Chapter 9: Carbohydrate metabolism I: Glycolysis, glycogen, gluconeogenesis, and the pentose phosphate pathway Flashcards
The MCAT is most likely to test you on the rate limiting enzymes for each process and these are some examples:
Glycolysis: Phosphofructokinase- 1
Fermentation: lactate dehydrogenase.
Glycogenesis: Glycogen synthase.
Glycogenolysis: Glycogen phosphorylase.
Gluconeogenesis: Fructose-1,6 bisphosphatase.
Pentose phosphate pathway: Glucose-6-Phosphate dehydrogenase.
Oxidation and reduction reactions.
Oxidation is increased bond to oxygen or other heteroatoms on paper and thesis atoms besides carbon and hydrogen) and reduction is increased bond to hydrogen.
There are 4 glucose transporters called GLUT 1 through GLUT 4.
GLUT 2 is in hepatocytes and pancreatic cells. It captures the excess glucose primarily for storage. Much of the remainder bypasses the liver and enters the peripheral circulations. The Km of GLUT 2 is quite high, approximately 15 mM. The liver will pick up excess glucose and store it preferentially after a meal when blood glucose levels are high.
GLUT 4 in adipose tissue and muscle and response to the glucose concentration in peripheral blood. The rate of glucose transport in these two tissues is increased by insulin Which stimulates the movement of additional GLUT 4 transporter to the membrane by a mechanism involving exocytosis. The Km of GLUT 4 is close to normal glucose levels in the blood. This means that the transporter saturated when blood glucose levels are just a bit higher than normal. When a person has high blood sugar concentrations, this transporters will still permit only a constant rate of glucose influx because they will be saturated. By increasing the number of GLUT 4 transporter their surface. Although basal levels of transport occur in all cells independently of insulin, the transport rate increases in adipose tissue and muscle when insulin levels rise.
Glycolysis
Cytoplasmic pathway that converts glucose into two pyruvate molecules. Releasing a modest amount of energy captured into substrate level phosphorylations and one oxidation reaction.
In the liver, glycolysis, the part of the process by which exit glucose is converted to fatty acid for storage.
What happens in red blood cells?
Red blood cells extrude their mitochondria during development. This helps them carry out their functions, which is carrying oxygen in two ways: Maximizing volume available for hemoglobin, the primary oxygen carrying protein. Stopping the red blood cell from utilizing the oxygen it’s supposed to be carrying to oxygen depleted bodily tissues.
Hexokinase and Glucokinase.
The first step in glucose metabolism in any cell are transport across the membrane and phosphorylation by kinase enzymes inside the cell to prevent glucose from leaving the transporter. Glucose entered the cells by facilitated diffusion or active transport. These kinases convert glucose to glucose 6 phosphate.
Hexokinase
Widely distributed in tissues and is inhibited by its product glucose 6 phosphate. It traps the glucose inside the cell.
Glucokinase.
Found only in the liver cells and patriotic cells. In the liver, glucokinase is induced by insulin. He has a high Km.
Pyruvate kinase.
Catalyzes the substrate level phosphorylation of ADP using the high energy substrate phosphoenolpyruvate. It’s activated by fructose 1, 6-bisphosphate from the PFK-1 reaction. This is referred to as feed for activation, meaning that the product of the early reaction of glycolysis simulates a later reaction in glycolysis.
Phosphofructokinase (PFK-1 and PFK-2)
It is the rate limiting enzyme and main control point in glycolysis. In this reaction, fructose 6 phosphate is phosphorylated to fructose1,6- biphosphate using ATP. PFK-1 is inhibited by ATP and citrate and activated by AMP.
Insulin stimulates and Glucagon inhibits PFK-1 in hepatocytes via indirect mechanism, involved PFK 2 and fructose 2, 6-biphosphate. Insulin activates phosphofructokinase 2 (PFK 2 ) which converts a tiny amount of fructose 6-phosphate to fructose 2,6-phosphate (F2,6-BP). This activates PFK 1.
Glyceraldehyde 3 phosphate dehydrogenase.
It catalyzes an oxidation and addition of inorganic phosphate to its substrate, glyceraldehyde 3 phosphate. This result in the production of a high energy intermediates 1,3-bisphosphoglycarate and the reduction of NAD + to NADH.
3 Phosphoglycerate kinase.
Transfers the high energy phosphate from 1,3-bisphosphoglycarate To ADP forming ATP and 3-phosphoglycerate. ADP is directly phosphorylated to ATP using a high energy intermediate is referred to as substrate level phosphorylation. This is the only way to produce ATP in anaerobic tissue.
Important intermediates of glycolysis.
Dihydroxyacetone phosphate (DHAP) is used in hepatic and adipose tissue for triglycerol synthesis. It is formed from fructose 1,6-biphosphate and it can be isomerized to glycerol 3-phosphate which can be converted to glycerol. The backbone of triglycerides.
Fermentation.
In the absence of oxygen, lactate dehydrogenase oxidizes NADH to NAD+. Without mitochondria and oxygen, glycolysis would stop when all the available NAD + has been reduced to NADH. By reducing pyruvate to lactate and oxidizing and NADH to NAD+ , lactate dehydrogenase prevents this potential problem from developing. When oxygenation is poor, most cellularity beats generated by anaerobic glycolysis and lactate production increases.
irreversible enzymes.
There are three points that are irreversible in glycolysis. The enzymes are glucokinase/ hexokinase, PFK-1, pyruvate kinase.
Glycolysis in erythrocytes.
Erythrocytes, or red blood cells, are anaerobic, glycolysis represents the only pathway for ATP production, yielding a net of two ATP per glucose. Red blood cells have biphosphoglycerate mutase, which produces 2,3-bisphosphoglycerol (2,3-BPG) from 1,3-BPG in glycolysis. 2,3-BPG Binds allosterically to the beta chains of hemoglobin and decreases its. Affinity to oxygen. This effect of 2,3-BPG It’s been an oxygen dissociation curve for HbA. The right word, shifting the curve is sufficient to allow unloading of oxygen in tissues, but still allows 100% saturation in the lungs. HbF In the fetus has a higher affinity for oxygen than maternal HbA This allows transplacental passage of oxygen from mother to fetus.
Galactose Metabolism.
An important source of galactose in the diets is a disaccharide lactose present in milk. Lactose is hydrolyzed to galactose and glucose by lactase. Once transported into tissues, galactose is phosphorylated by galactokinase, trapping it in the cell. The resulting galactose 1-phosphate is converted to glucose 1-phosphate by galactose 1-phosphate uridyltransferase and epimerase.
Epimerases
Are enzymes that catalyze the conversion of 1 sugar epimer to another.
Fructose Metabolism.
Fructose is found in honey and fruits and as part of the disaccharide sucrose. Sucrose is hydrolyzed by the duodeno brush border enzyme sucrase. The liver phosphorylates fructose, using fructokinase to trap it in the cell. The resulting fructose 1-phosphate is then cleaved into glyceraldehyde and DHAP by aldolase B.
