate, they will turn into ammonia, a waste product which has a high pH. 10 What if there is no more oxygen? • Humans do not have sulfate or nitrate. They can only use oxygen as the final electron acceptor in the electron transport chain (cellular respiration). • Muscle cells use a lot of energy, so they are able to run out of oxygen yet still carry out cellular respiration by using fermentation to take the H+ burden off the NAD brothers so they can go back to work for the gumball glycolysis machine and the Kreb’s machine. Muscles are the only human cells that can do this. 11 Fermentation Pathways • • • • When no oxygen is present (such as in muscles during sprinting), the NADH molecules that were generated from glycolysis and the TCA cycle cannot use the electron transport chain to be converted back to NAD. Instead, they use one of three fermentation pathways. Homolactic Ethanolic 2, 3, Butanediolic • In the homolactic pathway (used by humans), the H+ from NADH is donated to pyruvate, converting it to the waste product: lactic acid. The NAD has now been regenerated so glycolysis can continue. By breathing heavily, oxygen is added to lactic acid, converting it to glucose. The lactic acid could also be carried by the bloodstream to the liver, where it is converted back to pyruvate. Therefore, increasing circulation and oxygen helps eliminate lactic acid build-up (ultrasound or massage therapy for sore muscles helps). 12 Ethanol Fermentation • The ethanol fermentation pathway also uses glycolysis, but the pyruvate is then converted to ethanol and carbon dioxide. • Yeasts use this pathway to create beer, and cause the rising of bread dough. Ethanolic Fermentation PYR + NADH Acetaldehyde + NAD + CO2 +NADH ETOH + NAD NET GAIN = 2 NAD 13 CH2OH GLYCOLYSIS O OH OH OH FERMENTATION GLUCOSE Homolactic OH ATP ADP Kinase CH2O(P) O CH3-C-COO- CH3-C-COO- O OH GLUCOSE-6-P OH CH3-C-COOO O OH OH 2, 3 Butanediolic Isomerase FRUCTOSE-6-P + O CO2 OH ATP ADP Kinase C-CH3 CH3-C FRUCTOSE-1,6 Di-Phosphate O 2NADH 2NAD+ CH2O(P) OH OH CH3-C-C-CH3 OH Acetoin O H Adolase 2NADH 2NAD+ DiOH Acetone Phosphate (3C) P-Glyceraldehyde (3C) OH OH NAD+ NADH2 ADP + Pi ATP H H 1 GLU + 2ATP + 2NAD = 2PYR + 4ATP + 2NADH2 Kinase 2, 3, Butanediol CH3-C-C-CH3 GLYCOLYSIS 1, 3, P-Glyceric acid NET GAIN = 2 ATP 2 P-Glyceric acid x2 Isomerase Isocitric Acid (6C) NAD+ NADH2 Enol Pyruvate ADP + Pi ATP Coenzyme A NAD+ Pyruvate NADH2 CH3-C-COOH Kinase x2 2, 3 Butanediolic Fermentation 2PYR + 2NADH Acetoin + NAD + 2 CO2 +2NADH 2, 3 Butanediol + 2NAD NET GAIN = 4 NAD O O CH2O(P) Ethanolic Fermentation PYR + NADH Acetaldehyde + NAD + CO2 +NADH ETOH + NAD NET GAIN = 2 NAD O CO2 OH ETOH CH3-CH2-OH CH3-C-COO- O CH2OH NAD+ NADH Pyruvate Pyruvate CH3-C-COO- CH2O(P) CO2 Acetaldehyde H CH3-C Pyruvate Ethanolic OH NAD+ NADH Homolactic Fermentation PYR + NADH Lactic Acid + NAD NET GAIN = 1 NAD Lactic Acid H NAD+ NADH Pyruvate CO2 ά Ketoglutarate Acid (5C) COO- -CH2-CH2-C-COOO NAD+ NADH2 Tricarboxylic Acid Cycle (TCA/ Krebs Cycle) Succinyl CoA Citric Acid Acetyl CoA CH3-C-S-CoA O Dehydrogenase CO 2 Oxaloacitic Acid (4C) O COO- -CH2-C-COOO PYRUVATE ACTIVATION GDP+ GTP Malate Acid PYRUVATE ACTIVATION NAD+ NADH2 16 NADH from glycolysis need to be reduced. H Red H Ox +3 +2 FMN Fes +2 +3 H2 Red Ox Red TOTAL GAIN: 8 H+ 2 GTP *First energy-producing step Red Ox Anaerobic phosphorylation endproducts (instead of H2O) Red H Ox H2O CoQ CO2 FAD+ FADH2 Fumorate Acid ELECRON TRANSPORT SYSTEM (RESPIRATION / OXIDATIVE PHOSPHORYLATION Ox MULTIPLY THE ABOVE BY TWO Succinate 2 PYR + 2NAD + 2CoA = Acetyl CoA + 2NADH2 + 2CO2 ETS TCA Acetyl CoA + 3NAD + 1 FAD + 1GTP = 3 NADH + 1FADH2 + GTP + CO2 Cyt b Cyt c Cyt a1 Ox Red Ox H2S NH3 Cyt a3 O2 ADP ATP ADP ATP ATPase ATPase Red ADP ATP ATPase SO4 NO2 ATP • Adenosine triphosphate (ATP) is used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. • ATP transports chemical energy within cells for metabolism. It is one of the end products of phosphorylation and cellular respiration and used in many cellular processes, including muscle contraction, motility, and cell division. • One molecule of ATP contains three phosphate groups which provide energy. When ATP is used, it loses a phosphate and is reduced to ADP (diphosphate). • Metabolic processes that use ATP as an energy source convert it back into its precursors. ATP is therefore continuously recycled. • Guanosine triphosphate (GTP) is similar to ATP but can only be used as a source of energy for protein synthesis and gluconeogenesis. 15 ATP Molecule 16