BOK121 Lecture two.pdf

BOK 121 Carbohydrates metabolism (II) Dr. M Gamede [email protected] BMS building: Room No.7:13 Learning objectives ✓ Understand the structure and function of carbohydrates ✓ the route of ingestion, metabolism, and fate of carbohydrates ✓ Know the different glucose transport proteins a...

BOK 121 Carbohydrates metabolism (II) Dr. M Gamede [email protected] BMS building: Room No.7:13 Learning objectives ✓ Understand the structure and function of carbohydrates ✓ the route of ingestion, metabolism, and fate of carbohydrates ✓ Know the different glucose transport proteins and the glucose requirement of the body What are carbohydrates ?? ✓ Carbohydrate (Saccharide): biological molecules made of different lengths of joined carbon atoms, attached to hydrogen and oxygen, in a ratio of roughly one carbon atom to one water molecule ✓ Classified as mono-, di-, or polysaccharides ✓ Carbon number and attached groups determine it characterization Structures of carbohydrates ✓ The structures of carbohydrates can occur in two forms, Ketones and aldehydes or Enantiomers ✓ Ketoses or ketones: ketone group attached to carbon chain, ✓ Ketoses are monosaccharides that contain a ketone group (C=O) ✓ Aldoses or aldehydes: aldehydes group attached to carbon chain ✓ Aldoses are monosaccharides that contain an aldehyde group (-CHO) at the end of the carbon chain Structures of carbohydrates  Structures of carbohydrates ✓ The hydroxyl group (-OH) on the C1 of one glucose molecule reacts with the hydroxyl group on the C6 of another glucose molecule. ✓ This reaction results in the formation of a covalent bond and the release of a water molecule (a condensation reaction) Structures of carbohydrates Complex carbohydrates Digestion of carbohydrates Digestion in the intestine Absorption of carbohydrates ✓ Only monosaccharides are absorbed ✓ Galactose, glucose and fructose ✓ Need to move from intestinal lumen into the blood stream ✓ Transported through the intestine epithelium Membrane transport ✓ Molecules are carried across the membrane ✓ Channels, carriers, pump ✓ Transport is mediated through chemiosmotic cycles Membrane transport ✓ Primary action of a pump generates a ion gradient ✓ Potential energy is used to carry other molecules against their gradient across membrane Glucose absorption ✓ Sodium glucose linked transporter -symporter ✓ Primary- Na/K ATPase with K channel ✓ GLUT2 uniporter Fructose Absorption ✓ Fructose moves passively through cell using the GLUT5 uniporter at the apical side and the GLUT2 uniporter at the basal side Glucose transporters (GLUT) ✓ Insulin-dependent glucose uptake ✓ Insulin-independent glucose uptake ✓ Sensing ✓ Storage Fate of Glucose Glucose regulation ✓ Blood glucose levels trigger pancreatic cells – homeostasis ✓ High [] – beta cells release insulin ✓ Low [] – alpha cells release glucagon ✓ Insulin acts to activate the transport of glucose into cell via the GLUT4 transporter Insulin secretion ✓ When blood glucose levels rise (e.g., after a meal), glucose enters beta cells via the GLUT2 transporter ✓ The closure of KATPATP channels results in membrane depolarisation. ✓ The influx of calcium ions triggers the fusion of insulin-containing granules with the plasma membrane and the release of insulin into the bloodstream Insulin action ✓ Binds to Insulin Receptor ✓ Activation of signalling pathway ✓ Transports GLUT4 from vesicles in cytoplasm to plasma membrane Glucose cellular metabolism Hepatic glucose handling ✓ The liver is the endocrine organ that produces hepatokines (insulin-like growth factor (somatomedin), angiotensinogen, thrombopoietin) ✓ Excess glucose stored as glycogen ✓ In starvation : ✓ Glucose can be generated through glycogenolysis or gluconeogenesis in the liver ✓ The liver also synthesis ketones that can be used for energy (ketogenesis and ketoacidosis) Glycogen synthesis ✓ For maintaining blood glucose levels and providing energy during fasting or increased energy demands ✓ Conversion of glucose to glycogen through a series of enzymatic steps: ✓ Glucose phosphorylation ✓ Isomerization ✓ Formation of UDP-glucose ✓ Regulated by hormonal signals (primarily insulin and glucagon) Gluconeogenesis and glycogenolysis ✓ Glucose generation from non- carbohydrate sources ✓ Glucogenic amino acids, glycerol, lactate ✓ Low [glucose] triggers glycogen catabolism ✓ Process happens in muscle and liver Ketogenesis ✓ Formation of ketone bodies from acetyl CoA(glucogenic amino acids, fatty acids and pyruvates) in the liver ✓ Insulin and Glucagon ✓ High levels of fatty acids and low levels of glucose favour ketone body production Brain glucose handling ✓ Glucose is transported into brain cells by GLUT3 ✓ Energy usage: 160 g (420 kcal) per day ✓ Needs energy to run Na/K pumps which use ATP Muscular glucose handling ✓ Muscles need to produce ATP at fast rate ✓ Store glycogen (1200 kcal) converted to glucose-6-phosphate and glucose used in contracting muscle ✓ Resting muscle use fatty acids as fuel ✓ Cardiac muscle, no glycogen, uses fatty acids Energy production in muscle ✓ Resting condition ✓ Fatty acid metabolism ✓ Early energy expenditure ✓ Phosphocreatine delivers phosphate to ADP to generate ATP using creatine kinase enzyme Intermediate energy expenditure ✓ Anaerobic metabolism ✓ Glycolysis, lactate production ✓ Faster, less efficient ✓ Lactate to liver for gluconeogenesis Cori cycle or lactate cycle ✓ Lactate produced in muscle is transported to liver ✓ In liver it is metabolised to c pyruvate, gluconeogenesis and glucose moves back to the muscle Long-term energy expenditure ✓ Aerobic metabolism ✓ Slower rate, higher ATP ✓ Long-term exercise ✓ Carbohydrates: Stored as glycogen in the liver and muscles. ✓ Fats: Stored as triglycerides in adipose tissue. ✓ Proteins: Amino acids are deaminated and converted into intermediates that enter the citric acid cycle. Thank You