Citric acid cycle (TCA cycle) by Dr. Anurag Yadav

Citric acid cycle
TCA Cycle

1. Citric Acid cycle Dr Anurag Yadav MBBS, MD Assistant Professor Department of Biochemistry Instagram page –biochem365 Email : [email protected] MNR MEDICAL COLLEGE & HOSPITAL

2. Also know as Krebs Cycle. Krebs proposed the original name TCA (Tricarboxylic acid)

3. Functions of the Citric acid cycle 1. The final common oxidative pathway that oxidizes acetyl CoA to CO2. 2. The source of reduced co-enzymes that provide the substrate for the respiratory chain. 3. The link between catabolic and anabolic pathways ( amphibolic role). 4. Provides precursors for synthesis of amino acids and nucleotides. 5. Components of the cycle have a direct or indirect controlling effects on key enzymes of other pathways.

4. Significance of Citric acid cycle

5. STEPS of CITRIC ACID CYCLE Location: Mitochondrial matrix Krebs cycle basically involves the combination of a two carbon acetyl CoA with a four carbon oxaloacetate to produce a six carbon tricarboxylic acid, citrate.

6. In the reactions that follow, the two carbons are oxidized to CO2 and oxaloacetate is regenerated and recycled. Oxaloacetate is considered to play a catalytic role in citric acid cycle.

7. Reactions of the cycle preparatory step Acetyl CoA enters the cycle, and is completely oxidized. All the enzymes of citric acid cycle are located inside the mitochondria.

8. Reactions of citric acid cycle

9. Steps

10. ATP Generating steps in TCA Cycle 3 NADH generated 3 * 2.5 = 7.5 ATP 1 FADH2 generated 1 * 1.5 = 1.5 ATP 1 GTP generated = 1 ATP Per turn of cycle = 10 ATP are generated

11. Role of Vitamins in TCA cycle

12. Regulation of Citric Acid cycle

13. Integration of Major Metabolic Pathway carbohydrates: are metabolized through glycolytic pathway to pyruvate , then converted to acetyl CoA which enters TCA. 2. Fatty acids : through beta oxidation, are broken down to acetyl CoA and then enters this cycle. 3. Glucogenic amino acids after transamination enter at some or other points in this cycle. Ketogenic amino acids are converted into acetyl CoA.

14. Fat is burned on the wick of carbohydrates The oil in a lamp by itself cannot be lighted; the flame needs a wick Oxidation of fat need the help of oxaloacetate . Major source of oxaloacetate is pyruvate ( Carb )

15. Excess Carb are converted to Neutral fat Excess calories are deposited as fat in adipose tissue. The pathway is glucose to pyruvate to acetyl CoA to fatty acid. fat cannot be converted to glucose because pyruvate dehydrogenase reaction ( pyruvate to acetyl CoA) is an absolutely irreversible step. No Net synthesis of Carbohydrate from Fat

16. Amphibolic nature of TCA cycle TCA cycle is both catabolic and analbolic . TCA is termed as Metabolic Traffic Circle

17. Efflux of TCA cycle intermediates

18. Influx of TCA cycle intermediates

19. Anaplerotic Role of TCA cycle Greek word : Fill up The synthetic reactions depletes the intermediates of TCA cycle. Cycle will ease to operate unless the intermediates are replenished.

20. The reactions concerned to replenish or to fill up the intermediated of citric acid cycle are called anaplerotic reactions or anaplerosis .

21. Inhibitors of TCA cycle

22. Metabolic Defects Related to Krebs Cycle Though rare. Some of the defects are found to affect the operation of TCA cycle

23. Dr Anurag Yadav MBBS, MD Assistant Professor Department of Biochemistry Instagram page –biochem365 YouTube – Dr Biochem365 Email: [email protected]