1 CLINICAL CHEMISTRY (MLT 301) CARBOHYDRATE LECTURE ONE Dr. Essam H. Jiffri
2 IntroductionCarbohydrates 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 thecarbohydrate moieties of glycoproteins
3 IntroductionMan can synthesize some carbohydrate from substrates such as:- Glycerol and,- Amino acids but most is derived from plant sources
4 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)
5 Blood glucose homeostasis -THE LIVERThe liver is an important organ in blood glucose homeostasis
6 Blood glucose homeostasis -THE LIVERAfter 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, andThe activity of enzymes.
7 Blood glucose homeostasis -THE LIVERIn 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.
8 Blood glucose homeostasis Glycogenolysis- The process by which glucose is released from the liver (phosphorylase the keyregulatory enzyme )
9 Blood glucose homeostasis Glycogenolysis-In well-fed individuals hepatic glycogen stores can account for up to 10% of organweight.-It forms a buffer which maintains blood glucose levels between meals.
10 Blood glucose homeostasis Gluconeogenesis- Other compounds are also converted to glucose in the liver
11 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 )
13 Blood glucose homeostasis Hormonal regulationcarbohydrate-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.
14 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
15 Blood glucose homeostasis Insulin-Insulin is an anabolic hormone whichstimulates:- glucose uptake by muscle and adipose tissue, and increases:protein synthesis,glycogen synthesislipogenesis.
16 Blood glucose homeostasis Glucagon-Glucagon is synthesized in the A (or α) cells of the pancreas.-Inhibited by glucose and insulin-Glucagon stimulates:glycogenolysis andgluconeogenesis (raising blood glucose concentrations).
17 Blood glucose homeostasis Growth Hormone-Growth hormone secretion is stimulated by hypoglycaemia-Actions include:increased hepatic glucose production, andincreased lipolysis and raising plasma NEFA levels.
18 Blood glucose homeostasis Adrenaline-Hypoglycaemia is a potent stimulus for adrenaline secretion.Inhibits insulin secretionstimulates adipose tissue lipolysis,increasing NEF A production
20 -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
21 -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 :acetoneacetoacetate, andβ-hydroxybutyrate,
22 NEFA from adipose tissue is controlled by: INTERRELATION OF GLUCOSE, NONESTERIFIED FATTY ACID AND KETONE BODY METABOLISMNEFA 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.
23 -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