L34 - introduction To Cell Metabolism 1 Flashcards
What is metabolism?
The inter-conversion of biomolecules using chemical reactions
What are catabolic reactions (degradative)?
- production of ATP and ion gradients
- production of mechanical energy (muscle contraction)
- production of reducing equivalents (NADH, NADPH)
- production of biosynthetic precursors
What are anabolic reactions (biosynthetic)?
- storage of energy
- production of macromolecules and cellular structures
What is the gibbs free energy eqn?
DeltaG = deltaG^degrees +RT ln [products]/[reactants]
What is GFE like?
- under standard conditions
- temp fixed at ~310.15K (37) R is constant (8.314 J.K^-1.mol^-1)
What are reactions like?
- in a state of flux (chemicals interconverted through successive series of steps)
- endothermic (need energy)
- driven by ATP or pyrophosphate hydrolysis
What does metabolism need to do?
Balance energy (ATP), reducing agents and the amounts of small molecules
What is stage 1 of glycolysis?
- in the cytosol
- activates glucose for meatbolism (2ATP) and rearrangement (2 C3 sugars in stage 2)
- double phosphorylation causes ring openeing of sugar
What is stae 2 of glycolysis?
- fructose-1,6-bisphosphate -> dihydroxyacetone phosphate, glyceraldehyde-3-phosphate
- dihydroxyacetone phosphate -> glyceraldehyde-3-phosphate
- NET 2glyceraldehyde-3-phosphate
What is stage 3 of glycolysis?
- each step repeated twice (2glyceraldehyde-3-phosphate produced)
- energy producing phase (2NADH, 4ATP)
What is anaerobic respiration?
- occurs in muscle, absence of oxygen
- pyruvate reduced to R-lactate (D-lactate)
- oxidises NADH to NAD+ = glycolysis continues
- R-lactate reoxidised to pyruvate with NAD+
What does the cori cycle do?
recycles R-lactate to glucose
What is the cori cycle?
- lactate transported, muscle -> liver by blood
- lactate dehydrogenase R-lactate -> pyruvate
- requires 6ATP/glucose, 2ATP from glycolysis
What is gluconeogenesis?
- in liver
- 2pyruvates/glucose
- ATP, CO2, pyruvate = oxaloacetate, exported to cytosol -> phosphoenolpyruvate
- 2ATP, NADH required
- additional enzymes needed
- phosphate allows export of glucose to other tissues
What enzymes are needed in gluconeogenesis?
- pyruvate carboxylase (ATP, CO2)
- PEP carboxykinase (ATP)
- bisphophatase
- phosphatase
What is mitochondria important for?
- aerobis respiration
- degradation of glucose and fats
- gluconeogenesis
How does the structure of mitochondria relate to its functions?
- matrix contains enzymes for tricarboxylic acid (TCA) cycle
- membranes required for ETS
What does the pyruvate dehydrogenase complex control?
Entry of pyruvate into TCA cycle
What are the pyruvate dehydrogenase complex subunits?
- pyruvate dehydrogenase (E1)
- pyruvate transferase (E2)
- dihydrolipoyl dehydrogenase (E3)
What does E1 do?
Decarboxylates pyruvate
What does E2 do?
Makes CoA (requires lipoamide)
What does E3 do?
Converts reduced lipoamide to disulfide form (requires FAD)
What are the steps in the reaction for formation of acetyl-CoA?
- TPP anion adds to pyruvate and CO2
- lipoamide disulfide added to acetyl group, redox
- disulfide exchange occurs = acetyl-CoA, reduced lipoamide
- reduced lipoamide oxidised -> disulfide form (FAD)
- FADH2 oxidised (NADH), into ETS
What is the TCA cycle?
- in catabolic and anabolic reactions
- 4 phases (8 steps)
- Acetyl-CoA -> 2CO2 (+ 3NADH, H+, FADH, GTP)
- O2 present -> reoxidation of reduced cofactors by ETS
What are the 4 phases in TCA cycle?
- condensation, rearrangement (1 and 2)
- decarboxylation (3 and 4)
- formation og GTP using phosphate anhydride bond (5)
- conversion of succinate to oxaloacetate (6-8)
What is step 1 in the TCA cycle?
- citrate synthase catalyses cond of Acetyl-CoA and oxaloacetate
- hydrolysis of CoA ester = irreversible reaction
- citrate undergoes rearrangement = isocitrate
What is stage 2 in TCA cycle?
- isocitrate -> B-ketoacid using NAD+
- B-ketoacid loses CO2
- 2-oxoglutarate -> succinyl-CoA by multi-enzyme complex
What is stage 3 in the TCA cycle?
- CoA displaced by Pi = mixed acid anhydride
- phosphate transferred to an active site His
- transfer of phosphate group onto GDP forms GTP
What is stage 4 of the TCA cycle?
- succinate into oxaloacetate
- produces reduced cosubstrates (used in ETS to make ATP)
How do you convert succinate into oxaloacetate?
- desaturation of C-C bond using FAD
- hydration of db to form S- malate
- NAD+ dependent oxidation to reform oxaloacetate (driven by removal of oxaloacetate, conversion to citrate)
