Introduction to glucose metabolism

Overview of glucose metabolism

Objectives critical importance of glucose Recognizing the critical importance of glucose as the main carbohydrate of blood & main fuel of human cells. glucose transport Recognizing glucose transport into cells sources of blood glucose Recalling the sources of blood glucose in feed & fasting states. basic concepts & directions (pathways) of metabolism. Understand the basic concepts & directions (pathways) of metabolism.

General importance of carbohydrates in human body Provide energy 1- Provide energy through metabolism pathways and cycles Store energy 2- Store energy in the form of: starch (in plants) glycogen (in animals and humans) Supply carbon 3- Supply carbon for synthesis of other compounds. Form structural components 4- Form structural components in cells and tissues.

A constant source of GLUCOSE is an absolute requirement for human life as it is: brain cells with no or few mitochondria exercising muscles A constant source of GLUCOSE is an absolute requirement for human life as it is: 1- Preferred energy of the brain 2- Required energy source for cells with no or few mitochondria (as RBCs) 3- Essential source of energy for exercising muscles (substrate for anerobic glycolysis) Critical importance of glucose

Glucose transport into cells 1- Na+-independent facilitated diffusion transport: with concentration Transport occurs with concentration gradient No No require for energy (i.e. ATP) It is conducted by a group of at least 14 glucose transporters GLUT-1 to 14 (GLUT-1 to 14)

GLUT-1 RBCsBrain GLUT-1 is abundant in RBCs & Brain GLUT-2liverkidney  -cells of the pancreas GLUT-2 is found in liver, kidney &  -cells of the pancreas Function in both directions (from blood to cells & from cells to blood) GLUT-3neurons GLUT-3 primary glucose transporter in neurons GLUT-4 adipose tissue skeletal muscles GLUT-4 is abundant in adipose tissue & skeletal muscles Number is increased by insulin GLUT-5fructose GLUT-5 is the primary transporter of fructose GLUT-7gluconeogenic tissue GLUT-7 is expressed in gluconeogenic tissue (as the liver) mediates glucose flux across ER membrane Glucose transport into cells Glucose transport into cells (cont.)

Glucose transporters (GLUT)

2- Na + -monosaccharide cotransporter system against a concentration gradient Glucose is transported against a concentration gradient from low glucose concentrations outside the cell to higher concentrations within the cell Energy-requiring process movement of glucose is coupled to the concentration gradient of Na+, It is a carrier-mediated process in which the movement of glucose is coupled to the concentration gradient of Na+, which is transported into the cell at the same time epithelial cells of the intestine This type of transport occurs in the epithelial cells of the intestine renal tubules & renal tubules Glucose transport into cells Glucose transport into cells (cont.)

GLUCOSE TRANSPORT & INSULIN

Sources of Glucose to human Body Glucose can be obtained from three primary sources: Carbohydrate in Diet: Carbohydrates are sources for glucose of the body after meals. Excess glucose is stored in the form of glycogen in liver & skeletal muscles. Glycogen degradation (Glycogenlysis): Glycogen (synthesized from glucose molecules) is stored in liver & skeletal muscles. liver glycogen In cases of fasting, liver glycogen is degraded to yield glucose for blood. muscle glycogen In cases of muscular exercise, muscle glycogen is degraded to secure glucose for muscles as a source of energy. Gluconeogenesis (Glucose Synthesis): It is the synthesis of glucose from non carbohydrate sources (as some amino acids) It occurs in prolonged fasting

Sources of glucose of carbohydrate diet Free Monosaccharides 1- Free Monosaccharides: glucose & fructose mainly glucose & fructose Fructose is converted into glucose in liver Disaccharides 2- Disaccharides: Sucrose - Sucrose (glucose & fructose) - Lactose - Lactose (glucose & galactose) - Maltose - Maltose (glucose & glucose) They are digested into monosaccharides (glucose, fructose & galactose) in the intestine. Fructose & galactose are converted into glucose in the liver Polysaccharides 3- Polysaccharides : Starch - Starch (plant source e.g. rice, potato, flour) Glycogen - Glycogen (animal source) They are digested into glucose in the GIT

Metabolic pathways of glucose GLUCOSE Glycogenesis Gluconeogenesis Hexosesfructose & galactose Glycogenolysis Glycolysis Krebs cycle HMP/PPP Hexoses fructose & galactose PRODUCTIONUtilization

Pathways of glucose utilization 1- Catabolic pathways: For providing energy (ATP): 1- For providing energy (ATP): Glycolysis lactate Anaerobic Glycolysis: end product is lactate pyruvate Aerobic Glycolysis: end product is pyruvate For providing synthetic products 2- For providing synthetic products: Hexose monophosphate pathway NADPHRibose 5-Phosphate (Produces NADPH & Ribose 5-Phosphate) 2- Synthetic pathways: Glycogen synthesis

GLUCOSE GLUCOSE Pyruvate Acetyl CoA Citric Acid Cycle NADH & FADH2 Electron transport chain (flow of electrons) ATP Formation of ATP (oxidative phosphorylation) Utilizationof Glucose Glucose HEXOSE MONOPHOSPHATE PATHWAY Ribose-5 Phosphate Glycogen GLYCOGENSYNTHESIS GLYCOLYSIS NADPH Lactate Lactate Oxygen & Mitochondria No Oxygen No Mitochondria OR BOTH