Metabolism of Carbohydrates Glycogen Metabolism

Types of hormones Glucagon: produced by the pancreas when blood glucose is low Insulin: produced by the pancreas when blood glucose is high Epinephrin: released by the adrenal glands, high exercise Glucocorticoids (cortisol) – steroid hormone released by the adrenal glands The types of hormones that we will talk about today; keep in mind the condition sunder which they are released throughout the lecture; things will make more sense that way.

Control of glucose uptake Glucose needs specific transporters to enter the cells In Brain, liver and RBC NOT Insulin dependent In Muscle and adipose cells Insulin dependent 3. Once taken inside the cell, the first step is Phosphorylation (hexokinase or glucokinase) Glucose needs specific transporters to be taken up inside the cell, once you have high glucose levels, the cells sense this and they send more transporters to the membrane to take it up. Different organs have different sensitivities due to the presence of the sensor (transporter) inside the cells. Once inside the cell, glucose is phosphorylated that makes it stuck inside the cell now.

Gluconeogenesis - overview Metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, pyruvate, glycerol, and glucogenic amino acids. To supply Brain, RBC, exercising muscle, etc. It takes place in the liver and to a lesser extent in the cortex of the kidneys. Occurs during periods of fasting, starvation or intense exercise Sum reaction: 2 pyruvate + 4 ATP + 2 GTP + 2NADH + 6H2O  glucose +2 NAD+ + 4 ADP + 2 GDP + 6 Pi + 4 H+

Glycolysis and Gluconeogenesis – regulation – hormonal Liver Glucagon,epinephrin (cAMP) Glycogen Glucose-6-phosphate Pyruvate Glucose Muscle Epinephrin (cAMP) Glucose Glycogen Glucose-6-phosphate Pyruvate Glycogenolysis ON Glycogenolysis ON Gluconeogenesis Very little occurs in muscle Does NOT occur In muscle ! Glycolysis OFF Glycolysis ON Gluconeogenesis ON the signal for the liver to make more blood glucose is GLUGAGON: activates glycogen breakdown and gluconeogenesis. Glycolysis needs to be inhibited cuz you don't want to activate glucose breakdown and synthesis at the same time. In Muscle, no receptor for glucagon, epinephrine results in an increase in cAMP designed to increase ATP production. So turn ON glycogen breakdown, and logically would turn ON glycolysis to generate more ATP During stravation, Cortisol, promotes gluconeogenesis, protein breakdown in muscle, supplies amino acids to the liver.

Glycogen Metabolism - overview - Functions as energy storage in animal cells: In liver and muscle Skeletal muscle - ~400g glycogen (1-2% weight) Liver - ~100g glycogen (6-8% weight) Glycogen exists in cytoplasmic granules that contain enzymes for its synthesis and breakdown Liver glycogen  during well-fed state,  during fasting. Muscle glycogen only moderately depleted during prolonged fasting. Glycogen granules in liver cells

Glycogen Metabolism - synthesis glucose-6-P glucose HK or GK glucose-1-P phosphoglucomutase UTP UDP-glucose + PPi (UDP-l) UDP-glucose pyrophosphorylase -O-l-l-l-l UDP -1,4 bonds { glycogen synthase -O-l-l-l-l-l-l-l-l-l-l -l-l-l-l Transferase -1,6 bond

Glycogen Metabolism – breakdown (glycogenolysis) (glucose)n l-l-l-l-l-l-l-l-l~ Glucose-1-P + l-l-l-l-l-l-l-l~ Pi (glucose)n-1 glycogen phosphorylase phosphoglucomutase Glucose-6-P Note: free glucose is released from each -1,6 linked residue degradation of branch points requires 2 further enzymes

Glycogen Metabolism – regulation Liver ( maintains BGL ): Well fed state: Glycogen synthesis During fasting: Glycogen breakdown Skeletal muscle During exercise: During rest: Regulation is complex - controlled by enzyme activation and hormones

Insulin Produced in pancreas -  Blood glucose level Blood glucose normal range 3.3 - 7 mM balance maintained between: glucose utilisation - glycolysis, synthesis of glycogen and fatty acids b) glucose production - gluconeogenesis and glycogen breakdown. All of the above pathways are subject to hormonal control.

Insulin When blood glucose  - insulin is secreted -  rate of glucose uptake in liver and peripheral tissues  plasma glucose  - when this falls below a critical value - insulin secretion  - glucagon secreted, therefore the insulin/glucagon is critical in maintenance of blood glucose level. Diabetes is characterised by abnormally  blood glucose level and intolerance to ingested glucose.

Insulin and diabetes Type I – Juvenile onset – insulin-dependent: autoimmune attack on insulin producing cells in the pancreas, so insulin production is deficient. Responds to insulin injection. Type II – non-insulin dependent: insulin levels may be normal, but the cells are insensitive due to a down regulation of the insulin receptors. Usually onset occurs after age 35, frequently associated with obesity.