glycolysis and TCA Flashcards
(35 cards)
is glucose reduced or oxidized
highly reduced- oxidation is employed in glycolysis to gain energy
Why is glycolysis important
glycolytic breakdown of glucose is the major source of energy of RBCs and sperm, and provides energy to tissues when O2 delivery is limited, such as during exercise
phases of glycolysis
- energy investment phase/ preparatory phase- 2 ATP are used to activate glucose leading to generation of glyceraldehyde-3-P. 2. Payoff phase- energy is extracted for use
How does glucose enter cells
glucose transporters. Insulin sensitive tissues (skeletal muscle and adipose tissue): Glut4 increases glucose transport into the cell following exposure to insulin. Insulin dependent tissues (liver): Glut 2 does not change in response to insulin
List the three types of rxns that occur in glycolysis
- Degradation of the carbon skeleton of glucose to yield pyruvate. 2. substrate level Phosphorylation of ADP to ATP. 3. Generation of NADH
describe reaction 1 of glycolysis
Hexokinase or glucokinase catalyzes activation of D-glucose into glucose-6-phosphate, using first ATP. Ireversible rxn which traps glucose in cell (negative charge), conserves metabolic energy and lowers activation energy of next rxn
hexokinase vs glucokinase
hexokinase 1: not very selective, present in all cells, low Km for sugars and inhibited by glucose-6-P. Glucokinase: selective for glucose, located in liver and pancreatic beta cells, high Km for glucose, inhibited by fructose-6-P
compare carb metabolism in muscle vs liver
liver has Glut2 which maintains glucose conc close to that in the blood. Since glucokinase converts glucose to glu-6-P, this favors net flux of glucose into liver during fed state and net efflux during fasting. When glu is low, glucokinase activity is lower which favors delivery of glu to peripheral tissues containing hexokinase. muscle consumes glu and uses it for energy.
rate limiting step of glycolysis
Reaction 3: fructose-6-phosphate converted to fructose 1,6-bisphosphate by Phosphofructokinase 1 using second ATP. This is the committed step of glycolysis and is irreversible
properties of phosphofructokinase 1
allosteric enzyme- ATP or citrate inhibits the enzyme while AMP stimulates it. The most potent activator of PFK1 is fructose 2,6-bisphosphate which is produced by phosphofructokinase 2 from fructose-6-phosphate
properties of phosphofructokinase 2
Converts fructose-6-phosphate to fructose 2,6 bisphosphate which activates PFK1 (glycolysis) and inhibits fructose 1,6 bisphosphatase (gluconeogenesis). This enzyme is bifunctional- can be a kinase or phosphatase
compare actions of phosphofructokinase during fed and fasting states
Fed: High insulin and low glucagon increase F2,6BP and incrase glycolysis. Fasting: low insulin and high glucagon activates protein Kinase A > phosphorylates PFK-2 which turns into fructose 2,6 bisphosphatase > transforms F 2,6 BP into F6P > inhibits glycoslysis and promotes gluconeogenesis.
describe the first step in energy generating phase of glycolysis
Glyceraldehyde-3-phosphate + 2 NAD+ + Pi (2) 1,3-bisphosphoglycerate + 2NADH + 2H+. Catalyzed by glyceraldehyde-3-phosphate dehydrogenase this is the first oxidation rxn and the first NADH generated
describe the first substrate level phosphorylation of glycolysis
rxn 5: 1,3-Bisphosphoglycerate + 2ADP –> 2 3-phosphoglycerate + 2 ATP. Catalyzed by phosphoglycerate kinase. At this step, net ATP yield is 0 b/c 2 have been made and 2 have been used.
describe the second substrate level phosphorylation of glycolysis
2 phosphoenol pyruvate + 2ADP –> 2 pyruvate + 2ATP. Catalyzed by pyruvate kinase. Now there is net yield of 2 ATP for each molecule of glucose
What inhibits pyruvate kinase
ATP, alanine, and protein kinase A. This promotes gluconeogenesis and inhibits glycolysis when there is sufficient cellular energy
pyruvate kinase deficiency
Second most common cause (after Glucose-6-Phosphate Dehydrogenase deficiency) of enzyme deficiency-linked hemolytic anemia. Normally, Glucagon results in activated protein kinase A which phosphorylates pyruvate kinase and turns off glycolysis.
fates of pyruvate
In presence of O2 and mitochondria: oxidation to Acetyl CoA. Hypoxic/ no mitochondria conditions: pyruvate is converted to lactic acid then heart muscle converts lactate to pyruvate which is then oxidized. Lactate dehydrogenase catalyzes pyruvate/lactate interconversion
Alternative fates of pyruvate in fed vs fasting state (aerobic environment)
fed: converted to alanine, or in cases of excess carb intake can enter mitochondria and increase amount of Acety CoA available for fatty acid synthesis. Fasting: in liver, pyruvate (from lactate) is converted to oxaloacetate and used for gluconeogenesis.
How does pyruvate enter TCA cycle
Pyruvate is transported from cytoplasm into mitochondria where Pyruvate dehydrogenase catalyzes pyruvate transformation into acetyl CoA. (aerobic conditions)
pyruvate dehydrogenase components
Made of 3 enzymes and five coenzymes (coenzyme A, thiamine pyrophosphate (TPP), prosthetic groups, flavin adenine dinucleotide (FAD), nicotinamide adenine, dinucleotide (NAD), and lipoate)
Vitamins involved in pyruvate dehydrogenase cofactors
thiamine (Vit B1) TPP riboflavin (Vit B2) FAD niacin NAD pantothenate coenzyme Athiamine (Vit B1) TPP riboflavin (Vit B2) FAD niacin NAD pantothenate coenzyme A
thiamine deficiency
Wernickes encephalopathy- inability to oxidize pyruvate due to thiamine deficit. Affects brain most b/c this organ derives most of its energy from aerobic oxidation of glucose.
regulation of pyruvate dehydrogenase
allosteric regulation - AMP, CoA and NAD+ activate it. ATP, NADH deactivate it. Second level occurs by phosphorylation of PDH by protein kinase which inactivates PDH, or de-phosphorylation of PDH by phospho-protein phosphatase which activates PDH. calcium activates the phosphatase
