1. BIOC 460 - DR. TISCHLER LECTURE 21 METABOLISM: BASIC CONCEPTS

2. 1.Identify the three major forms in which energy is stored and the four primary circulating fuels. 2.Distinguish between  G and  G , and explain the relationship between mass action effect and  G. 3.Define high-energy phosphate transfer potential, and explain its significance in terms of the formation of ATP via substrate-level phosphorylation. 4.Define the absorptive (well-fed), postabsorptive (fasting), starvation (gluconeogenic) and prolonged starvation nutritional states and identify the primary sources of glucose in each of these. OBJECTIVES

3. Catabolism: breakdown of fuels – used to produce energy Anabolism: synthesis and storage of fuels Most cells use oxidative metabolism (varying degrees) Red blood cells lack mitochondria = entirely anaerobic ATP: most common direct energy source GENERAL INFORMATION ABOUT METABOLISM

4. OVERVIEW OF METABOLIC PATHWAYS AND SYSTEMS OF ENERGY METABOLISM GLYCOGEN PROTEIN TRIACYLGLYCEROLS Pyruvate Nucleic Acids Ribose-5-P Acetyl-CoA Amino Acids Urea Glucose-6-P Glucose Lactate Ketone Bodies Free Fatty Acids ATP Figure 1. Energy systems

5. PHYSIOLOGICAL FREE ENERGY  G =  G  + 2.3 log [products/reactants]  G = actual free energy difference of reaction in cell; must be negative for reaction to proceed  G  = point of reference "mass action effect" change  G by altering ratio of products/substrates  product and/or  reactant lowers  G reaction proceeds better towards product

6. * P-O-P-O-P- O O-O- O O-O- OCH 2 O OH Adenine O O-O- O -    ATP Kcal -7.3-6.6 P * N-C NH O O-O- O-O- N CH 3 CH 2 COO - PHOSPHOCREATINE -10.3 Kcal O O-O- O-O- O O-O- O - PC O CH OH CH 2 PO O O-O- O-O- PO 1,3-bisPHOSPHOGLYCERATE -10.1 C CH 2 COO - PHOSPHOENOLPYRUVATE -14.8 O (TWO HIGH ENERGY INTERMEDIATES OF THE GLYCOLYTIC PATHWAY) * * Figure 2. Structures of important compounds having high-energy phosphate bonds. ATP formed by substrate-level phosphorylation CPK

7. GLYCOGEN GLUCOSE LACTATE Glucose-6-P Pyruvate SUMMARY OF CARBOHYDRATE PATHWAYS Glycogenolysis Glycogenesis Glycolysis Gluconeogenesis PPP NADPH formation Nucleic acid synthesis Acetyl CoA CO 2 Citric Acid Cycle anaerobic metabolism aerobic metabolism PPP = pentose phosphate pathway Figure 3. Summary of carbohydrate pathways. Pyruvate metabolism to acetyl CoA and carbon dioxide is irreversible.

8. Table 1. Summary of Nutritional States Nutritional State Description Absorptive period within no more than 4 hours after the last meal commenced during which food is digested and absorbed; also called well-fed state Post- absorptive period after food is completely digested and absorbed up until 18 to 24 hours afterwards; also referred to as a fasting state Starvation period of time from about 24 hours after the last meal and onwards until refeeding or death; early starvation is approximately the first 5 days Prolonged starvation period of time one week and longer after food deprivation

9. BLOOD GLUCOSE HOMEOSTASIS maintenance of blood glucose concentration brain depends on glucose; >50% of total prolonged starvation has <25% decline in glucose hyperglycemia – too little insulin hypoglycemia – too little intake or too much insulin

10. Table 2. Primary sources and fates of glucose, and the major fuel for the brain in each phase Nutritional status Absorptive (Well-fed) Post- absorptive (Fasting) Early Starvation Prolonged Starvation Sources of Blood Glucose Diet Liver glycogen Liver gluconeo- genesis Liver gluconeo- genesis Tissues Using Glucose (fates) All Primarily brain and red blood cells Brain and red blood cells Red blood cells only Primary Brain Fuel Glucose Ketone bodies