Metabolism

• The main source of carbohydrates is cellulose
• The oxidation of carbohydrates is the principal source

  of energy in non photosynthetic cells
• Carbohydrates are composed of:

  1. One or many carbonyl group (C=O):
  2. At the end of a carbon chain (Aldose)
  3. Within a carbon chain (Ketose)
  4. One or more hydroxyl groups (OH) associated to carbon atoms
• • Monosaccharides : formed of a single unit (ex: glucose)
  • Disaccharides : formed of 2 units (ex: saccharose = glucose + fructose)
  • Oligosaccharides : a short chain of monosaccharide (from 3 to 10 units) their structure is non-repetitive and complex, they are often bonded to non-carbohydrate molecules (ex: glycoproteins et glycolipids)
  • Polysaccharides : long monosaccharide chains, their structure is repetitive and simple, they are linear (ex: cellulose) or branched (ex: glycogen)
• • Proteoglycans : long chain of monosaccharide units, bonded to proteins
  • Peptidoglycans : long chain of monosaccharide units bonded to each other by small peptides.
• Monosaccharides are classified according to three

  different characteristics:

  • The number of carbon atoms it contains
  • The position of the carbonyl group (aldose or ketose).
  • The chirality of the molecule (D or L configuration)
• The general formula of monosaccharides is CnH2nOn

  where n is at least 3 and no more than 8
• • If the carbonyl group is placed at the beginning of the carbon chain forming an aldehyde, this sugar will be called an aldose
  • If the carbonyl group is placed within the carbon chain and forming a ketone, this sugar will be called a ketose
• Most of the monosaccharide enantiomers found in nature are D monosaccharides
• • Configuration is determined by the farthest chiral carbon from the aldehyde or ketone
  • D is when the OH group is on the right, L is on the left

  
• A diastereomer is a stereoisomer that is not an enantiomer (a mirror image of a molecule)
• Stereoisomer example:

  • Fructose has 1 enantiomer
  • Fructose has 6 diastereomers

  
• The structure of 5-6 carbons monosaccharides is cyclic
• Reaction between the aldehyde group at C-1 (or C-2 in ketopentose) and the hydroxyl group at C-5 forms a hemiacetal linkage, producing either of the two stereoisomers; alpha or beta
• • α = if OH from the 1st carbon and distal CH2OH are on opposite sides
  • β = if OH from the 1st carbon and the distal CH2OH are on the same side

  
• Disaccharides are made of:

  • 2 monosaccharides held together by a glycosidic bond
  • The O-glycosidic bond forms between the hydroxyl group of one monosaccharide and the hydroxyl group of the other

  
• All the cellulose we have is in beta configuration, which is why we cannot digest it
• • Homo -polysaccharides: formed of one type of unit only. Ex: cellulose, glycogen and starch are polymers of glucose
  • Hetero -polysaccharides: formed of at least 2 different types of monosaccharide
• Branched polysaccharides have alpha configuration, unbranched have beta configuration
• Roles of carbohydrates:

  1. Structural
  2. Support and protect biological structures (cellulose in plants, glycosaminoglycans in cartilage and tendons)

  2. Energy source

  - Principal source of fuel, can be stored (glycogen)

  3. Metabolic

  - Can be changed into other types of molecules (Amino Acids, Fatty acids, Nucleotides)
• Glycolysis is the pathway by which six -carbon sugars are split to yield a three -carbon compound, pyruvate
• In glycolysis, the potential energy stored in the six-carbon sugars is used in the synthesis of ATP from ADP.
• Glycolysis can occurs under aerobic or anaerobic conditions
• Sugars in glycolysis come from:

  • Food/stores - Digestion of polysaccharides (starch and glycogen) and disaccharides (sucrose, maltose, lactose)
  • Metabolism - Non carbohydrate precursors (gluconeogenesis in the liver and kidney)
• • Reactions 1-5 of glycolysis are part of the energy investment phase
  • Reactions 6-10 form the energy generation phase

  
• Glycolysis Reaction 1:

  • α-D-Glucose is phosphorylated to form α-D-Glucose-6-phosphate (G6P) by hexokinase
  • Investment of an ATP (for energy coupling)
  • Highly favourable; ΔGo’ = -18.4kJ/mol
  • 1 of 3 irreversible reactions of glycolysis

  
• Hexokinase I, II and III

  • Found in multiple tissues but mainly located in skeletal muscle
  • Not specific to glucose (could used other substrates like fructose and mannose)
  • Low KM enzymes, strong affinity (around 0.04mM); just a bit of glucose is converted right away to G6P
  • Strongly inhibited by the product of the reaction, G6P
  • Operating at saturating substrate concentration

  
• Hexokinase IV

  • Also called Glucokinase
  • Found in the liver and pancreas
  • Glucose specific
  • High KM enzyme, low affinity (around 7.5mM)
  • Allow the liver to adjust its rate of glucose usage to the variations in blood glucose levels
• I: Runs at Vmax on little glucose so changes in [glucose] do not affect enzyme

  IV: Needs much higher [glucose] but is responsive to changes in [glucose]

  
• Glucose transporters (GLUT) move glucose molecules across

  the plasma membrane

  
• GLUT2

  • Found in the liver, pancreas and kidney
  • Insulin independent
  • Quickly equilibrates concentration of glucose across plasma membrane
  • Allow the hexokinase IV to adjust its rate to the concentration of glucose in the blood
• GLUT4

  • Found in the skeletal muscle, adipose tissues and heart
  • Controls how much glucose goes into muscle
  • Insulin dependent (regulated by insulin)
  • In absence of sugar, this transporter is sequestered, it is released upon insulin presence
  • Active right after a meal, but glycolysis doesn't happen right away
• Glycolysis Reaction 2:

  • α-D-Glucose-6-phosphate (G6P) is isomerized into D-Fructose-6-phosphate (F6P) by the phosphohexose isomerase
  • ΔGo’ = +1.7kJ/mol
  • Reversible
  • To make rxn go forward: increase reactants or decrease products

  
• Glycolysis Reaction 3:

  • Most regulated step
  • D-Fructose-6-phosphate (F6P) is phosphorylated at C-1 by the phosphofructokinase 1 (PFK) to generate D-Fructose-1,6-bisphosphate (FBP)
  • Consumes an ATP
  • Highly favourable, ΔGo’ = -15.9kJ/mol
  • Irreversible (2/3)

  
• Glycolysis Reaction 4:

  • D-Fructose-1,6-bisphosphate (FBP) is cleaved to generate two 3-carbons (3C) molecules : Glyceraldehyde-3-phosphate (GAP) and Dihydroxyacetone phosphate (DHAP)
  • By: fructose-1,6-bisphosphate aldolase (or just aldolase)
  • Strongly endergonic (requires energy to proceed)
  • ΔGo’ = +23.9kJ/mol (standard state conditions)ΔG = -1.3kJ/mol in cell conditions
  • Reversible

  
• Glycolysis Reaction 5:

  • Isomerization of the Dihydroxyacetone phosphate (DHAP) to Glyceraldehyde-3-phosphate (GAP) by Triose phosphate isomerase (TPI)
  • Weakly endergonic (requires energy to proceed)
  • ΔGo’ = +7.6kJ/mol, ΔG = ~ 0kJ/mol in cell conditions
  • Reversible

  
• Glycolysis Reaction 6 (start of energy generation phase):

  • Oxidation and phosphorylation of Glyceraldehyde-3-phophate (GAP) to generate 1,3-bisphosphoglycerate (BPG)
  • Reaction is catalyzed by the Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and a coenzyme, NAD+ (Nicotinamide adenine dinucleotide) an electron acceptor for the oxidation reaction
  • ΔGo’ = +6.3kJ/mol
  • Reversible

  
• OILRIG

  Oxidation Is a Loss (of electrons)

  Reduction Is a Gain (of electrons)
• Glycolysis Reaction 7:

  • Synthesis of an ATP by the transfer of a phosphoryl group from 1,3-bisphosphoglycerate (BPG)
  • Resulting product is 3-phosphoglycerate (3PG)
  • Catalyzed by Phosphoglycerate kinase
  • ΔGo’ = -17.2kJ/mol, ΔG = around 0 kJ/mol

  Reversible

  
• Glycolysis Reaction 8:

  • Isomerization of 3-phosphoglycerate (3PG) in 2-phosphoglycerate (2PG) by phosphoglycerate mutase
  • ΔGo’ = +4.4kJ/mol
  • 3PG concentration is kept high by reaction 6 and 7 driving forward reaction 8
  • Reversible