Lecture Notes for Chapter 19 Regulation of Mammalian Fuel Metabolism

1. Essential Biochemistry Third Edition Charlotte W. Pratt | Kathleen Cornely Lecture Notes for Chapter 19 Regulation of Mammalian Fuel Metabolism

2. KEY CONCEPTS: Section 19-1 • Various organs are specialized for fuel storage, mobilization, and other functions. • Metabolites travel between tissues in interorgan metabolic pathways.

3. Cellular Locations of Major Metabolic Pathways

4. Organs are specialized for different functions.

5. Metabolites travel between organs. • Cori cycle • Transport of lactate from muscle to liver • Glucose-alanine cycle • Pyruvate is produced by muscle glycolysis. • Pyruvate is transaminated to make alanine. • Alanine is transported from the muscle to the liver.

6. The Cori Cycle

7. The Glucose-Alanine Cycle

8. KEY CONCEPTS: Section 19-2 • Pancreatic cells release insulin in response to increases in circulating glucose. • Insulin stimulates the uptake of glucose and the storage of metabolic fuels. • Glucagon and epinephrine promote glycogenolysis and lipolysis. • Hormones produced by adipose tissue and digestive organs regulate appetite and fuel metabolism. • AMP-dependent protein kinase activates ATP-producing pathways and inhibits ATP-consuming pathways.

9. Insulin (shown), glucagon, and catecholamines are important hormones for fuel metabolism.

10. Pancreatic islets produce insulin and glucagon.

11. Insulin is released in response to glucose. • At physiological conditions, hexokinase is saturated. • Glucose phosphorylation by glucokinase varies with glucose concentration. • Glucokinase appears to be a glucose sensor, triggering insulin release.

12. Insulin promotes fuel use and storage.

13. Impact of Insulin on GLUT4 • Insulin triggers vesicle fusion to the plasma membrane. • Glucose transporter proteins (GLUT4) are presented to the cell surface.

14. Insulin signaling also impacts glycogen-metabolizing enzymes.

15. Glucagon and epinephrine trigger fuel metabolism. Structure of Glucagon • Glucagon is synthesized and released when blood glucose concentrations drop below 5 mM.

16. Glucagon and epinephrine trigger fuel metabolism.

17. AMP-dependent protein kinase acts as a fuel sensor. Structure of AMPK

18. KEY CONCEPTS: Section 19-3 • The body breaks down glycogen, fats, and proteins to generate glucose, fatty acids, and ketone bodies during starvation. • Obesity appears to result from metabolic, environmental, and genetic factors. • In diabetes, either a lack of insulin or the inability to respond to it leads to hyperglycemia. • The metabolic syndrome is characterized by obesity and insulin resistance.

19. The body generates glucose and ketone bodies during starvation.

20. Obesity has multiple causes. • Obesity is impacted by several factors. • Diet • Metabolism • Environmental • Genetic • The hormone leptin may establish the human body’s set point weight. • Distinctions in brown vs. white adipose tissue.

21. Diabetes is characterized by hyperglycemia. • Diabetics excrete large amounts of sugar in their urine. • Type 1 diabetes is an autoimmune disease. • In Type 2 diabetes, the body does not respond to insulin.

22. Excess glucose is converted to sorbitol.

23. Accumulation of sorbitol in the lens leads to cataract formation.

24. Antidiabetic drugs work by different mechanisms.

25. The metabolic syndrome links diabetes and obesity. • Metabolic syndrome can be characterized by high visceral fat. • High levels of dietary fats can lead to: • Fat accumulation in adipose tissue • Impairment of GLUT4 translocation • Impediment of glucose uptake • Increased gluconeogenesis • Weight loss improves symptoms of metabolic syndrome.