MCAT Biochemistry
Pyruvate is a key intermediate during glycolysis, gluconeogenesis, and aerobic metabolism. It is also needed to synthesize lactate and alanine. In bacteria and yeast, pyruvate produces ethanol by fermentation. During glycolysis, 1 glucose molecule produces 2 pyruvate, 2 NADH, and a net gain of 2 ATP. When oxygen is available, pyruvate enters the mitochondrial matrix, and the pyruvate dehydrogenase complex (PDC) converts pyruvate, NAD+, and CoA into acetyl-CoA, NADH, and CO2. Acetyl-CoA subsequently enters the TCA cycle.
When oxygen is unavailable, lactate dehydrogenase turns pyruvate and NADH into lactate and NAD+. This step is reversible, takes place in the cytosol, and is part of the Cori cycle. Erythrocytes, leukocytes, testis, renal medullary cells, and type 2 skeletal muscle fibers depend on anaerobic glycolysis. During anaerobic glycolysis, 1 glucose produces 2 lactate and 2 ATP. Pyruvate can be directly converted to alanine via alanine transaminase, which is part of the Cahill cycle. When glucose is not immediately available, pyruvate undergoes gluconeogenesis to produce glucose. Lastly, oxygen-deprived bacteria and yeast convert pyruvate into ethanol in a process called fermentation.
Lesson Outline
<ul> <li>Pyruvate is a key intermediate during glycolysis, gluconeogenesis, and aerobic metabolism</li> <li>During glycolysis, 1 glucose produces 2 pyruvate, 2 NADH, and 2 ATP</li> <li><strong>Uses ("Fates") of Pyruvate:</strong></li> <ul> <li>1. Aerobic metabolism (Pyruvate Dehydrogenase Complex)</li> <ul> <li>Occurs when oxygen is available</li> <li>Pyruvate enters the mitochondrial matrix</li> <li>PDC converts pyruvate, NAD+, and CoA into acetyl-CoA, NADH, CO2</li> <li>Acetyl-CoA subsequently enters the TCA cycle</li> </ul> <li>2. Anaerobic glycolysis (Lactate Dehydrogenase)</li> <ul> <li>Occurs when oxygen is unavailable</li> <li>LDH turns pyruvate and NADH into lactate and NAD+</li> <li>This step is reversible, takes place in the cytosol, and is part of the Cori cycle</li> <li>Erythrocytes, leukocytes, testis, renal medullary cells, and type 2 skeletal muscle fibers depend on anaerobic glycolysis</li> <li>During anaerobic glycolysis, 1 glucose produces 2 lactate and 2 ATP</li> </ul> <li>3. Conversion to alanine (Alanine Transaminase)</li> <ul> <li>Pyruvate can be directly converted to alanine via alanine transaminase</li> <li>This step is reversible and is part of the Cahill cycle</li> </ul> <li>4. Gluconeogenesis</li> <ul> <li>Occurs when glucose is not immediately available, like after a prolonged fast</li> <li>Pyruvate undergoes gluconeogenesis to make glucose, via intermediates of oxaloacetate and PEP</li> <li>Pyruvate enters the mitochondrial matrix</li> <li>Pyruvate carboxylase uses ATP to add a CO2 group to pyruvate producing oxaloacetate</li> </ul> <li>5. Fermentation (in bacteria and yeast)</li> <ul> <li>Oxygen-deprived bacteria and yeast convert pyruvate into ethanol</li> <li>This process is called fermentation and is anaerobic</li> </ul> </ul> </ul>
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FAQs
After glycolysis, pyruvate can follow three primary pathways: 1) conversion to lactate through anaerobic fermentation, which occurs under low oxygen conditions; 2) conversion to alanine via transamination, which is commonly observed in muscle cells; and 3) conversion to acetyl-CoA for entry into the TCA cycle, which occurs under aerobic conditions and is an essential step for energy production through aerobic metabolism.
During gluconeogenesis, pyruvate is converted back into glucose. This process primarily takes place in the liver and to some extent in the kidneys. Pyruvate is first converted into oxaloacetate and then into phosphoenolpyruvate (PEP) through a series of enzymatic reactions. Eventually, these intermediates are used to form glucose, which is released into the bloodstream to maintain blood glucose levels during periods of fasting or increased energy demand.
The Cori cycle plays a crucial role in recycling lactate produced in muscles during anaerobic glycolysis. Lactate is transported to the liver, where it is converted back into pyruvate. Pyruvate then enters gluconeogenesis to form glucose, which can be transported back to the muscles to provide energy. Essentially, the Cori cycle enables the conservation and efficient use of glucose and lactate between muscles and the liver during periods of increased energy demand.
Under aerobic conditions, pyruvate is converted to acetyl-CoA by the pyruvate dehydrogenase complex. Acetyl-CoA then enters the TCA cycle (also known as the Krebs cycle or citric acid cycle), where it undergoes a series of oxidation reactions to generate ATP, NADH, and FADH2. These high-energy molecules are further utilized in the electron transport chain to produce additional ATP. Thus, the presence of oxygen and active aerobic metabolism directs pyruvate towards the TCA cycle, promoting efficient energy production.
In muscle cells, pyruvate can be converted to alanine via transamination, a process in which an amino group is transferred from another amino acid, typically glutamate, to pyruvate. This results in the formation of alanine and α-ketoglutarate. Alanine can then be transported to the liver, where it can be converted back to pyruvate and enter gluconeogenesis. This interconversion between pyruvate and alanine acts as a mechanism for muscles to maintain their energy supply and for the liver to regulate glucose levels during periods of increased energy demand.
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