Fates of Pyruvate Biochemistry > Carbohydrate Metabolism > Carbohydrate Metabolism KEY FATES OF PYRUVATE 1. Acetyl CoA: substrate for citric acid cycle and fatty acid synthesis 2. Oxaloacetate: intermediate in CAC and substrate for gluconeogenesis 3. Lactate: produced by eukaryotes in absence of oxygen 4. Ethanol: produced by yeast and some bacteria (including intestinal flora) in absence of oxygen. AEROBIC CONDITIONS 1. Cellular respiration: Pyruvate converts to acetyl CoA • Fed conditions (glucose abundant) • Occurs in mitochondrial matrix • Pyruvate dehydrogenase complex • Irreversible reaction: produces 1 CO2 and 1NADH • Acetyl CoA enters the citric acid cycle and oxidative phosphorylation • Final product is ATP 2. Gluconeogenesis: Pyruvate converts to oxaloacetate • Fasting conditions (glucose in demand) • Occurs in liver (minor process in kidneys): mitochondrial matrix • Pyruvate carboxylase • Irreversible reaction • Oxaloacetate is substrate for gluconeogenesis and CAC intermediate ANAEROBIC CONDITIONS 3. Lactic acid fermentation (humans) • Occurs in exercising muscle and red blood cells: cytosol • Glycolysis: 1 glucose = 2 pyruvates + 2 ATP + 2 NADH • Lactate dehydrogenase: 2 pyruvate + 2NADH = 2 lactate + 2 NAD+ • Reversible reaction • Lactate can enter bloodstream and travel to liver: lactate dehydrogenase catalyzes reverse reaction (lactate to pyruvate) Clinical correlation: intense exercise can produce lactic acidosis; lactate accumulates in muscle cells and causes intracellular drop in pH 4. Ethanol production (yeast and select bacteria) • Can occur in inteestinal flora • Glycolysis: 1 glucose = 2 pyruvates + 2 ATP + 2 NADH 1 / 6 • 2 step rxn: pyruvate to acetaldehyde to ethanol • Ethanol formation consumes 2 NADH in second step and produces 2 NAD+ for reuse • Irreversible reaction • Fermentation in yeast used to make beer and wine FULL-LENGTH TEXT • Here we will learn the different fates of pyruvate, which is the product of glycolysis. • To begin, start a table so we can list 4 key fates of pyruvate. - Acetyl CoA, which is a substrate for the citric acid cycle and fatty acid synthesis. - Oxaloacetate, which is an intermediate in the citric acid cycle and also a substrate for gluconeogenesis. - Lactate, which is produced by eukaryotes in the absence of oxygen. - Ethanol, which is produced by yeast and some bacteria (including intestinal flora) in the absence of oxygen. We will illustrate the location and function of each of these processes. • To begin, indicate that pyruvate is a three-carbon molecule and that it is formed in the first step of glucose metabolism: glycolysis. - Two pyruvates are formed per glucose molecule, but we will only illustrate one for simplicity. • Show that this occurs in the cytosol. • Show that we categorize the pyruvate fates based on if they are: aerobic or anaerobic, meaning whether they occur in the presence or absence of oxygen. • Next, show that in aerobic conditions (the presence of oxygen), pyruvate has two possible fates: - The first is cellular respiration, which occurs in fed conditions – when glucose is abundant. - The second is gluconeogenesis, which occurs in fasting conditions – when glucose is in demand. Begin with cellular respiration, in which the key fate of pyruvate is acetyl CoA. 2 / 6 • Draw a mitochondrion as follows: - Outer mitochondrial membrane, which is a phospholipid bilayer. - Inner mitochondrial membrane, which comprises invaginations called cristae. It is also a phospholipid bilayer. - Label the intermembrane space, which lies between the membranes. - Label the matrix, which lies within the inner mitochondrial membrane. • Show that pyruvate enters the matrix, where it is converted to acetyl CoA. • Indicate that this is an irreversible reaction, catalyzed by an enzymatic complex called pyruvate dehydrogenase complex. • Illustrate that this reaction also produces one NADH molecule and one carbon dioxide molecule as waste. - Remember, this is actually 2NADH molecules and 2 carbon dioxide molecules per glucose. • Draw a circle of arrows in the matrix to illustrate the citric acid cycle. • Show that acetyl CoA can enter the citric acid cycle. • Next, draw the electron transport chain on the inner mitochondrial membrane. - Indicate that the products of the citric acid cycle can enter the electron transport chain. • Show that the final product is ATP, energy for the cell. - Acetyl CoA is also a substrate for fatty acid synthesis, but we will not describe this here. Next, let's show gluconeogenesis, in which the key fate of pyruvate is oxaloacetate. • Draw a liver, which stores glucose in the body. • Draw a section of mitochondrion: the inner membrane and the matrix. • Show that pyruvate again enters the mitochondrial matrix where it is converted to oxaloacetate. 3 / 6 - Indicate that this is an irreversible reaction catalyzed by pyruvate carboxylase. • Write that oxaloacetate is a substrate for gluconeogenesis. • Write that it is also an intermediate of the citric acid cycle. - Thus, indicate that this pathway also replenishes citric acid cycle intermediates. • This brings us to the final two pathways, which occur in the absence of oxygen: - Lactic acid fermentation (lactate production), which occurs in humans. - Ethanol production, which occurs in yeast and select bacteria. Let's start with lactate production. • Indicate that it occurs in exercising muscle and red blood cells (rbc's). • To begin, draw an exercising muscle cell. - Exercising muscles lack oxygen, which slows down the citric acid cycle and oxidative phosphorylation, and causes NADH to accumulate. How do these cells produce energy? • We have already drawn the answer: glycolysis. Let's redraw glycolysis in the cytosol of the exercising muscle cell. We won't draw it again in the red blood cell, but the same process occurs here. • Indicate that glycolysis breaks down glucose into two molecules pyruvate. • Show that it produces 2 NADH's and 2 ATP's via substrate-level phosphorylation. • Use an arrow to illustrate that pyruvate undergoes lactic acid fermentation in the cytosol. • Draw the product of this process: 2 lactates (one for each pyruvate). 4 / 6 • Illustrate that 2NADH's are consumed in the production of lactate. NAD+ can then be reused in glycolysis. • Thus, the net NADH produced in lactic acid fermentation is 0. The net ATP is 2. • Indicate that this process is catalyzed by lactate dehydrogenase and that it is reversible; it is influenced by the concentration of NADH in the cell. - Thus, high NADH favors lactic acid fermentation. • As a clinical correlation, write that intense exercise can produce lactic acidosis, in which lactate accumulates in muscle cells and causes an intracellular drop in pH. - This can produce cramps. How do we get rid of this excess lactate? • Show that lactate can exit the muscle and enter the bloodstream. • Indicate that it travels to the liver, where it is oxidized back to pyruvate by the same enzyme. - Pyruvate can then enter gluconeogenesis or the citric acid cycle. This brings us to our final pathway: ethanol production. • Draw an intestine to indicate that this can occur in our intestinal flora. • Show that a glucose molecule is in the cytosol. • Show that it undergoes glycolysis to produce two pyruvate molecules. • Again show that 2NADH's and 2ATP's are produced. • Next, indicate that pyruvate reduces to ethanol in a two-step reaction that also occurs in the cytosol. • Show that the intermediate in these processes is acetaldehyde. 5 / 6 • Illustrate that two carbon dioxide molecules are lost (1 per pyruvate) to produce this two-carbon intermediate. • Finally, show that two NADH's are oxidized to produce ethanol in the second step. - NAD+ can then be reused in glycolysis. • Each step requires a different enzyme, which we will not cover here. • Indicate that this reaction is reversible. • Draw a pint-glass to indicate that fermentation in yeast is used to make beer and wine. Powered by TCPDF (www.tcpdf.org) 6 / 6.