Glycolysis: Phase 1 and 2 Phase 1: Sugar activation two ATP molecules used to activate glucose into: fructose-1,6-diphosphate Phase 2: Sugar cleavage Fructose-1,6-bisphosphate is cleaved into: two 3-carbon isomers Phase 3: Oxidation and ATP formation 3-carbon sugars are oxidized (reducing NAD+) ATP is formed by substrate-level phosphorylation

Glycolysis Figure 24.6 Glucose Key: Phase 1 Sugar activation 2 ATP Krebs cycle Electron trans- port chain and oxidative phosphorylation ATP ATP ATP Glucose Key: Phase 1 Sugar activation 2 ATP = Carbon atom 2 ADP Pi = Inorganic phosphate Fructose-1,6- bisphosphate P P Phase 2 Sugar cleavage Dihydroxyacetone phosphate Glyceraldehyde phosphate P P Pi 2 NAD+ 4 ADP 2 NADH+H+ 4 ATP Phase 3 Sugar oxidation and formation of ATP 2 Pyruvic acid 2 NADH+H+ O2 O2 2 NAD+ To Krebs cycle (aerobic pathway) 2 Lactic acid Figure 24.6

The final products of glycolysis: Glycolysis: Phase 3 The final products of glycolysis: Two pyruvic acid molecules Two NADH + H+ molecules (reduced NAD+) A net gain of two ATP molecules (4ATP- 2ATP)

Krebs Cycle: Preparatory Step Occurs inside the mitochondria in the mitochondrial matrix Fueled by: Pyruvic acid (carbohydrates) Fatty acids (lipids) Pyruvic acid is converted to acetyl CoA in three main steps: Decarboxylation Carbon is removed from pyruvic acid Carbon dioxide is released

Krebs Cycle: Preparatory Step Oxidation Hydrogen atoms are removed from pyruvic acid NAD+ accepts the H2 atoms and is reduced to NADH + H+ Formation of acetyl CoA Decarboxylation results in acetic acid formation Acetci acid combines with Co A Acetyl CoA is formed

Each molecule of glucose entering glycolysis, results in: Krebs Cycle A cycle of eight steps in which each acetic acid is decarboxylated and oxidized, generating: Three molecules of NADH + H+ One molecule of FADH2 Two molecules of CO2 One molecule of ATP Each molecule of glucose entering glycolysis, results in: Two molecules of acetyl CoA entering the Krebs cycle

Figure 24.7 Pyruvic acid from glycolysis Cytosol CO2 NAD+ CoA NADH+H+ Electron transport chain and oxidative phosphorylation Krebs cycle CO2 NAD+ CoA NADH+H+ Mitochondrion (fluid matrix) Acetyl CoA ATP ATP ATP Oxaloacetic acid Citric acid NADH+H+ (pickup molecule) CoA (initial reactant) NAD+ Malic acid Isocitric acid NAD+ Krebs cycle CO2 NADH+H+ Fumaric acid a-Ketoglutaric acid CoA CO2 FADH2 NAD+ Succinic acid Succinyl-CoA NADH+H+ FAD Key: CoA = Carbon atom GTP GDP + Pi Pi = Inorganic phosphate CoA = Coenzyme A ADP ATP Figure 24.7

Electron Transport Chain The released hydrogens from glucose oxidation: Are transported by coenzymes NADH and FADH2 Enter a chain of proteins Combine with molecular oxygen to form water Release energy Energy released is harnessed to: Attach inorganic phosphate groups (Pi) to ADP Making ATP by oxidative phosphorylation

Mechanism of Oxidative Phosphorylation hydrogens delivered to the chain are split into: Protons (H+) and electrons Protons are pumped across Inner mitochondrial membrane Electrons are shuttled from: One acceptor to the next

Mechanism of Oxidative Phosphorylation Electrons are delivered to oxygen, forming oxygen ions Oxygen ions attract H+ to form water H+ pumped to the intermembrane space Diffuses back to the matrix via ATP synthase Releases energy Energy is used to bond inorganic phosphate (Pi) to ADP producing ATP

Summary of ATP Production Figure 24.11

Glycogenesis and Glycogenolysis Formation of glycogen When glucose supplies exceed cellular need for ATP synthesis Glycogenolysis: Breakdown of glycogen In response to low blood glucose Figure 24.12

Formation of sugar from non-carbohydrate molecules Gluconeogenesis Formation of sugar from non-carbohydrate molecules Takes place mainly in the liver Protects the body, especially the brain: From damaging effects of hypoglycemia By ensuring ATP synthesis can continue

Pancraatic lipases digestion of lipids results in: Lipid Metabolism Pancraatic lipases digestion of lipids results in: Free fatty acids (FFA) Monoglycerides Glycerol FFA & monoglycerides are water insoluble They quickly associate with: Bile salts (Polar & non-polar faces) Lecithin (phospholipid) This association forms micelles

Micelles reach epithelial surface (between microvilli) Lipid Metabolism Micelles reach epithelial surface (between microvilli) Their content leave and diffuse thru plasma membrane Inside epith. cell (sER) triglycerides are resynthesized Triglycerides combine with: Lecithin, other phospholipids, cholesterol Combination is then coated with protein forming chylomicrons (H2O soluble lipoprotein) Chylomicrons (too big) leave epith. cells by exocytosis They enter lacteals (more permeable) & transported as lymph They join the venous blood thru the thoracic duct

Lipid Metabolism Triglycerides in chylomicrons are hydrolyzed to fatty acids & glycerol Hydrolysis is achieved by the enzyme lipoprotein lipase This enzyme is associated with the capillary endo- thelium of the liver & adipose tissue The resulting fatty acids & glycerol can then pass thru the capillary walls to be used by tissue cells Residual chylomicron is made into new lipoprotein by the liver cells & used in colesterol transport Only neutral fats are routinely oxidized for energy

Catabolism of fats involves two separate pathways Lipid Metabolism Catabolism of fats involves two separate pathways Glycerol pathway Fatty acids pathway Glycerol is converted to: Glyceraldehyde phosphate (GP) GP is converted into acetyl CoA Acetyl CoA enters the Krebs cycle Energy (ATP) is produced

Fatty acids undergo β-oxidation, which produces: Lipid Metabolism Fatty acids undergo β-oxidation, which produces: Two-carbon acetic acid fragments These fragments enter the Krebs cycle The resulting reduced coenzymes enter the electron transport chain Energy (ATP) is produced Short chain fatty acid from fat breakdown: Don not follow the pathway described above Simply diffuse into portal blood & be distributed

Lipid Metabolism Figure 24.13

Lipogenesis and Lipolysis Conversion of excess dietary glycerol and fatty acids into triglycerides Glucose is easily converted into fat since acetyl CoA is: An intermediate in glucose catabolism The starting molecule for fatty acid synthesis

Lipogenesis and Lipolysis The breakdown of stored fat Is essentially lipogenesis in reverse

Excess dietary protein results in: Protein Metabolism Excess dietary protein results in: Amino acids oxidation for energy Convertion of amino acids into fat for storage Amino acids must be: Deaminated prior to oxidation for energy Deaminated amino acids are converted into: Pyruvic acid, or One of the intermediate keto acids These acids are intermediates in the Krebs cycle

A brief summary of liver functions: Packages fatty acids to be stored and transported Synthesizes plasma proteins Forms nonessential amino acids Converts deamination ammonia into urea Stores glucose as glycogen Regulates blood glucose homeostasis Stores vitamins, Detoxifies substances

Is the structural basis of: Cholesterol Is the structural basis of: Bile salts Steroid hormones, and Vitamin D Transported : To and from tissues via lipoproteins

Lipoproteins are classified as: Cholesterol Lipoproteins are classified as: HDLs (Healthy cholesterol): High-density lipoproteins Have more protein content LDLs (Lethal cholesterol): Low-density lipoproteins Have a considerable cholesterol component VLDLs: Very low density lipoproteins Are mostly triglycerides

Cholesterol Figure 24.22

Lipoproteins High levels of HDL: High levels of LDL: Thought to protect against heart attack High levels of LDL: Increase the risk of heart attack

Plasma Cholesterol Levels The liver produces cholesterol: At a basal level regardless of dietary intake Via a negative feedback loop involving low serum cholesterol levels In response to saturated fatty acids (stimulate synthesis & inhibit excretion)

Regulation of Body Temperature Balance between heat production and heat loss At rest, most heat production is accounted for by: Liver, heart, brain, and endocrine organs During vigorous exercise: Heat production from skeletal muscles can increase 30–40 times

Regulation of Body Temperature Normal body temperature: Averages 37 C (98.6F) Ranges 35.8-38.2C (96-101F) Fluctuates 1C (1.8F) /24hrs (morning vs evening) Optimal enzyme activity occurs at this temperature Temperature spikes above this range: Denature proteins Depress neurons

Core and Shell Temperature Core organs (have the highest temperature) are found: Within the skull Thoracic cavity Abdominal cavity The shell (has the lowest temperature) : Essentially the skin Major agent of heat transfer between the core and shell: Blood Core temperature: Remains relatively constant Shell temperature: Fluctuates substantially (20–40C)

Mechanisms of Heat Exchange Four mechanisms: Radiation: Loss of heat in the form of infrared rays Conduction Transfer of heat by direct contact Convection Transfer of heat to the surrounding air Evaporation Heat loss due to the evaporation of water from the: Lungs Mouth mucosa Skin

Heat-Promoting Mechanisms Stimuli: Low external temperature Low temperature of circulating blood Heat-promoting centers (hypothalamus) cause: Vasoconstriction of cutaneous blood vessels Increased metabolic rate Shivering Enhanced thyroxine release

Heat-loss center is activated to cause: Heat-Loss Mechanisms Stimulus: Core temperature rises: Heat-loss center is activated to cause: Vasodilation of cutaneous blood vessels Enhanced sweating Voluntary measures to reduce body heat: Reduce activity Seek a cooler environment Wear light-colored & loose-fitting clothing