VII. Metabolism Overview and Digestion. A. Introduction

Transcription

1 VII. Metabolism verview and Digestion A. Introduction 1. All living organisms require a constant supply of energy a. Basic problem (1) Living organisms are working against natural tendency for things to become more disorganized (Second Law of Thermodynamics) (2) Use energy to create the order we associate with life Slide b. What is energy used for? (1) Biosynthesis - making the molecules required for life (2) Movement (3) Active transport - moving substances against their concentration gradient 2. Source of energy Slide a. In most cases energy source can be traced back sun b. Light energy captured by organisms capable of photosynthesis - green plants, photosynthetic bacteria and some algae c. Light energy converted into chemical energy - fixing 2 to make carbohydrate d. et reaction: e. Plants use this carbohydrate together with nitrogen (provided by soil bacteria) and other chemical to make all their molecules f. rganic molecules of plants used by animals as energy sources and as sources of molecules they can t make, for example essential amino acids and fatty acids g. early all energy required by animals generated by oxidation (burning) of carbohydrates and lipids (1) Sample overall reactions (a) arbohydrate (3.8 kcal /g) Lipid (fatty acid) (9.1 kcal /g) (2) These reactions show the energy relationships between plants and animals (a) Plants use light and 2 to make fuel and 2 Animals burn fuel with 2 and make 2 3. Entire set of reactions that occur in an organism called metabolism a. Major divisions of metabolism Slide (1) Anabolism - building things up - has following characteristics (a) Divergent - starts with core processes and diverges to give multitude of products Energy-requiring (c) Reductive - requires input of electrons for reduction (2) atabolism - breaking things down - has following characteristics (a) onvergent - pathways converge to central processes Energy-producing (c) xidative - gives off electrons b. ommunication between catabolism (energy and electron-producing) and anabolism (energy and electron-requiring) (1) Uses molecules common to both processes (common intermediate principle) Slide (2) Primary energy carrier - ATP (other molecules such as GTP, TP, UTP, used to lesser extent) (a) Formed during oxidation of fuels (some energy also released as heat) Used for energy-requiring processes (3) Primary electron carrier - AD (a) AD + used as major electron acceptor during catabolism AD (or ADP) used as electron donors during anabolism 49

2 Slide 4. atabolism can be pictured as being composed of three stages Slide a. Stage 1:Breakdown of macromolecules into their building blocks (1) Proteins amino acids (2) Polysaccharides, disaccharides monosaccharides (3) Fats fatty acids + glycerol b. Stage 2: onversion of amino acids, monosaccharides, fatty acids, glycerol into few smaller molecules - main one is acetyl oa c. Stage 3: Final oxidation of smaller molecules (primarily acetyl oa) to produce ATP Slide 5. Anabolism can be pictured as being composed of two stages Slide a. Stage 1: Energy (ATP) and reduction (electrons) used to make building blocks for maromolecules b. Stage 2: Building blocks used to make macromolecules such as proteins, polysaccharides, triacylglycerols, and nucleic acids (also requires energy) 5. ellular location of metabolic processes Slide a. ytosol - fluid part of cytoplasm (all cellular contents between outer plasma membrane and the nucleus) (1) arbohydrate pathways: glycolysis, glucose synthesis, glycogen breakdown and synthesis (2) Fatty acid synthesis b. ucleus - DA and RA synthesis c. Ribosomes - protein synthesis d. Lysosomes - cellular recycling center - digest and recycle old cell parts e. Endoplasmic reticulum (ER) (1) Smooth ER - synthesis of fats and steroids (2) Rough ER - protein synthesis and protein processing f. Mitochondrion Slide (1) itric acid cycle (2) Electron transport system (3) Fatty acid oxidation 50

3 B. ATP and ther Energy-Rich Phosphates 1. Key point - these molecules all have significant potential for reaction - usually measured by their potential to be hydrolyzed 2. ATP a. Basic comparative reaction - hydrolysis ATP + 2 ADP + P i kcal (P i = inorganic phosphate, 2 P 4, P4 2 ) b. Says that hydrolysis of one mol of ATP under standard conditions will release 7.3 kcal of energy. c. auses of instability - lies in the structure of the molecule pyrophosphate bonds 2 P P P 2 adenosine triphosphate (ATP) (1) It is the two pyrophosphate bonds that have greatest potential for hydrolysis (2) ne reason is charge repulsion between negatively-charged phosphate groups (3) Products have more resonance stability (electrons able to spread out more) 3. ther energy-rich phosphates Slide a. Acyl phosphates (mixed anhydrides) (1) 1,3 - bisphosphoglycerate phosphoglycerate + P i kcal (2) Acetyl phosphate + 2 acetate + P i kcal b. Guanidine phosphates (1) reatine phosphate + 2 creatine + P i kcal (2) Arginine phosphate + 2 arginine + P i kcal c. Pyrophosphates (1) ther nucleoside triphosphates (TP, TTP, GTP, UTP) - energy released similar to ATP (2) ADP and other nucleoside diphosphates ADP + 2 AMP + P i kcal (3) Pyrophosphate PP i P i kcal d. Sugar phosphate (phosphate esters) (1) Glucose-1-phosphate + 2 glucose + P i kcal (2) Fructose-6-phosphate + 2 fructose + P i kcal (3) AMP + 2 adenosine + P i kcal (4) Glucose-6-phosphate + 2 glucose + P i kcal Slide 4. ATP occupies central position a. ompounds above it are able to transfer phosphate to ADP and produce ATP b. ompounds below it can be made by phosphorylation using ATP 51

4 . Key oenzymes in Metabolic Pathways Slide 1. AD + /AD - nicotinamide adenine dinucleotide (coenzyme form of vitamin niacin) a. Participates in oxidation-reduction reactions b. Reaction: AD e + + AD c. This coenzyme is mobile - goes into and out of active site and carries electrons Slide 2. FAD/FAD 2 - flavin adenine dinucleotide (coenzyme form of vitamin riboflavin) a. Participates in oxidation-reduction reactions Slide (key one formation of carbon-carbon double bonds) b. Reaction: FAD + 2 e FAD 2 c. This coenzyme is not mobile - remains in enzyme active site Slide 3. oenzyme A a. Serves as a carrier of acyl groups attached to thiol (-S) group R + S oa R S acyl group acyl oa b. Most common one is acetyl oa 3 S oa c. In this form the acyl group is activated (energy-rich) d. This is the coenzyme form of the vitamin pantothenic acid oa D. Ingestion, Digestion and Absorption of Macromolecules - Stage I of Metabolism 1. utline a. Starts with ingestion and chewing to decrease particle size - facilitate enzyme action later b. Digestion (enzymatic) continues in mouth, stomach and small intestine (digestive tract) c. Molecules produced are absorbed in small intestine into circulatory systems 2. Details Slide a. Mouth (1) Mastication - break down food into smaller pieces (2) Food lubricated with mucin (component of saliva) (3) Digestion of polysaccharides begins with -amylase in saliva - yields mixture of dextrins, maltose and glucose b. Stomach (1) Arrival of food causes secretion of gastrin (hormone) (2) Gastrin stimulates secretion of gastric juice (p ~ 1) by gastric glands (a) l from parietal cells Pepsinogen from chief cells (3) Pepsinogen (zymogen) activated by low p - becomes pepsin (a) Pepsin is endopeptidase (p optimum ~ 1) atalyzes hydrolysis of peptide bonds containing large nonpolar groups (Phe, Trp, Tyr, Leu, Met) (4) Final product of mechanical churning and proteolysis is thin, watery liquid called chyme (5) Passes into upper part of small intestine (duodenum) 52

5 c. Small intestine (1) Arrival of chyme leads to secretion of several hormones - in turn cause additional effects (a) Entergastrone - feeds back to inhibit secretion of gastric juice in stomach Secretin - stimulates secretion of pancreatic juice containing bicarbonate neutralizes acidity in chyme (c) Pancreozymin/cholecystokinin - effect is two-fold (i) Stimulates release of bile from gall baldder - emulsifying agent for lipids (ii) Stimulates pancreas to secrete mixture of digestive enzymes and zymogens - α-amylase, lipase, trypsinogen, chymotrypsinogen, procarboxypeptise, proelastase, etc. (2) Digestion processes Slide (a) arbohydrates (i) (c) Starch - process that had begun in mouth finished off by pancreatic α-amylase and debranching enzyme (ii) Maltose, lactose, sucrose - hydrolysis catalyzed by maltase, lactase, and sucrase located in membranes of intestinal cells (iii) Final product is mixture of monosaccharides Proteins (i) Zymogens activated - enteropeptidase from intestinal cells activattes trypsinogen which in turn activates other zymogens (ii) Trypsin, chymotrypsin are endopeptidases (iii) arboxypeptidase - catalyzes hydrolysis of peptide bonds starting from carboxyl terminus of protein (iv) Intestinal juice contains aminopeptidase (catalyzes hydrolysis of peptide bonds starting from amino terminus of protein; and dipeptidase and tripeptidase (v) Final product is mixture of amino acids Lipids (Triglycerides) (i) Emulsified by bile - make lipid more accessible to enzyme attack (ii) Pancreatic lipases catalyze hydrolysis to give fatty acids and 2-monoglycerides d. Absorption of digested nutrients (1) ccurs primarily in small intestine through projections (villi) that contain many blood vessels and central lymphatic vessels (2) Monosaccharides and amino acids - taken into blood vessels by active transport - go primarily to liver for additional processing (3) Monoglycerides and fatty acids (a) (c) Taken into central lymphatic vesels (passive transport) Reassembled into triglycerides and combined with proteins to give chylomicrons Transported via lymphatic system to thoracic duct and into circulatory system 53