Carbohydrates Part 1 Lecture 10

Introduction Organisms rely on the oxidation of complex organic compounds to obtain energy Three general types of such compounds are: Carbohydrates (CHO) Amino acids And lipids CHO are the primary source of energy for brain, erythrocytes and retinal cells Stored primarily in liver & muscle as glycogen

Carbohydrates: CHO Compounds containing C, H, O General formula (CH2O)n All CHO contain C=O and –OH functional groups There are some derivatives of this formula, carbohydrate derivatives can be formed addition of other chemical groups (phosphates, amines…) Classification of CHO is based on four different properties: The size of the base carbon chain The location of the CO functional group The number of sugar units The stereochemistry of the compound

Glucose Metabolism Glucose is a primary source of energy. Various tissues and muscles throughout the body depend on glucose from the surrounding extracellular fluid for energy. Nervous tissue cannot concentrate or store CHO, critical to maintain steady supply If glucose levels fall below certain levels the nervous tissue lose its primary energy source and is incapable of maintaining normal function.

Fate of glucose CHO is digested (starch and glycogen). Amylase digest the nonabsorbable forms of CHO to dextrin and disaccharide which are hydrolyzed to monosaccharide. Maltase is an enzyme released by intestinal mucosa that hydrolze maltose to two glucose units Sucrase hydrolyze sucrose to glucose & fructose Lactase: hydrolyze lactose to glucose & galatose.

Fate of glucose Disaccharides are converted into monosaccharide – absorbed by the gut transported to the liver by the hepatic portal venous blood supply. Glucose is the only CHO to be directly used for energy or stored as glycogen. Others (galactose & fructose) have to be converted to glucose before they can be used

Lactose intolerance Lactose intolerance: due to a deficiency of lactase enzyme on or in the intestinal lumens, which is needed to metabolize lactose. Results in an accumulation of lactose in the intestine as waste lactic acid- causing the stomach upset and discomfort. Lactose intolerance is the inability to metabolize lactose, a sugar found in milk and other dairy products, because the required enzyme lactase is absent in the intestinal system or its availability is lowered.

Fate of glucose After glucose enters the cell it can go into one of three metabolic pathways based on availability of substrate and nutritional status of cell. Ultimate goal is to convert glucose to CO2 and H2O. During this process the cell obtains the high-energy molecule (ATP) from (ADP).

Glucose metabolism 1st step in all pathways Glucose is converted to glucose -6 phosphate using ATP- catalyzed by hexokinase. Glucose-6- phosphate enters the pathways: Embden-Meyerhof pathway Hexose Monophosphate shunt Glucogenesis (storage of glucose as glycogen) glucose is broken down into two, three-carbon molecules of pyruvic acid that can enter the tricarboxylic acid cycle (TCA cycle) on conversion to acetyl-coenzyme A Pentose phosphate PathwayThe principal functions of the pathway are the production of deoxyribose and ribose sugars for nucleic-acid synthesis; the generation of reducing power in the form of NADPH for fatty-acid and/or steroid synthesis;

Glucose metabolism Embden-Meyerhof pathway Hexose Monophosphate shunt Glucose is broken down into two, three-carbon molecules of pyruvic acid that can enter the tricarboxylic acid cycle (TCA cycle) on conversion to acetyl-coenzyme A (acetyl- CoA). Hexose Monophosphate shunt The principal functions of the pathway are the production of: Deoxyribose and ribose sugars for nucleic-acid synthesis; The generation of reducing power in the form of NADPH for fatty-acid and/or steroid synthesis;

Pathways in glucose metabolism Major energy pathways involved either directly or indirectly with glucose metabolism Glycolysis Breakdown of glucose for energy production Glycogenesis Excess glucose is converted and stored as glycogen High concentrations of glycogen in liver and skeletal muscle Glycogen is a quickly accessible storage form of glucose Glycogenolysis Breakdown of glycogen into glucose Glycogenolysis occurs when plasma glucose is decreased Occurs quickly if additional glucose is needed

Pathways in glucose metabolism Gluconeogenesis Conversion of non-carbohydrate carbon substrates to glucose Gluconeogenesis takes place mainly in the liver Lipogenesis Conversion of carbohydrates into fatty acids Fat is another energy storage form, but not as quickly accessible as glycogen Lipolysis Decomposition of fat

Regulation of Carbohydrate Metabolism The liver, pancreas, and other endocrine glands are all involved in controlling the blood glucose concentrations within a narrow range During a brief fast, glucose is supplied to the ECF from the liver through glycogenolysis. When the fasting period is longer than 1 day, glucose is synthesized from other sources through gluconeogenesis. Control of blood glucose is under two major hormones: insulin and glucagon, both produced by the pancreas

Regulation of Carbohydrate Metabolism Other hormones also exert some control over blood glucose concentrations As needed hormones regulate release of glucose. Hormones work together to meet 3 requirements: Steady supply of glucose. Store excess glucose Use stored glucose as needed

Insulin Primary hormone responsible for the entry of glucose into the cell. Synthesized in the beta cells of islets of langerhans in the pancreas. Insulin release causes an increase movement of glucose into the cells and increase glucose metabolism The only hormone that decreases glucose levels and is referred to as a hypoglycemic agent.

Glucagon Peptide hormone that is synthesized by the alpha cells of the islets cells of the pancreas Released during stress and fasting states. Released in response to decreased body glucose. Main function is to: increase hepatic glycogenolysis, and increase gluconeogenesis. Hyperglycemic agent

High blood Sugar High blood Sugar Low blood Sugar

Action of Hormones Glucose  Glycogen Glucose  Pyruvate  Acetyl-CoA

Epinephrine (adrenaline) Hormone produced by the adrenal gland Increases plasma glucose by: inhibiting insulin secretion, increasing glycogenolysis and promotes lipolysis. Release during times of stress

Glucocorticoids Primarily Cortisol is released when stimulated by adrenocorticotropic hormone (ACTH). Cortisol increases plasma glucose by: Increasing gluconeogenesis, Inhibition of glucose uptake in muscle and adipose tissue and lipolysis. Adrenocorticotropic hormone =ACTH

Thyroxine The thyroid gland releases thyroxine. Increases glucose levels by: increasing glycogenolysis, gluconeogenesis And intestinal absorption of glucose.

Somatostatin Produced by the delta cells of the lslets of langerhans of the pancreas. The inhibition of insulin, glycagon Therefore only minor overall effect

Glucose uptake Glycolysis Gluconeogenesis Glycogenolysis Lipogenesis Glucose uptake Glucose uptake Glycolysis

Hyperglycemia Increase in plasma glucose levels In healthy persons during a hyperglycemia state, insulin is secreted by the beta cells of the pancreatic islets of langerhans. Insulin enhances membrane permeability to cells in the liver, muscle, and adipose tissue. Hyperglycemia is caused by an imbalance of hormones.

Diabetes Mellitus Metabolic diseases characterized by hyperglycemia resulting from defect in insulin secretion, insulin action or both. Two major types: (in 1979) Type I, (insulin dependent) and Type 2, (non insulin dependent) 1995: further categories by WHO: Type 1 diabetes, type 2 diabetes, other specific types and gestational diabetes mellitus.

Type 1 diabetes Due to cellular-mediated autoimmune destruction of the β cells of the pancreas, causing an absolute deficiency of insulin secretion Or idiopathic type 1 diabetes that has no known etiology Commonly occurs in children (juvenile diabetes) Constitutes only 10% to 20% of all cases of diabetes Genetics play a minimal role, can be due to exposure to environmental substances or viruses. Treatment: insulin

Characteristics of T1DM Abrupt onset, Insulin dependence, and ketosis tendency. One or more of the following markers are found in 85% to 90% of individuals with fasting hyperglycemia: Islet cell autoantibodies, Insulin autoantibodies, Glutamic acid decarboxylase autoantibodies

The concentration of the excreted molecules determines the urine's specific gravity. In adult humans, normal specific gravity values range from 1.003 to 1.030. Osmole: the number of moles of solute that contribute to the osmotic pressure of a solution

Type 2 diabetes mellitus Due to insulin resistance and relative insulin deficiency. Type 2 constitutes the majority of the diabetes cases Most patients in this type are obese or have an increased percentage of body fat distribution in the abdominal region often goes undiagnosed for many years and is associated with a strong genetic predisposition

Characteristics of T2DM Adult onset of the disease Ketoacidosis seldom occurring. These patients are more likely to go into a hyperosmolar nonketonic states (hyperosmolar coma) Patients are at an increased risk of developing macrovascular and microvascular complications. retinopathy, nephropathy, and neuropathy (microvascular) and ischemic heart disease, peripheral vascular disease, and cerebrovascular disease (macrovascular)

Other specific types Secondary conditions, genetic defect in beta cell function or insulin action, pancreatic disease, disease of endocrine origin, drug or chemical induced. Characteristics of the disease depends on the primary disorder.

Gestational diabetes mellitus Glucose intolerance that is induced by pregnancy Caused by metabolic and hormonal changes related to the pregnancy. Glucose tolerance usually returns to normal after delivery. An increased risk for development of diabetes in later years