TCA Cycle or Krebs cycle - Energtics ,Regulation

TCA cycle Central pathway connecting almost all the individual metabolic pathways (either directly or indirectly).

1. THE CITRIC ACID CYCLE ( TCA CYCLE) Dr.M.Sabarinathan M.Sc., PhD (Medical Biochemistry) Assistant Professor Dept of Biochemistry

2. TCA CYCLE Introduction Definition Location Reactions of TCA cycle Energetics of TCA cycle Role of Vitamins in TCA cycle Inhibitors of TCA cycle Regulation of TCA cycle Amphibolic nature Anaplerosis

3. Introduction The complete cycle was proposed by Sir Hans Krebs in 1937 (Nobel prize, 1953) based on the studies of oxygen consumption in pigeon breast muscle. Hence Known as Krebs cycle Tricarboxylic acids (citrate, cisaconitate and isocitrate ) participate in this cycle I mportant pathway for the energy supply to the body 65-70% of the ATP synthesized in Krebs cycle . TCA cycle Central pathway connecting almost all the individual metabolic pathways (either directly or indirectly). Acetyl Co is derived from the metabolism of fuel molecules as amino acids, fatty acids, and carbohydrates.

4. TCA Cycle Definition Citric acid cycle essentially involves the oxidation of acetyl CoA to CO2 and H2O. Location : Mitochodria

5. Role of Oxaloacetate TCA Cycle involves the combination of a two carbon acetyl CoA with a four carbon oxaloacetate to produce a six carbon tricarboxylic acid, citrate . T he two carbons (Acetyl coA ) are oxidized to CO2 and oxaloacetate is regenerated and recycled . Oxaloacetate is considered to play a catalytic role in citric acid cycle.

6. Role of Oxaloacetate The TCA Cycle called as cycle because the starting molecule ,oxaloacetate( 4 carbons), is regenerated at the end of the cycle Throughout the cycle Oxaloacetate is progressively transformed into several different molecules ( as carbon atoms are added to and removed from it), but at the end of the cycle it always turn back into oxaloacetate to be used again. The released energy captured as electron shuttles (NAD, FAD) are reduced to ( NADH, FADH)

7. Sources of Acetyl CoA

8. Amphibolic nature TCA cycle is both catabolic & anabolic nature, hence regarded as amphibolic . TCA cycle is actively involved I gluconeogenesis, transamination and deamination Anabolic reactions * Oxaloacetate Precursors for aspartate * α - ketoglutarate Precursors for glutamate above these to required for the synthesis of other non-essential amino acids, purines and pyrimidines

9. Succinyl CoA is used for the synthesis of HEME Mitochondrial citrate is transported to the cytosol , & it is cleaved to provide acetyl CoA for the synthesis of fatty acids, sterols.

10. Anaplerosis or anaplerotic reactions The reactions concerned to replenish or to fill up the intermediates of citric acid cycle are called anaplerotic reactions or anaplerosis (Greek : fill up).

11. Anaplerosis or anaplerotic reactions Pyruvate to oxaloacetate catalyse by pyruvate carboxylase, which requires ATP. Pyruvate is converted to malate by NADP+ dependent malate dehydrogenase ( malic enzyme).