Biochemistry And Molecular Biology (BIOC0001) Notes - Metabolism

Glycolysis
Glycolysis
 Glycolysis
o Glycolysis = breakdown of glucose into 2 3 carbon compounds (first step in breakdown of glucose)
 Allows cell to use glucose to produce energy + reducing power + carbon compounds
 Reducing power and carbon compounds can be metabolised further to produce
more energy
o Oxygen and mitochondrial energy – most cells use mitochondria to produce energy = requires
oxygen for respiration
 Red blood cell
 Do not have any membrane bound organelles = no mitochondria
 Ischemic heart tissue
 Area of the heart that has had blood vessels that supply oxygen damaged = no
oxygen supply for respiration
 Active white skeletal muscle
 White muscle fibres are poor in mitochondria + have poor oxygen supply
 Fast-growing tumour
 Not enough oxygen supply
o Glycolysis = only way to produce ATP without using mitochondria or oxygen
 Glycolysis does not release all of the potential energy from glucose
 Products of glycolysis are usually further metabolised by aerobic respiration =
requires oxygen – releases more energy
 Occurs in cytosol of cells
 Sources of glucose
o Fed state
 Glucose from digestion – stomach
o Fasting state
 Glucose from glycogen – liver glycogen
o Exercise
 Glucose from glycogen – muscle glycogen
o Starvation
 Glucose from gluconeogenesis – glucose from non-carbohydrates – lactate / amino acids /
glycerol
 Breakdown of glycogen
o Glycogen phosphorylase
 Uses phosphorolysis to break bonds between glucose residues
 Produces free glucose-1 phosphate molecules
o Phospho-glucomutase
 Changes the position of the phosphate in glucose-1 phosphate = forming glucose-6
phosphate

Glycolysis Pathway
 Overall pathway
o 1 glucose  2 pyruvates
 Divided into 2 stages
 1
o 2 ATP used to prepare the glucose molecule = requires energy investment
 2
o Intermediate from preparation of glucose split into 2 molecules of
glyceraldehyde 3-phosphate
 Each glyceraldehyde 3-phosphate produces 2 ATP

,Glycolysis
 Overall
o Net production of 2 ATP
 2 ATP used in glycolysis + 4 ATP produced = net 2 ATP
o Production of 2 NADH
o Enzymes
 Kinase
 Phosphorylates compounds using ATP or dephosphorylates compounds to produce
ATP
 Dehydrogenase
 Catalyse redox reactions – one compound is reduced + other compound is oxidised
o Produces reduced coenzymes = energy currency
 Isomerase
 Catalyses structural rearrangement of compound





 Stages in glycolysis
o Stage 1
 Glucose is free to enter or leave the cell
 Hydrophilic molecule – needs transporter to move in and out of
the cell
o Surface of cell – glucose transporter binds to glucose >
changes shape > releases glucose inside or outside
(depending on concentration gradient)
 Glucose is phosphorylated by hexokinase enzyme = forming glucose 6- Glucose
phosphate
 Hexokinase enzyme – used to phosphorylate glucose
o Forming glucose 6-phosphate
 ATP hydrolysis – provides energy needed for unfavourable
reaction (phosphorylation of glucose) to occur
o Couples unfavourable reaction (phosphorylation of
glucose = positive ΔG) with favourable reaction
(hydrolysis of ATP = negative ΔG) Glucose 6-
 Resulting in negative ΔG phosphate
 Glucose 6-phosphate cannot leave the cell
 No transporter to move compound out of the cell
 Glucose 6-phosphate isomerase enzyme rearranges glucose 6-
phosphate = forming fructose 6-phosphate
 Glucose 6-phosphate isomerase rearranges glucose 6-
phosphate

Fructose 6-phosphate

, Glycolysis
o Makes it easier to phosphorylate carbon-1
 Fructose 6-phosphate is phosphorylated at carbon-1 by
phosphofructokinase 1 enzyme = forming fructose 1,6 –
bisphosphate
 Phosphofructokinase 1 – used to phosphorylate
fructose 6-phosphate
o Forming fructose 1,6-bisphosphate
Fructose 1,6-
 ATP hydrolysis – provides energy needed for bisphosphate
unfavourable reaction (phosphorylation of fructose 6-
phosphate) to occur
o Couples unfavourable reaction (phosphorylation of fructose 6-phosphate =
positive ΔG) with favourable reaction (hydrolysis of ATP = negative ΔG)
 Resulting in negative ΔG
o Stage 2
 Aldolase splits fructose 6-phosphate into dihydroxyacetone phosphate +
glyceraldehyde 3-phosphate
 Triose phosphate isomerase enzyme converts dihydroxyacetone
phosphate into glyceraldehyde 3-phosphate
 Triose phosphate isomerase TPI = kinetically perfect enzyme Glyceraldehyde
o So efficient at lowering the activation energy – rate is 3-phosphate
limited by speed at which compounds bind to active
site
 Equilibrium favours reverse reaction = formation of
dihydroxyacetone phosphate
 Glyceraldehyde 3-phosphate dehydrogenase enzyme oxidises +
phosphorylates glyceraldehyde 3-phosphate = forming NADH + 1,3- Dihydroxyaceton
bisphosphoglycerate e phosphate
 Reaction is coupled with reduction of NAD = forming 1 NADH (favourable process)
o Oxidation of glyceraldehyde 3-phosphate dehydrogenase generates enough
energy to reduce NAD + phosphorylate glyceraldehyde 3-phosphate again
1,3-  Phosphoglycerate kinase enzyme removes phosphate from 1,3-
bisphosphoglyce bisphosphoglycerate = forming 3-phosphoglycerate + ATP
rate
 Phosphorylation of ADP
o Phosphate removed is lost to ADP = forming 1 ATP
 Rearrangement of phosphate into less stable position – to produce ATP
 Phosphoglycerate mutase enzyme converts 3-phosphoglycerate 3-
into 2-phosphoglycerate phosphoglycera
 Enolase enzyme converts 2-phosphoglycerate into te
phosphoenolpyruvate
2-  Pyruvate kinase dephosphorylates phosphoenolpyruvate = forming
phosphoglycera pyruvate + ATP
te  Phosphorylation of ADP Phosphoenolpyru
o Phosphate removed is lost to ADP = forming 1 ATP vate
 Summary
o Stage 1
 Glucose molecule is free to enter or leave the cell
 To prevent molecule from leaving the cell – structure must be altered = cannot bind
to transporter protein
 Hexokinase + ATP used to phosphorylate glucose = forming glucose 6-phosphate
 Glucose phosphate isomerase rearranges glucose 6-phosphate = forming fructose 6-
phosphate