Glycolysis Lecture Notes PDF

Lippincott’s illustrated reviews Chapter 8 – Page 91 Lecture 19 Glycolysis 1  Specific Objectives By the end of this lecture students can be able to: Understand the glycolytic pathway of glucose. Understand the hormonal regulation of glycolysis...

Lippincott’s illustrated reviews Chapter 8 – Page 91 Lecture 19 Glycolysis 1  Specific Objectives By the end of this lecture students can be able to: Understand the glycolytic pathway of glucose. Understand the hormonal regulation of glycolysis process. 2  Step 0 of glycolysis in all body cells Transport of glucose into cells Glucose cannot diffuse directly into cells, but enters by one of two transport mechanisms: Na+-independent facilitated diffusion transport Na+-monosaccharide co-transporter system 3 against con gardient A. Na+-independent facilitated diffusion transport This system is mediated by a family of 14 glucose transporters in cell membranes. Examples: GLUT-1 is abundant in erythrocytes and blood brain barrier, but is low in adult muscle. GluT-2 is the transporter in liver cells GLUT 2 GLUT-3 is the primary glucose transporter in neurons. Main transporter GLUT-4 is abundant in adipose tissue and skeletal muscle. insulin stimulate 4 GLUT U 5 B. Na+-monosaccharide cotransporter system (SGLT) This is an energy-requiring process that transports glucose “against” a concentration gradient. This type of transport occurs in the epithelial cells of the intestine, Renal tubules, and choroid plexus. 6  120 140 9 7  Glycolysis The glycolytic pathway is employed in cytoplasm of cells in all body tissues for the breakdown of glucose to provide energy (in the form of ATP) and intermediates for other metabolic pathways. Aerobic glycolysis Break down of glucose with enguh oxygen and mitochondria Pyruvate is the end product of glycolysis in cells with mitochondria and an adequate supply of oxygen. End Product 8  Anaerobic glycolysis Conversion of glucose to lactate and can occur without the participation of oxygen. Anaerobic glycolysis allows the production of ATP in tissues that lack mitochondria (for example, red blood cells) or in cells deprived of sufficient oxygen. mucle has mitochondria Exercising 9 but no oxygen only understand 10  Like mitochoquiffy Electro transport chain give 6 ATP 5 ATP Total 10 used 2 am I Earia 11 In case of anaerobic glycolysis 12  Energy yield from glycolysis 1. Anaerobic glycolysis: Two molecules of ATP are generated for each molecule of glucose converted to two molecules of lactate There is no net production or consumption of NADH. ZATP 2 Lactate 13 2. Aerobic glycolysis: The direct consumption and formation of ATP is the same as in anaerobic glycosis_that is, a net gain of two ATP per molecule of glucose. 2 ATP 1 glucose Two molecules of NADH are also produced per molecule of glucose. 2 NADH 3 NADH by the electron transport chain, producing approximately three ATP for each NADH molecule entering the chain. in cytoplasm The net energy released is 8 ATP 174 mitochonde 14 4 in  Hormonal regulation of glycolysis a) Glucagon : is secreted in hypoglycemia or in carbohydrate deficiency. It affects liver cells mainly as follows: It acts as inhibitors for glycolytic key enzymes (glucokinase, Phospho fructokinase -1, pyruvate kinase). To preserve sugar b) Insulin: It is secreted in hyperglycemia and after carbohydrates feeding, it causes: Stimulation of glycolytic key enzymes. 15 To break down  Key enzymes of glycolysis Three enzymes catalyze three irreversible reaction of glycolysis. 1- a-Hexokinase: In most tissues, the phosphorylation of glucose is catalyzed by hexokinase. Attraction Hexokinase has a low Km, therefore, a high affinity for glucose. This permits the efficient phosphorylation and subsequent metabolism of glucose even when tissue concentrations of glucose are low. Hexokinase, however, has a low Vmax for glucose and, therefore, cannot phosphorylate more sugars than the cell can use. 16 17 1- b-Glucokinase: Lowers glucose In liver parenchymal cells and β cells of the pancreas, glucokinase (also called hexokinase D, or type IV) is the predominant enzyme responsible for the phosphorylation of glucose. In β cells, glucokinase functions as the glucose sensor, determining the threshold for insulin secretion. In the liver, the enzyme facilitates glucose phosphorylation during hyperglycemia. 18  Glucokinase has a much higher Km, requiring a higher glucose concentration for half-saturation. Thus, glucokinase functions only when the intracellular concentration of glucose in the hepatocyte is elevated, such as during the brief period following consumption of a carbohydrate-rich meal, when high levels of glucose are delivered to the liver via the portal vein. Glucokinase has a high Vmax, allowing the liver to effectively remove the flood of glucose delivered by the portal blood. 19 2- phospho-fructokinase-1 (PFK-1) PFK-1 is the most important control point and the rate-limiting and committed step of glycolysis. ATP inhibts it PFK-1 is inhibited allosterically by elevated levels of ATP. Elevated levels of citrate, an intermediate in the TCA cycle, also inhibit PFK-1. Conversely, PFK-1 is activated allosterically by high concentrations of AMP, which signal that the cell’s energy stores are depleted. Citrate inhibition favors the use of glucose for glycogen synthesis. 20 3- Pyruvate kinase (PK): It catalyze conversion of phosphoenol pyruvate (PEP) to pyruvate with formation of ATP. Pyruvate kinase deficiency: The normal, mature erythrocyte lacks mitochondria and is, therefore, completely dependent on glycolysis for production of ATP. This ATP is required to meet the metabolic needs of the red blood cell, and also to fuel the pumps necessary for the maintenance of the biconcave, flexible shape of the cell, which allows it to squeeze through narrow capillaries. 21  The anemia observed in glycolytic enzyme deficiencies is a consequence of the reduced rate of glycolysis, leading to decreased ATP production. The resulting alterations in the red blood cell membrane lead to changes in the shape of the cell and, ultimately, to phagocytosis by the cells of the reticuloendothelial system, particularly macrophages of the spleen. The premature death and lysis of red blood cells results in hemolytic anemia. Break down of RBC 22 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 23 Reference Book: Vasudevan, D. M., Sreekumari, S., and Kannan, V.., 2011. Textbook of biochemistry for medical students, 6th Edition. 24