OVERVIEW OF METABOLISM

1. OVERVIEW OF METABOLISM Medical Biochemistry, Lecture 30

2. Lecture 30, Outline • Review metabolic fates of carbohydrates, amino acids and lipids/fats • Discuss ATP and its role in metabolism • Harper’s Ch 17 primary source material Chapters 15 and 16, supplemental and review sources

3. Two-Way Street: Medicine and Biochemistry

4. Metabolic Homeostasis

5. Types of Metabolic Pathways Catabolic Pathways produce free energy compounds Anabolic Pathways utilize these compounds Figure 17-1

6. Overview of Dietary Catabolism Figure 17-2

7. Carbohydrate Metabolism: Fate of Glucose 1. Glycolysis (enzymatic breakdown and interconversions of carbon atoms derived from glucose) ultimately yields ATP and CO2 2. Converted to glycogen, a storage polymer of potential metabolic energy 3. Generates reducing equivalents (H+) for fatty acid synthesis and ribose for nucleotide synthesis (via the pentose phosphate pathway) 4. Triose phosphate can be metabolized to the glycerol backbone of triacylglycerols (fat) 5. Pyruvate (and other metabolites) can provide the carbon skeletons for some amino acids; acetyl CoA necessary for long chain fatty acid and cholesterol synthesis

8. Carbohydrate Metabolism Figure 17-3

9. Lipid Metabolism: Caloric Storage and Oxidation 1. Esterified and stored as triglycerides 2. b-Oxidation of fatty acids generates energy and leads to acetyl-CoA (which enters the citric acid cycle)  3. Carbon source for cholesterol and other steroids 4. Can form ketone bodies in the liver (alternative water-soluble energy sources during starvation conditions)

10. Lipid Metabolism Figure 17-4

11. Amino Acid Metabolism: Essential and Non-Essential 1. All amino acids can be provided by diet, but some must be specifically supplied since we do not possess biosynthetic enzymes to make them (essential amino acids) 2. Non-essential amino acids can be interconverted to other metabolic products via transamination and deamination reactions.

12. Amino Acid Metabolism Figure 17-5

13. Hepatic Portal Vein and Metabolite Absorption • Water-soluble metabolites like glucose (resulting from digestion of dietary carbohydrates) and amino acids (from protein digestion) are directed from the small intestine to the liver via the hepatic portal vein.

14. Transport of Carbohydrate and Amino Acid Metabolites Figure 17-6

15. Transport of Lipid Metabolites Figure 17-7

16. Overview of Metabolic Pathways in a Liver Cell Figure 17-8

18. Mechanisms of Metabolic Enzyme Control: 1. Alteration of membrane permeability 2. Conversion of inactive to active enzyme (by phosphorylation,activators, proteases) 3. Alter rate of translation 4. Induce new mRNA 5. Repress mRNA Steps 1 and 2 are rapid effector mechanisms; 3,4,5 are slower Figure 17-9

19. Adenosine Triphosphate - ATP

21. High Energy Bond Use in Cells 1. Glucose conversion to intermediates with high energy phosphates 2. ATP generated from oxidative phosphorylation 3. End-product of many pathways, Acetyl-CoA, contains a high-energy thioester 4. Transfer of phosphate to make other compounds 5. Energy of hydrolysis of ATP activates membrane transport processes 6. ATP hydrolysis energy converted to movement or force

22. Electron Accepting Co-Enzymes FAD (flavin adenine dinucleotide) NAD (nicotinamide adenine dinucleotide)

23. Mitochondrial Fuel Metabolism