Biochem

    Cards (107)

    • Biochemistry - Metabolism
    • Course Content
      • Glycolysis
      • Entry of fructose and galactose into glycolysis
      • Fates of pyruvate
      • Gluconeogenesis
      • Cori cycle
      • Citric acid (TCA, Krebs) cycle
      • Electron transport and oxidative phosphorylation
    • Recommended Reading
      • Berg JM, Tymoczko JL and Stryer L (2012) Biochemistry (7th Edition): WH Freeman
      • Campbell MK and Farrel SO (2007) Biochemistry (6th Edition) (Thomson Brooks/Cole)
    • Metabolic Biochemistry
      • Energy is required by all living organisms as many biological processes require energy
      • Mechanical work e.g. Muscle contraction
      • Active transport
      • Synthesis of complex biomolecules from simple precursors
      • Signal transduction (environmental responses), generation of light (fire flies) and electricity (eels)
    • Muscle Contraction
      • Actin
      • Myosin
      • ATP
      • ADP
      • Ca2+
    • Active Transport/Neurotransmission
      • Na+
      • Na+
      • K+
      • K+
      • ECF
      • ICF
      • ATP
      • ADP
      • [Na+ = 150mmol/l]
      • [K+ = 110 mmol/l]
    • First Law of Thermodynamics
      "For any physical or chemical change, the total amount of energy in the universe remains constant"
    • Energy cannot be created or destroyed, but it can be converted from one form to another
    • Sources of energy for living organisms
      • Heterotrophy – Energy and volume are obtained from other organisms e.g. mammals
      • Autotrophy – Energy derived from sunlight and volume for CO2 in the atmosphere e.g. plants
      • Chemotrophs – Energy from chemical redox reactions
    • Chemoorganotrophs
      Extract energy from organic compounds by oxidation
    • Energy content of different macromolecules
      • Fats - 9 kcal/g
      • Carbohydrates - 4 kcal/g
      • Proteins - 4 kcal/g
      • Alcohol - 7 kcal/g
    • Glucose oxidation
      Glucose + 6O2 -> 6CO2 + 6H2O
    • Healthy human diet
      • Appropriate balance between carbohydrate, protein and fats
      • Energy intake and energy use also need to be balanced
    • Diets in developed countries are sometimes too high in fat or in processed carbohydrate
    • Fat contains more calories per gram than other foods and overconsumption can lead to obesity
    • Diets high in saturated lipids or cholesterol also increase the risk of developing heart disease
    • Diets high in processed carbohydrate may increase the risk of developing insulin resistance and type 2 diabetes
    • Obesity increases the risk of both heart disease and diabetes
    • Functions of Metabolism
      • Synthesis of precursors e.g. amino acids, Fatty acids, carbohydrates, proteins nucleic acids
      • Provision of energy for synthesis, mechanical work, heat production, ion pumps etc.
    • Types of metabolic pathways
      • Linear
      • Divergent
      • Convergent
    • Metabolism
      • Hundreds of different enzyme-catalysed reactions
      • Central metabolic pathways are few in number and highly conserved throughout nature
    • If energy released during breakdown of fuel molecules was simply released as heat then cells and the body would be destroyed
    • ATP
      • Energy rich molecule with high phosphoryl transfer potential
      • Contains 2 phosphoanhydride bonds on its triphosphate unit
    • ATP hydrolysis
      1. ATP + H2O -> ADP + Pi + energy
      2. ATP + H2O -> AMP + PPi + energy
    • ATP hydrolysis
      • Free energy (ΔG) is negative so thermodynamically unstable
      • However kinetically stable (in absence of a catalyst, breakdown is very slow)
      • For ATP hydrolysis ΔG = -7.3 kcal mol-1 or -10.9 kcal mol-1
    • A human hydrolyses about 55kg of ATP in 24 hours
    • Total body ATP is only 50g
    • Turnover of ATP is very high - In a sprinter average lifespan of 1 ATP molecule is 1.5 sec
    • O2 is needed to synthesise ATP efficiently so about 10,000 litres of air needs to be breathed each day
    • Substrate level phosphorylation
      Transfer of phosphoryl group from metabolites with high-phosphoryl transfer potential to ADP producing ATP
    • Oxidative phosphorylation
      • Process of ATP formation as a result of transfer of electrons from fuels via electron carriers (NADH or FADH2) to the final electron acceptor oxygen
      • In animals over 90% of ATP formed by this method, carried out in the mitochondria
    • Creatine
      • 20g/day creatine – probably increases creatine phosphate concentration in muscle
      • Normal source of creatine is 1g/day from diet, synthesised in liver from glycine, arginine and methionine
      • Total body pool approx 120g, spontaneously degrades to creatinine which is excreted in urine
    • Hexokinase
      • Kinase – phosphorylating enzyme
      • Hexo – six carbon sugar
    • Formation of glucose 6-phosphate
      • Glucose 6-phosphate is "trapped" in the cell because of its negative charge
      • The phosphoryl group begins to destabilise glucose and facilitate further metabolism
      • Equilibrium of reaction strongly favours glucose 6-phospate (effectively irreversible reaction)
    • Phosphoglucose isomerase
      Isomerase – convert from one isomer (glucose) to another (fructose)
    • Phosphofructokinase
      • Kinase – phosphorlyating enzyme
      • Phosphofructo – fructose with a phosphoryl group attached
      • Key regulatory enzyme in glycoloysis
    • Aldolase
      • Named from the reverse reaction which is an aldol condensation
      • 6 carbon sugar split into two 3 carbon sugars
    • Triose phosphate isomerase
      • Isomerase – convert from one isomer (dihydroxyacetone phosphate) to another (glyceraldehyde phophate)
      • GAP is used directly in glycolysis whereas DHAP is not
      • Isomerase converts DHAP (ketose) to GAP (aldose) for use in glycoloysis
    • Glucose has been converted to glyceraldehyde 3-phosphate but no ATP has been synthesised
    • Glyceraldehyde 3-phosphate dehydrogenase
      Dehydrogenase – transfer "high energy" electrons from complex organic molecule to NAD+ to form NADH
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