1. Introduction to Biochemistry & Biotechnology
Lecture #14

2. Lehninger
Principles of Biochemistry
Chapter 14-23
Overview of Metabolic Pathways-II

3. Chapter 16
The Citric Acid Cycle
(Krebs cycle/TCA cycle)

4. Cellular Respiration
Respiration
Respiration refers to a multicellular organism’s uptake of O2 and release of CO2.
Cellular respiration refers to the molecular processes by which cells consume O2 and produce CO2.
Respiration is more complex than glycolysis and is believed to have evolved much later, after the appearance of cyanobacteria.
The metabolic activities of cyanobacteria account for the rise of oxygen levels in the earth’s atmosphere, a dramatic turning point in evolutionary history.
Q1. What is cellular respiration?
Q2. Which organism is responsible for the oxygenation of early earth?

5. Catabolism and respiration
Cellular Respiration
Catabolism and respiration
Q1. Diagrammatically show the three stages of cellular respiration for the catabolism of proteins, fats, and carbohydrates.

6. Citric Acid Cycle/Krebs Cycle/Tricarboxylic Acid (TCA) Cycle
Cellular Respiration
Citric Acid Cycle/Krebs Cycle/Tricarboxylic Acid (TCA) Cycle
Q1. What is citric acid cycle?
Q2. Who discovered the citric acid cycle?

7. Cellular Respiration
Production of Acetyl-CoA (Activated Acetate) by Pyruvate Dehydrogenase Complex
Oxidative decarboxylation reactions are oxidation reactions in which a carboxylate group is removed, forming carbon dioxide.
Q1. Draw the structure of the activated form of acetate in biological systems.
Q2. Draw the structure of coenzyme A.
Q3. Which enzyme catalyzes the conversion of pyruvate to acetyl-CoA?
Q4. Show the overall reaction catalyzed by the pyruvate dehydrogenase complex.
Q5. What is oxidative decarboxylation? Give an example.

8. Citric Acid Cycle takes place in mitochondria
Cellular Respiration
Citric Acid Cycle takes place in mitochondria
Like the conversion of pyruvate to acetyl CoA, the citric acid cycle takes place in the matrix of the mitochondria. Almost all of the enzymes of the citric acid cycle are soluble, with the single exception of the enzyme succinate dehydrogenase, which is embedded in the inner membrane of the mitochondrion.
Q1. Where does the conversion of pyruvate to acetyl CoA occur in a cell?
Q2. Where does citric acid cycle take place in a cell?
Q3. Which enzyme of citric acid cycle is bound to the inner membrane of mitochondria?
Q4. Which pathway is a nearly central metabolic pathway?
Q5. What is the importance of citric acid cycle with respect to catabolism?
No question on the image of this slide.

9. Citric Acid Cycle has Eight steps
Cellular Respiration
Citric Acid Cycle has Eight steps
Q1. Diagrammatically show the citric acid cycle with the name of all the enzymes involved.
Q2. Where does citric acid cycle take place in prokaryotes?
Q3. How many decarboxylation reactions take place in one round of citric acid cycle?
Q4. How many NADH, FADH2 and nucleoside triphosphates are formed after oxidation of one acetyl-CoA?
Q5. How many molecules of ATP are formed in each round of citric acid cycle? (Answer: 0 or 1)?

10. Citric Acid Cycle Components are important Biosynthetic Intermediates
Cellular Respiration
Citric Acid Cycle Components are important Biosynthetic Intermediates
Example 1: α-Ketoglutarate and oxaloacetate can, for example, serve as precursors of the amino acids aspartate and glutamate by simple transamination (Chapter 22). Through aspartate and glutamate, the carbons of oxaloacetate and α-ketoglutarate are then used to build other amino acids, as well as purine and pyrimidine nucleotides.
Example 2: Oxaloacetate is converted to glucose in gluconeogenesis (see Fig. 15–15).
Example 3: Succinyl-CoA is a central intermediate in the synthesis of the porphyrin ring of heme groups, which serve as oxygen carriers (in hemoglobin and myoglobin) and electron carriers (in cytochromes) (see Fig. 22–23).
Q1. Why citric acid cycle is called an amphibolic pathway? Give two examples.
No question in exam on the image of this slide.

11. Anaplerotic reactions replenish Citric Acid Cycle intermediates
Cellular Respiration
Anaplerotic reactions replenish Citric Acid Cycle intermediates
Q1. What are anaplerotic reactions?
Q2. Give two examples of anaplerotic reactions with the name of the tissue/organism where they take place.
Q3. Write the name of two enzymes that are involved in anaplerotic reactions.

12. Regulation of the Citric Acid Cycle
Cellular Respiration
Regulation of the Citric Acid Cycle
Q1. Name of the three enzymes of the citric acid cycle that regulate the flux through the cycle.
Q2. Explain how the pyruvate dehydrogenase complex is regulated.
No question on the image of this slide in exam.

13. The Glyoxylate Cycle: Vertebrates cannot make Glucose from Fatty Acids
Cellular Respiration
The Glyoxylate Cycle: Vertebrates cannot make Glucose from Fatty Acids
Q1. Why vertebrates cannot synthesize glucose from acetate?
Q2. Why vertebrates cannot synthesize glucose from fatty acids?

14. The Glyoxylate Cycle: Glyoxysomes and Peroxisomes
Cellular Respiration
The Glyoxylate Cycle: Glyoxysomes and Peroxisomes
Peroxisomes are organelles with single membrane that contains catalase, peroxidase, and other oxidative enzymes and performing essential metabolic functions, as the β-oxidation of fatty acids and the decomposition of hydrogen peroxide.
Glyoxysomes are specialized peroxisomes found in plants (particularly in the fat storage tissues of germinating seeds) and also in filamentous fungi. 
Q1. What are peroxisomes and glyoxysomes?
Q2. Which of the followings is not found in animal cells?
-Mitochondria, Peroxisome, Lysosome, Glyoxysome. (Answer: Glyoxysome)
No question on the image of this slide in exam.

15. The Glyoxylate Cycle is a variation of the Citric Acid Cycle
Cellular Respiration
The Glyoxylate Cycle is a variation of the Citric Acid Cycle
The glyoxylate cycle, a variation of the tricarboxylic acid cycle, is an anabolic pathway occurring in plants, bacteria, protists, and fungi. The glyoxylate cycle centers on the conversion of acetyl-CoA to succinate for the synthesis of carbohydrates.
Q1. What is the glyoxylate cycle?
Q2. What is the importance of the glyoxylate cycle?

16. Cellular Respiration
The Glyoxylate Cycle in Plants allow production of Carbohydrates from Fatty Acids
Q1. Diagrammatically show how plants can use the glyoxylate cycle to produce carbohydrates from fatty acids.

17. Cellular Respiration
The Glyoxylate Cycle in Plants allow production of Carbohydrates from Fatty Acids
Q1. Explain how carbohydrates are formed in plants from acetyl-CoA.

18. Next Lecture: Overview of Metabolic Pathways-III
Reference Textbook: Lehninger Principles of Biochemistry
4th or 5th Edition
Chapters 14-23
David L. Nelson, Michael M. Cox WH Freeman & Company,
New York, USA