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BIOC13Winter2013 Lecture 1 Notes.docx

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Biological Sciences
Daman Bawa

BIOC13Winter2013 Lecture 1: Metabolism and Bioenergetics Metabolism o The total network of chemical reactions carried out by a living cell used to acquire and utilize energy from the environment o Anabolic reactions: synthesis of molecules from simpler components  biosynthesis o Catabolic reactions: nutrients and cell constituents are broken down to salvage their components and to generate energy  degradation Bioenergetics o Biochemical transformation of energy o Usually metabolism of ATP (NADH, NADPH) o Most important pathways are membrane associated electron transport in oxidative phosphorylation and photosynthesis Why Study Metabolism? o Knowledge of normal metabolism Is essential for understanding of abnormalities underlying disease o Control of metabolic reactions allows the organism to adapt to its environment and energy requirments o For example: exercise (high E requirement – metabolic pathways will be sped up) o And hibernation (low energy requirement) o Abnormal metabolism may result in diseases due to changes in nutrition, enzyme or hormone levels  example: diabetes o Basic metabolic pathways in most organisms are almost identical Catabolism o Stage I: large molecules in food are broken down into smaller units  digestion o Proteins get broken down into amino acids o Polysaccharides into simple sugars o Fats into glycerol and fatty acids o Absorbed by cells of the intestine and distributed thoruhgout the body o No useful energy is captured at this stage o Stage II: the smaller molecues are degraded/modified further to a few simple units that play a key role in metabolism o Mostly acetyl part of Acetyl CoA o Some energy (ATP) is produced o Stage III: complete oxidation of fuel molecules that produce most of the energy o Common pathways (Citric Acid Cycle, Oxidative Phosphorylation) o Most of the ATP is synthesized via oxidative phosphorylation o Metabolic Pathways o An interconnected series of reactions where the product of one reaction becomes the substrate for the next reaction o Every metabolic pathway has an irreversibl reaction early in the pathway that results in the product being locked in that particular pathways (First Committed Step) o Individuals reactions must be specific  one product o An entire series of reaction must be thermodynamically favoured o Pathways proceeed in one direction  irreversible so anabolic and catabolic pathways differ o Example: o 3-phosphoglycerate  3 phosphohydroxypyruvate  3 phosphoserine (this is the first committed step because is not reversible) serine 1 Types of Metabolic Pathways o linear: product of one reaction is the reactant of next > glycolysis o circular: series of reactions that regenerate initial reactant  citric acid cycle o spiral: series of reapeated reaction that break down or synthesize large molecules by removing or adding small units  breakdown/synthesis of fatty acids (2 Carbons at a time) Why bother with pathways? o Enzymes generally only catalyze one specific reaction would always be proceeding  have reaction more chances to interfere with the pathway o Allow for efficient management of energy o Molecules are synthesized or degraded by different routes o This allows metabolites to be shunted to or from other pathways o Allows multiple control points o Allows the couplidng of energetically unfavourable reactions with favourable ones o One step synthesis would require a lot of energy which is impossible to be done by the cell o If pathways were not controlled at multiple steps, then energy would be wasted since the o Metabolic reactions are enzyme mediated Role of Enzymes in Metabolic Reactions o enzymes couple reactions  energy yelding reaction is coupled to energy consuming reaction o they stabilize transition states by decreasing their energy  less energy required for the reaction to proceed which means it can proceed faster o enzymes stabilize high energy transition states wthat would make a reaction otherwise unfavourable o example: synthesis of acetyl CoA from acetate and ATP is catalyzed by acetylCoA synthetase o Enzymes have common features o high substrate specificity o active site  3D cleft that binds the substrate, o the active site is a small portion of the whole protein o multiple intermolecular sites of attraction are in the active site o a unique microenvironment is produced o a conformation change occurs once enzyme is bound to substrate o regulatory sites exist  speficic inhibition o uses co-factors or co-enzymes 2 Enzyme and reactions recur throughout metabolism o coupled reactions, activated carriers, recurring use of enzyme families and reaction types o Enzyme Classifica ons Enzyme Class Reaction Catalysed Oxidoreductases Oxidation-reduction Transferases Move functional groups Hydrolases Hydrolysis Lyases Eliminate group & form double bond Isomerases Isomerization Ligases Bond formation (ATP coupled) o Cofactors o amino acid side chains may participate in reactions o small molecules such as magnesium and zing stabilize substrate binding o coenzymes: may be added to substrate (coenzyme A), may be soluble (ATP, NAD+), may b bound prothetic groups (biotin, FAD, FMN) o coenzymes and cofactor are generally derived from vitamins  B vitamins o B2 = riboflavin, B3 = niacin, B5=pantothenate, B6=pyridoxine B Vitamin Defic
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