Metabolism Chapter 24 Biology 2122

Metabolism overview 1. Metabolism: – Anabolic and Catabolic Reactions 2. Cell respiration -catabolic reaction 3. Metabolic pathways 4. Cell Respiration – Digestion and absorption of nutrients – In the cell anabolic process build up lipids, proteins, glycogen – Aerobic respiration in the mitochondria will produce ATP

Important Aspects of Metabolism 1. Metabolic pathways – enzyme mediated 2. Glucose is oxidized – other compounds are reduced. 3. Coenzymes – become reduced – compounds electron and proton carriers. 4. Phosphorylation – Hydrolysis of ATP – Transfer of an inorganic phosphate from ATP

Oxidation and reduction 1. Glucose - oxidized in the cell – C 6 H 12 O 6 + 6O  6CO 2 + 6H 2 O + ATP + Heat Oxidation – gain of oxygen or loss of a hydrogen – Loss of electrons Reduction - gain of hydrogen and electrons – Cellular respiration oxygen is reduced – Any compound that receives electrons and hydrogen’s are reduced – OIL RIG Dehydrogenases – Enzymes that remove hydrogen atoms from organic compounds

Role of coenzymes 1.When hydrogen and electrons are being transferred from one compound to another, which compounds will accept them? 2. Coenzymes – Organic compounds (enzyme with a vitamin) – NAD+ (nicotinamide adenine dinucleotide) (niacin) – FAD – (flavin adenine dinucleotide) (flavin) 3. What will they do after they are reduced? – Carry hydrogen and electrons to the ‘electron transport chain’ and unload them – Final production of ATP

Phosphorylation and ATP synthesis Transfer of a phosphate group to another compound Metabolic pathways – Produce ATP Substrate-level phosphorylation Oxidative phosphorylation

ATP formation

Glycolysis In the Box: Glucose (6-C) and Oxygen Out of the Box: Pyruvic Acid (3-C)

Glycolysis 1. Sugar Activation 2. Sugar Cleavage – Fructose 1,6-bisphosphate splits into (2) 3-C compounds 3. ATP and Pyruvate formation – Final produce is (2) 3-C pyruvate Net Totals – 2 ATP; 2 NADH + H+

Preparing for the Krebs cycle 1. What happens to the 3-C pyruvate? 2. If oxygen is not available (anaerobic) – Undergo lactic acid fermentation – Only 2 ATP produce and lactic acid which causes soreness in the muscles 3. If oxygen is available (aerobic) then pyruvate is processed – In the cytosol of mitochondria pyruvate loses a C (CO 2 ) and becomes acetic acid “decarboxylation” – Coenzyme A attaches to Acetic Acid ---  2-C Acetyl CoA

Krebs cycle In the Box: Acetyl CoA Out of the Box: CO 2 FADH 2 NADH ATP

Krebs cycle 2-C acetyl CoA is picked up by 4-C oxaloacetate – 6-C compound - citric acid Formation of intermediates 1. Reactions – Decarboxylation – substrate-level phosphorylation produces ATP – Reduction of FADH 2 and NADH + H+ 2. Net (Remember the cycle turns twice) – 2 ATP, 8 NADH, 2 FADH 2, 6 CO 2

Oxidative phosphorylation In the Box: NADH FADH 2 Out of the Box: ATP

Electron transport chain and oxidative phosphorylation 1.NADH + H+ and FADH 2 lose their electrons 1.Hydrogen – When hydrogen ions are released they are move through channel proteins from the mitochondrial matrix to the intermembrane space – They form an ‘electrochemical gradient’ Electrons – Accepted by flavins, proteins that contain Fe and S, cytochromes (pigments with Fe) – They are ‘passed’ from one to the other down the chain – Finally accepted by ½ O 2 to produce water – Movement of these electrons provide the energy to drive the hydrogen ions across the membrane

Chemiosmosis 1.Hydrogen ions will move passively through ‘ATP synthase’ 2. As they move through, the protein ‘spins’ providing energy to phosphorylate ADP and produce ATP 3. A total of 34 ATP are produced – 1 Glucose = 36 net ATP (2-Kreb’s; 2 Glycolysis)

Summary

Glycogenesis and Glycogenolysis Excess ATP is accumulated – Glycolysis declines – Excess glucose stored as glycogen or fat – Glycogenesis occurs Glycogenolysis – Glucose blood levels drop – Glycogen phosphorylase Muscle cells – Glucose-6 phosphate cannot move across the membrane – Glucose-6-phosphatase

Gluconeogenesis/Lipid oxidation When glucose levels are very low the liver can synthesize glucose – Amino acids + glycerol to produce glucose – Prevents hypoglycemia Lipid Metabolism – More energy than carbohydrates (9 kcal/g) – Glycerol (from neutral fats)--  glyceraldehyde phosphate --  Krebs (18 ATP/glycerol) – F.A. (from neutral fats)-----  2-C acetic acid + CoA (coenzyme A) ---  acetyl CoA  Krebs Beta oxidation

Lipid oxidation BETA- OXIDATION TRIGLYCERIDE METABOLISM Animation

Lipid metabolism Lipogenesis: – excess lipids are not metabolized will be stored as adipose in the hypodermis (50%) as well as other parts of the body Lipogenesis or triglyceride synthesis – occurs when ATP and glucose levels are high (enough energy available to the cells) Lypolysis: breaking down of stored fats – Glycerol converted to energy – Fatty acids

What happens if you deny yourself carbohydrates? 1. If carbohydrate levels are low 2. Oxaloacetic acid is converted to glucose (fuels the brain). 3. Oxaloacetic acid levels become low and acetyl CoA cannot enter the Kreb’s cycle – Ketogenesis and ketone bodies – Ketosis - ketone bodies accumulate in the urine – pH levels drops to dangerous levels

Protein metabolism Deamination: before proteins can be oxidized for energy must lose ammine group – Converted to pyruvate or intermediates of the Krebs Events (notes) – 1. transamination – 2. oxidative deamination – 3. ketoacid modification

Interconversions

Absorptive states

Post-absorptive state

Insulin

Glucagon and glucose

Liver Metabolism and cholesterol Cholesterol - AnimationAnimation – is an important component of bile salts; formation of vitamin D, plasma membrane and steroid hormones – 15% from the diet - the rest is made from acetyl CoA in the liver, intestinal cells Cholesterol and Triglycerides are insoluble in water – Transported via lipoproteins – Proteins regulate lipid entry and exit in the cells Types are: HDL (high protein); LDL (lower protein); VLDL; Chylomicrons

Cholesterol transport 1. Liver produces VLDL ---  transport triglycerides to adipose and other tissues  converted to LDL (much cholesterol)  transports cholesterol to peripheral tissues 2. HDL transports excess cholesterol from peripheral tissues to liver ---  broken down and becomes parts of bile 3. HDL is made in a collapsed form  moves from liver to blood and picks up cholesterol from the tissue cells and some pulled from artery walls

Cholesterol Levels 1. Liver will stimulate the production of a basal amount of cholesterol (85%) – Dieting will not override genetics up to a certain point 2. Saturated fats  stimulate liver production of cholesterol and inhibit secretion 3. Unsaturated fats  increase excretion of cholesterol – Hydrogenation and trans-fatty acids – Omega 3’s lower cholesterol levels – fatty fish Levels – HDL ( 60) is good

Feeding centers

Body temperature regulation