chapter 12 (part 1) citric acid cycle. gylcolysis tca cycle electron transport and oxidative...
Post on 19-Dec-2015
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The TCA Cycle(aka Citric Acid Cycle, Krebs
Cycle) • Pyruvate (actually acetate)
from glycolysis is degraded to CO2
• Some ATP is produced • More NADH is made • NADH goes on to make more
ATP in electron transport and oxidative phosphorylation
Entry into the TCA Cycle
• Pyruvate is translocated from the cytosol to the mitochondria
• Pyruvate is oxidatively decarboxylated to form acetyl-CoA
• Pyruvate dehydrogenase uses TPP, CoASH, lipoic acid, FAD and NAD+
• Acetyl-CoA then enters TCA cycle thru citrate synthase
Pyruvate Dehydrogenase
ComplexComposed of three enzymes:• pyruvate dehydrogenase (E1)
(cofactor = TPP)• Dihydrolipoamide acetyltransferase
(E2) (cofactor = Lipoamide, CoA)• Dihydrolipoamide dehydrogenase
(E3) (cofactor = FAD, NAD+)
Aconitase• Isomerization of Citrate to Isocitrate • Citrate is a poor substrate for oxidation • So aconitase isomerizes citrate to yield
isocitrate which has a secondary -OH, which can be oxidized
• Aconitase uses an iron-sulfur cluster to position citrate (binds –OH and carboxyl of central carbon)
Isocitrate Dehydrogenase
• Oxidative decarboxylation of isocitrate to yield -ketoglutarate
• Classic NAD+ chemistry (hydride removal) followed by a decarboxylation
• Isocitrate dehydrogenase is a link to the electron transport pathway because it makes NADH
• Rxn is metabolically irreversible
-Ketoglutarate Dehydrogenase
• A second oxidative decarboxylation • This enzyme is nearly identical to
pyruvate dehydrogenase - structurally and mechanistically
• Five coenzymes used - TPP, CoASH, Lipoic acid, NAD+, FAD
Succinyl-CoA Synthetase
• A substrate-level phosphorylation • A nucleoside triphosphate is made
(ATP in plants/bacteria and GTP in animals)
• Its synthesis is driven by hydrolysis of a CoA ester
Succinate Dehydrogenase• An oxidation involving FAD
• Mechanism involves hydride removal by FAD and a deprotonation
• This enzyme is actually part of the electron transport pathway in the inner mitochondrial membrane
• The electrons transferred from succinate to FAD (to form FADH2) are passed directly to ubiquinone (UQ) in the electron transport pathway
• Enzyme inhibited by malonate
Fumarase
• Hydration across the double bond
• trans-addition of the elements of water across the double bond
• Stereospecific reaction
Malate Dehydrogenase• An NAD+-dependent oxidation • The carbon that gets oxidized is the
one that received the -OH in the previous reaction
• This reaction is energetically expensive
• Go' = +30 kJ/mol
Reduced Coenzymes Fuel ATP Production
• Acetyl-CoA + 3 NAD+ + Q + GDP + Pi +2 H20 HS-CoA + 3NADH + QH2 + GTP + 2 CO2 + 2 H+
• Isocitrate Dehydrogenase 1 NADH=2.5 ATP• -ketoglutarate dehydrogenase 1 NADH=2.5
ATP• Succinyl-CoA synthetase 1 GTP=1 ATP• Sunccinate dehydrogenase 1 QH2=1.5
ATP• Malate Dehydrogenase 1 NADH=2.5 ATP
• Total of 10 ATPs gained from oxidation of 1 Acetyl-CoA
The Anaplerotic ReactionsThe "filling up" reactions
• PEP carboxylase - converts PEP to oxaloacetate
• Pyruvate carboxylase - converts pyruvate to oxaloacetate
• Malic enzyme converts pyruvate into malate
The Glyoxylate Cycle• A variant of TCA for plants and bacteria • Acetate-based growth - net synthesis of
carbohydrates and other intermediates from acetate - is not possible with TCA
• Glyoxylate cycle offers a solution for plants and some bacteria and algae
• The CO2-evolving steps are bypassed and an extra acetate is utilized
• Isocitrate lyase and malate synthase are the short-circuiting enzymes
Glyoxylate Cycle• Rxns occur in specialized organelles
(glycoxysomes)• Plants store carbon in seeds as oil• The glyoxylate cycle allows plants to
use acetyl-CoA derived from B-oxidation of fatty acids for carbohydrate synthesis
• Animals can not do this! Acetyl-CoA is totally oxidized to CO2
• Malate used in gluconeogenesis