CLINICAL CHEMISTRY (MLT 301) CARBOHYDRATE LECTURE ONE Dr. Essam H. Jiffri

Introduction Carbohydrates are distributed widely in the body, and have: - Metabolic functions - Glucose (the principal form and the major fuel for cellular metabolism) - Structural functions: - the precursor of other sugars, such as ribose which is found in: nucleic acids, and of the carbohydrate moieties of glycoproteins

Introduction Man can synthesize some carbohydrate from substrates such as: - Glycerol and, - Amino acids but most is derived from plant sources

Blood glucose homeostasis Sources: Blood glucose is maintained from several sources including: - Diet - Ingested carbohydrate includes both: - Digestible form (starch or disaccharides-after digestion are absorbed as glucose, galactose or fructose) - Nondigestible forms (dietary fibre)

Blood glucose homeostasis -THE LIVER The liver is an important organ in blood glucose homeostasis

Blood glucose homeostasis -THE LIVER After feeding (stores some excess glucose as glycogen) In the fasted state (through glycogenolysis and gluconeogenesis, maintains blood levels) The hepatic uptake and output of glucose is controlled by: the concentration of key intermediates, and The activity of enzymes.

Blood glucose homeostasis -THE LIVER In hepatocytes, glucose phosphorylation is promoted by glucokinase which has a lower affinity than hexokinase. The activity of glucokinase increases with high blood glucose levels and the liver removes glucose from the portal blood after a meal. After uptake and phosphorylation, excess glucose is stored in the liver as glycogen.

Blood glucose homeostasis Glycogenolysis - The process by which glucose is released from the liver (phosphorylase the key regulatory enzyme )

Blood glucose homeostasis Glycogenolysis -In well-fed individuals hepatic glycogen stores can account for up to 10% of organ weight. -It forms a buffer which maintains blood glucose levels between meals.

Blood glucose homeostasis Gluconeogenesis - Other compounds are also converted to glucose in the liver

Blood glucose homeostasis Gluconeogenesis - lactate, glycerol and amino acids, particularly alanine, are gluconeogenic substrates. - Lactate is continually produced by partial oxidation of glucose in muscle and erythrocytes and is reconverted to glucose in the liver by the (Cori cycle )

Cori cycle Muscle (glycogen( Blood Liver Glucose Glucose-6-phosphate Lactate Lactate CO2 + H2O

Blood glucose homeostasis Hormonal regulation carbohydrate-rich meal also affects the release of several hormones: -Insulin is the major hypoglycaemic hormone -Other hormones, including glucagon, growth hormone, cortisol and adrenaline are counter-regulatory; these antagonize the effects of: insulin and have gluconeogenic effects.

Blood glucose homeostasis Insulin -Insulin is synthesized by the B (or β) cells in the islets of Langerhans of the pancreas. -Glucose stimulates insulin release

Blood glucose homeostasis Insulin -Insulin is an anabolic hormone which stimulates: - glucose uptake by muscle and adipose tissue, and increases: protein synthesis, glycogen synthesis lipogenesis.

Blood glucose homeostasis Glucagon -Glucagon is synthesized in the A (or α) cells of the pancreas. -Inhibited by glucose and insulin -Glucagon stimulates: glycogenolysis and gluconeogenesis (raising blood glucose concentrations).

Blood glucose homeostasis Growth Hormone -Growth hormone secretion is stimulated by hypoglycaemia -Actions include: increased hepatic glucose production, and increased lipolysis and raising plasma NEFA levels.

Blood glucose homeostasis Adrenaline -Hypoglycaemia is a potent stimulus for adrenaline secretion. Inhibits insulin secretion stimulates adipose tissue lipolysis, increasing NEF A production

Blood glucose homeostasis Cortisol -Cortisol stimulates: hepatic gluconeogenesis promotes adipose tissue lipolysis and NEFA release

-Alternative fuels are required during prolonged fasting or starvation INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE BODY METABOLISM -Muscle has a higher rate of fuel utilization than other organs during exercise. -The brain, kidney and intestine utilize a higher percentage of available glucose at rest. -Alternative fuels are required during prolonged fasting or starvation

-The ketone bodies derived from fatty acid metabolism in the liver : INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE BODY METABOLISM -The ketone bodies derived from fatty acid metabolism in the liver : acetone acetoacetate, and β-hydroxybutyrate,

NEFA from adipose tissue is controlled by: INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE BODY METABOLISM NEFA from adipose tissue is controlled by: the activity of hormon-sensitive lipase. Insulin inhibits this enzyme (anti-lipolytic) adrenaline, growth hormone, glucagon and cortisol are lipolytic. - Greater fluxes of NEFAs occur if carbohydrate availability is limited.

-In the liver, NEFAs are either: INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE BODY METABOLISM -NEFAs are transported in blood bound to albumin; about 30% is extracted by the liver. -In the liver, NEFAs are either: reesterified to form triglycerides or, metabolized by Beta-oxidation in mitochondria to form acetyl CoA

KEY POINTS Ketone bodies are produced from NEFA in the liver Ketone bodies are a alternative fuel for brain metabolism In the starvation many organs utilize ketones, sparing glucose