CITRIC ACID CYCLE / TCA CYCLE / CREB CYCLE http://www.science.smith.edu/departments/Biology/Bio231/krebs.html http://www.wiley.com/legacy/college/boyer/0470003790/animations/tca/tca.htm

KREB’s cycle, TCA cycle

Differences between KREB’s cycle and glycolysis In procaryotes, glycolysis takes place in the cytosol, while the KREB’s cycle is on the plasma membrane. In eucaryotes, glycolysis in the cytosol, while the KREB’s cycle is in the mitochondria. Most of the enzymes of the KREB’s cycle is found in the mitochondrial matrix.

TCA CYCLE

Pyruvate dehydrogenase complex

What is citric acid cycle???

TPP = thiamine pyrophosphate (prosthetic group) Pyruvate Acetyl-CoA Negative feed-back inhibition TPP = thiamine pyrophosphate (prosthetic group) E1, E2, E3 are pyruvate dehydrogenase, dihydrolipoyl transacetylase, dihydrolipoyl dehydrogenase.

The regulation mechanisms are different for E1, E2 and E3.

Pyruvate dehydrogenase kinase is tightly bound to E1. Continued….. Pyruvate dehydrogenase kinase is tightly bound to E1. Phosphoprotein phosphatase is weekly bound to E1. Control of the activity of pyruvate dehydrogenase complex is exerted by the phosphorylation of E1. Phosphorylation cause inhibition (inactivation) to E1. (see previous slide). Phosphorylation is catalyzed by pyruvate dehydrogenase kinase. Pyruvate dehydrogenase kinase is activated by high-energy condition, it requires ATP to accomplish the phosphorylation step. Another enzyme, phosphoprotein phosphatase reactivates the system by removing the inhibitory phosphate group.

C-I-K-Su-Suka-Flyer-Merah-Orange Refer to Figure 12.5 (handouts given) C-I-K-Su-Suka-Flyer-Merah-Orange

pyruvate Control points Inhibited by ATP, acetyl-CoA, NADH Inhibited by ATP stimulated by ADP Control points Inhibited by ATP, NADH Steps requiring electron acceptor, either NAD+ or FAD

FROM 1 MOLECULE OF GLUCOSE H2O + Refer to Figure 12.5 (handouts given) FROM 1 MOLECULE OF GLUCOSE 2 FADH2 molecules 2 ATP molecules 3 X 2 =6 NADH molecules

Refer to Figure 12.5 (handouts given) 8 1 7 3 6 4 5

(Aldol condensation & Hydrolysis) CoA-SH

Regulation of Citrate Synthase (Step 1) Step 1 is a reversible reaction, however, the equilibrium lies in favor of citrate formation because the hydrolysis of intermediate compound, citroyl-CoA is an exergonic process. Citroyl-CoA is bound to citrate synthase during this reaction. Citrate synthase is inihibited by its substrate (acetyl-CoA & oxaloacetate), and its activity is affected by the energy status of mitochondria (low NAD+/NADH ratio inhibits). Acetyl-CoA competes with succinyl-CoA for the active site.

(Dehydration, Hydration, Isomerization)

(Oxidative decarboxylation)

Regulation of Isocitrate Dehydrogenase (Step 3) (e.g. ATP & NADH) Control of glycolysis by elevated concentrations of high-energy compounds within the mitochondria.

( Thioesterification, Decarboxylation, Oxidation)

Note: -ketoglutarate  2-Oxoglutarate (Step 1) (Step 3) (Step 4) Note: -ketoglutarate  2-Oxoglutarate

Note: -ketoglutarate  2-Oxoglutarate Regulation of activity by: Substrate availability Product inhibition Allosteric inhibition or activation by other intermediates

(Phosphorylation & Hydrolysis) Phosphorylation of GDP is a substrate-level phophorylation. The energy for this phosphorylation is derived from the hydrolysis of the thioester bond of succinyl-CoA.

(Redox: trans eliminatio of two H’s.) The only reaction in TCA cycle involving FAD.

(Hydration : additon of water)

(Redox)

GLYOXYLATE CYCLE glucose gluconeogenesis Citrate synthase In plants and in some bacteria, but not in animals, acetyl-CoA can serve as the starting material for the biosynthesis of carbohydrates. gluconeogenesis Citrate synthase 2 Acetyl-Co-A 1 Isocitrate lyase Malate synthase CoA-SH Glyoxylate + succinate

Glyoxysomes – specialized organelles in plants and are the sites of the glyoxylate cycle. VIP in germinating seeds as the fatty acids are stored in the seeds and broken down for energy during germination. First the fatty acids give rise to acetyl-CoA, which can enter the TCA cycle and go on to release energy. TCA and glyoxylate cycle can operate simultaneously. Acetyl-CoA can also serves as the starting point for the synthesis of glucose and other compounds needed by the growing seedlings.

Note: -ketoglutarate  2-Oxoglutarate