Fates of Pyruvate

• NADH must be recycled to regenerate NAD+.
• Under aerobic conditions, pyruvate is oxidized to acetyl CoA.
• Under anaerobic conditions or low oxygen conditions (hypoxia), pyruvate is reduced to lactate or ethanol.
• Fermentation is the general term for the processes that extract energy (like ATP) but do not consume oxygen or change the concentrations of NAD+ or NADH.
• Lactic acid fermentation is where pyruvate accepts electrons from NADH and is reduced to lactate while regenerating NAD+ necessary for glycolysis.
• Ethanol (alcohol) fermentation is when pyruvate is further catabolized to ethanol.
• How are glycolysis, ethanol fermentation, and lactate fermentation all related?

  • All are regulated by the ATP/ADP mass action ratio
  • All three produce carbon dioxide
  • All can proceed in the absence of oxygen
  • All require pyruvate
  • All three produce NADH

  All can proceed in the absence of oxygen. Under anaerobic conditions, the pyruvate can be reduced to lactate or ethanol by fermentation. The recycling of NADH to NAD+ in the processes of lactate or alcohol fermentation allow continued glycolysis in the absence of oxygen.
• The Pasteur and Warburg Effects are due to dependence on glycolysis alone for ATP production.
• The Pasteur effect is the effect by which the rate and total amount of glucose consumption under anaerobic conditions is many times greater than under aerobic conditions.
• The Pasteur effect occurs because the ATP yield from glycolysis alone is much smaller, 2 ATP per glucose, than complete oxidation to CO2, 30 to 32 ATP per glucose
• The Warburg effect is the observation that tumor cells have high rates of glycolysis, with fermentation of glucose to lactate, even in the presence of oxygen.
• The Warburg effect is the basis of PET scanning used to diagnose tumors.
• Which statement regarding glycolysis is false?

  • It consists of ten enzyme catalyzed reactions.
  • It is cytosolic
  • It tends to run more slowly in tumor cells
  • It is nearly identical in all organisms

  It tends to run more slowly in tumor cells. The German biochemist Otto Warburg discovered in 1928 that tumors of nearly all types carry out glycolysis at a much higher rate than normal tissue, even when oxygen is available. This Warburg effect is the basis for several methods of detecting and treating cancer.
• Pyruvate is the terminal electron acceptor in lactic acid fermentation.
• Organisms can regenerate NAD+ by transferring electrons from NADH to pyruvate, forming lactate.
• Lactate dehydrogenase catalyzes the reduction of pyruvate to lactate.

  • NADH gets converted to NAD+
  • delta G'degree = -25.1 kJ/mol
• Glycolysis converts 2 NAD+ to 2 NADH and the reduction of pyruvate to lactate regenerates 2 NAD+. So, there is no net change in NAD+ or NADH.
• Lactate is carried in blood to the liver, where it is converted to glucose during recovery.
• Acidification resulting from ionization of lactic acid in muscle and blood limits the period of vigorous activity, such as sprinting.
• Ethanol is the reduced product in ethanol fermentation.
• Yeast and other microorganisms regenerate NAD+ by reducing pyruvate to ethanol and CO2.

  • Pyruvate is converted to acetaldehyde and CO2 by pyruvate decarboxylase, TPP, and Mg2+
  • Acetaldehyde is converted to ethanol and NAD+ by alcohol dehydrogenase and NADH
• The overall equation for ethanol fermentation is:

  • Glucose + 2 ADP + 2 Pi --> 2 ethanol + 2 CO2 + 2 ATP + 2 H2O
• Fermentation is needed for anaerobic glycolysis:

  • Only in organisms that produce ethanol
  • To convert lactate to pyruvate
  • Only in anaerobic organisms
  • To convert NADH to NAD+

  To convert NADH to NAD+. Under aerobic conditions, NADH produced by glycolysis is reoxidized to NAD+ through mitochondrial electron transfer. Under anaerobic conditions, pyruvate fermentation to lactate or to ethanol is required to produce the NAD+ needed for glycolysis to continue.
• Pyruvate decarboxylase catalyzes the irreversible decarboxylation of pyruvate to acetaldehyde. This requires Mg2+ and the coenzyme thiamine pyrophosphate.
• Alcohol dehydrogenase catalyzes the reduction of acetaldehyde to ethanol.
• Thiamine pyrophosphate is a coenzyme derived from vitamin B1.
• The thiazolium ring of TPP plays an important role in the cleavage of bonds adjacent to a carbonyl group.
• TPP dependent reactions include:

  • Pyruvate decarboxylase in ethanol fermentation
  • Pyruvate dehydrogenase alpha-ketoglutarate dehydrogenase in the synthesis of acetyl CoA in the citric acid cycle
  • Transketolase in the carbon assimilation reactions and pentose phosphate pathway.
• What statement regarding fermentation is false?

  • At least one form of fermentation requires an enzyme with a thiamine pyrophosphate coenzyme
  • It requires one enzyme to convert pyruvate to ethanol but two enzymes to convert pyruvate to lactate.
  • Anaerobic glycolysis is coupled to fermentation results in ATP production without any net oxidation or reduction of the glucose carbons.
  • Fermentation produces lactate in heavily exercising muscle.

  It requires one enzyme to convert pyruvate to ethanol but two enzymes to convert pyruvate to lactate.
• Certain microorganisms in food products ferment the carbohydrates and yield metabolic products that give foods their characteristic forms, textures, and tastes.
• The drop in pH from fermentation preserves food from spoilage.
• Fermented foods:

  • Lactobacillus bulgaricus ferments carbohydrates in milk to lactic acid to make yogurt
  • Propionibacterium freudenreichii ferments milk to produce propionic acid and CO2 to make Swiss cheese
  • Others include pickles, sauerkraut, sausage, soy sauce, kimchi. kefir, dahi, and kombucha.
• Ethanol fermentation of carbohydrates in cereal grains by yeast glycolytic enzymes produces beer.
• In brewing beer, why is it necessary to use an enclosed container so O2 can be excluded?

  • Oxygen will react with the ethanol and convert it into ethane
  • Under aerobic conditions, yeast oxidizes the product of glycolysis to CO2 and H2O
  • Lactic acid can build up under aerobic conditions
  • The yeast can only grow anaerobically

  Under aerobic conditions, yeast oxidizes the product of glycolysis to CO2 and H2O. When all the dissolved oxygen in the vat has been consumed, the yeast switches to anaerobic metabolism and ferment sugars to ethanol and CO2.
• Chemical production by fermentation

  • Clostridium acetobutyricum ferments starch to butanol and acetone. This opened the field of industrial fermentations
  • Formic, acetic, propionic, butyric, and succinic acids
  • Ethanol, glycerol, methanol, isopropanol, butanol, and butanediol
  • Penicillin, streptomycin, and chloramphenicol
• Technology developed for large scale production of alcoholic beverages can be applied to the production of ethanol as a renewable fuel.
• Fuel can be produced from relatively inexpensive, and renewable resources