glycolysis 1

metabolism

process through which living systems acquire and utilize the free energy they need to carry out their various functions

stages of metabolism

1. interconversion of polymers and complex lipids with monomeric intermediates

2. interconversion of monomeric sugars, amino acids, and lipids with simpler organic compounds

3. degradation or synthesis from inorganic compounds, including CO₂, H₂O, and NH₃

central pathways of energy metabolism

• glycolysis

• oxidative phosphorylation

tissues that synthesize glucose

• liver

• kidney cortex

tissues that use glucose as their primary energy source

• brain and nervous tissue

• muscle

• kidney medulla

• erythrocytes

• testes

glycolysis

• first step of glucose oxidation

• 10 step pathway

• includes energy investment and generation phases

• form of fermentation

fermentation

• NADH produced earlier in the pathway is reoxidized to NAD⁺ by transfer of electrons to some electron acceptor

• this ensures that there is enough NAD⁺ available for the cell to continue to produce ATP via glycolysis under anaerobic conditions

step 1 of glycolysis

glucose is phosphorylated by hexokinase, becoming glucose-6-phosphate (G6P), first ATP invested

step 2 of glycolysis

gluose-6-phosphate is converted to fructose-6-phosphate by glucose-6-phosphate isomerase

step 3 of glycolysis

fructose-6-phosphate is phosphorylated by phosphofructokinase, becoming fructose-1,6-bisphosphate (FBP), second ATP invested

step 4 of glycolysis

fructose-1,6-bisphosphate is cleaved into glyceraldehyde-3-phosphate (GAP) and dihydroxyacetone phosphate (DHAP) by aldolase

step 5 of glycolysis

dihydroxyacetone phosphate is converted into glyceraldehyde-3-phosphate by triose phosphate isomerase

step 6 of glycolysis

glyceraldehyde-3-phosphate is oxidized and phosphorylated into 1,3-bisphosphoglycerate (BPG) by glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

step 7 of glycolysis

1,3-bisphosphoglycerate is phosphorylated by phosphoglycerate kinase, becoming 3-phosphoglycerate (3PG), first 2 ATPs generated

step 8 of glycolysis

3-phosphoglycerate is converted into 2-phosphoglycerate (2PG) by phosphoglycerate mutase

step 9 of glycolysis

2-phosphoglycerate is dehydrated by enolase, becoming phosphoenolpyruvate (PEP)

step 10 of glycolysis

phosphoenolpyruvate is phosphorylated by pyruvate kinase, becoming pyruvate, second 2 ATPs generated

proportion of glucose energy captured in ATP in glycolysis

ΔG°’ of ATP hydrolysis / ∆G°’ of glucose oxidation = ~2%

lactate fermentation

• pyruvate + NADH + H⁺ ⇌ lactate

• ∆G°’ = -25.1 kJ/mol

• in conditions of low/no O₂

ATP

• main form of energy in cells

• favoured as energy form because of disequilibrium with ADP

catabolism

• breakdown of complex substances into simple substances

• releases energy in the form of ATP production

anabolism

• building of simple substances into complex substances

• uses energy in the form of ATP consumption

substrate cycle

coupled anabolic and catabolic pathways

futile cycles

substrate cycles in which no useful work is done, more ATP is consumed than produced

energy yield of glycolysis

• 2 ATP used in energy investment phase

• 4 ATP produced in energy investment phase

• net 2 ATP produced

• 2 NADH produced in energy investment phase → 5 ATP at electron transport chain

• total net 7 ATP produced

purpose of glucose phosphorylation in first step of glycolysis

traps glucose in the cell, commits glucose for use in glycolysis or glycogen synthesis

phosphofructokinase

• rate-limiting enzyme

• dictates speed of glycolysis

coupling of steps 6 and 7 of glycolysis

• step 6: 1,3-bisphosphoglycerate has high phosphoryl transfer potential (wants to give away phosphate) → unfavourable reaction

• step 7: substrate level phosphorylation → favourable reaction

• together, overall energetically favourable: (+6.3 kJ/mol) + (-17.2 kJ/mol) = (-10.9 kJ/mol)