Krebs Cycle

The Krebs Cycle (Citric Acid Cycle) or Tricarboxylic Acid Cycle

will utilize acetyl-CoA to yield 3NADH + 3H+, 1FADH2, and 1 guanosine triphosphate (GTP)

The overall reaction of the cycle:

Acetyl-CoA + 3NAD+ + FAD + GDP3- + Pi 2- +

2H2O → 2CO2 + 3NADH + 3H+ + FADH2 +

GTP4- + CoA-SH

Reduction Reactions

synthesis of FADH2 and NADH + H+

Oxidation Reactions

oxidation of acetyl-CoA to synthesize CO2

All the enzymes for the cycle are within the mitochondrial matrix, with one exception:

Succinate dehydrogenase is bound to the inner mitochondrial membrane

Step 1:

condensation of acetyl-CoA and oxaloacetate via citrate synthase, water, and CoA-SH

• -32.2 kJ/mol

Step 2:

synthesis of isocitrate from citrate via aconitase and water to cis-aconitate to isocitrate by aconitase and water

• 13.3 kJ/mol

Step 3:

oxidation of isocitrate to yield α-ketoglutarate and CO2

• isocitrate is oxidized by hydride transfer to NAD+ or NADP+ (depending on the isocitrate dehydrogenase isoenzyme)

• decarboxylation is facilitated by electron withdrawal by the adjacent carbonyl and coordinated Mn2+

• rearrangement of the enol intermediate generates alpha-ketoglutarate

Step 4:

oxidation of α-ketoglutarate to succinyl-CoA and CO2 via α-ketoglutarate dehydrogenase complex, CoA-SH, and NAD+

• -33.5 kJ/mol

Step 5:

synthesis of succinate from succinyl-CoA via succinyl-CoA synthetase and GDP + Pi

• -2.9 kJ/mol

GTP

• an “ATP equivalent” because the liberation of a phosphate from GTP yields the same free energy values as the liberation of a phosphate from ATP

• ATP is the preferred energy source, thus a phosphate from GTP is usually transferred to ADP, by nucleotide triphosphate kinase

• GTP + ADP → GDP + ATP

Nucleotide Triphosphate Kinase

transfers a phosphate from GTP to ADP

Step 6:

oxidation of succinate to yield fumarate via succinate dehydrogenase and FAD

• 0 kJ/mol

Step 7:

hydration of fumarate to yield malate via fumarase and water

• -3.8 kJ/mol

Step 8: 

oxidation of malate to yield oxaloacetate via L-malate dehydrogenase and NAD+

• 29.7 kJ/mol