CLINICAL CHEMISTRY (MLT 301) CARBOHYDRATE LECTURE ONE

1. CLINICAL CHEMISTRY (MLT 301)CARBOHYDRATELECTURE ONE Dr. Essam H. Jiffri

2. 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

3. Introduction • Man 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 LIVER • The liver is an important organ in blood glucose homeostasis

6. 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.

7. 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.

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

9. 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.

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 )

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

13. 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.

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 which • stimulates: • - glucose uptake by muscle and adipose tissue, and increases: • protein synthesis, • glycogen synthesis • lipogenesis.

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 and • gluconeogenesis (raising blood glucose concentrations).

17. 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.

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

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

20. 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. 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,

22. 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.

23. 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

25. 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