1. CELL RESPIRATION & METABOLISM 2
Dr. Perkins

2. OVERVIEW

3. OVERALL EQUATION
Aerobic Cellular respiration

4. ATP forms in the Mitochondrion

5. How does ATP form in the mitochondrion?
STEP 1:
Formation of Acetyl CoA.
After one 6-carbon glucose molecule breaks down into two 3-carbon pyruvate molecules, pyruvate enters the mitochondrion. A single carbon is removed and breathed out of the body as carbon dioxide. The other two carbons attach to a molecule called Coenzyme A, forming Acetyl Coenzyme A (Acetyl CoA)
When carbon dioxide is formed, energy is released in the form of electrons that are captured by NAD to form NADH + H+.
Yield 1: NADH per pyruvate.

6. The Krebs Cycle
PRODUCTS: 3 NADH
1 FADH2
1 ATP (per Pyruvate)
WASTE PRODUCTS: 2 carbon dioxide

7. The Complete Citric Acid Cycle

8. Electron Transport Chain
1. NADH or FADH2 bring electrons to the membrane

9. Electron Transport Chain
2. In a series of redox reactions, electrons are transferred from one complex to the next.

10. Electron Transport Chain
3. Some of the energy drives proton pumps.

11. Electron Transport Chain: Chemiosmosis
4. Protons accumulate in the intermembrane space, and they diffuse through ATP synthase driving the synthesis of ATP.
This is known as chemiosmosis.

12. Electron Transport Chain: Chemiosmosis
5. Oxygen attracts the electrons at the end of the chain and is converted to water.

13. Electron Transport Chain
Electrons are transferred to oxygen (oxidative)
ATP is formed (phosphorylation of ADP)
Oxidative phosphorylation

14. Detailed Accounting

15. Free Radicals Free radicals – molecules with unpaired electrons
E.g. oxygen – when it receives electrons in the ETC, sometimes oxygen free radicals known as reactive oxygen species:
Superoxide free radicals
Other free radicals:
Hydroxyl free radicals
Nitric oxide free radicals
Lead to diseases, such as atherosclerosis.
Antioxidants – molecules that scavenge free radicals; protect the body

16. Interconversion of Glucose and Glycogen

17. Glycogen
Long chain polysaccharide
Stored in liver and muscle
Storage form of carbohydrates.
Glucose storage would result in high osmotic pressure
Glycogenesis – glucose  glycogen
Actually a two step process: glucose  G6P  G1P  (glycogen synthase) Glycogen
Glycogenolysis – glycogen  (glycogen phosphorylase) G1P  G6P (cannot leak out of the cell).
Liver contains glucose-6-phosphatase;
catalyzes G6P  glucose (gluconeogenesis)

18. Glycogenesis Glycogenolysis
Glycogen synthase
Glycogen phosphorylase
Glucose from glycogen is in the form glucose 1-phosphate, so cannot leave muscle or heart cells.
Glucose-6-phosphatase
Glucose from glycogen is in the form of glucose 1-phosphate, so cannot
leave most cells.

19. Cori Cycle
Cori Cycle – the delivery of blood lactic acid to the liver for conversion into glucose.
Gluconeogenesis – the conversion of G6P, and other non-carb molecules

20. METABOLISM OF LIPIDS

21. Glucose is Converted to Glycogen or FAT
When ATP levels are high
When more food is taken into the body than is needed to meet energy demands
Acetyl CoA can also be converted to other molecules (next slide).

22. Acetyl CoA is a branchpoint
 Lipogenesis – the addition of fatty acids to glycerol

23. Why is fat our long term energy storage molecule?
1 g of fat = 9 kcal of energy
1 g of CH2O or protein = 4 kcal of energy
WHITE FAT (White adipose tissue) - where most of our triglyceride are stored.
Adipocytes
LIPASE carries out lipolysis, the breakdown of triglycerides into fatty acids and glycerol.
Free glycerol goes to the liver, where it is used to make glucose, which is sent to the blood
What happens to fatty acids?

24. β-oxidation
The process by which energy is released from free fatty acids
Enzymes remove acetic acid (2 carbons) from ends of fatty acids
Acetic acid is added to CoA  AcetylCoA
The β-carbon becomes oxidized.
Electrons are donated to NAD and FADH2 carriers for ATP synthesis
A single 16-carbon-long fatty acid yields 108 ATP

25. 1) Fatty acid is added to CoA
β-oxidation
1) Fatty acid is added to CoA
2) Hydrogen is removed  added to FAD  FADH2
FADH2 donates e- to make ATP
3) OH from H2O added to β carbon
4) Reduction of NAD  NADH
NADH donates e- to make ATP
5) Bond between alpha and β carbons breaks

26. BROWN ADIPOSE TISSUE
Involved in thermogenesis (heat production)
Especially in newborns, but also in adults.
How does it generate heat?

27. UCP-1: an uncoupling protein
Norepinephrine causes brown fat to form UCP-1
UCP-1 “uncouples” electron transport chain
H+ leak out of inner mitochondrial membrane
Less ATP is formed
Stimulates β-oxidation, which generates heat.

28. KETONE BODIES
Can provide
energy!
Times of high fat breakdown: (as in dieting, starvation, or diabetes)  fatty acids build up in blood
Liver cells convert fatty acids  acetyl CoA for energy, but also into ketone bodies.
Water-soluble molecules that circulate in the blood.
Ketosis – build up of ketone bodies in blood
During fasting
Fruity odor in breath (acetone)
Acetone has a fruity odor in breath

29. CONDITIONS RELATED TO KETONE BODIES
 Ketoacidosis: too many ketone bodies in the blood affects buffer system  serious consequences
Ketonuria: accumulation of ketone bodies in the urine. When ketone is excreted, sodium is excreted along with it. Leads to excessive urination, producing severe dehydration
These two conditions together can lead to coma, death.

30. METABOLISM OF PROTEINS

31. Nitrogen Balance NORMAL Ingest = excrete POSITIVE
Take in more than excreted
Can be used for energy
NEGATIVE
Excrete more than is taken in
Catabolic

32. PROTEIN
Provides nitrogen; replace other proteins
Excess amino acids:
used for energy
converted into carbohydrates or fat.
Bodies make 12 of the 20 amino acids. 8 of them (9 in children) come from the diet (essential).

33. Transamination New amino acids are formed in the body
Amine group is transferred from one amino acid to form another
Catalyzed by transaminases
Pyruvic acid and several citric acid cycle intermediates (called keto acids) can be converted to amino acids by adding an amine group (NH2).
Usually obtained from other amino acids
Requires vitamin B6 as a coenzyme
Each transamination requires a specific enzyme

34. aspartate transaminase
Transamination
aspartate transaminase
Pyruvic acid and several citric acid cycle intermediates (called keto acids) can be converted to amino acids by adding an amine group (NH2).
Usually obtained from other amino acids
Requires vitamin B6 as a coenzyme
Each transamination requires a specific enzyme
Alanine transaminase

35. Oxidative Deamination
In conditions of excess amino acids
Amino acids give their NH3 to
α-ketoglutarate, and glutamic acid is formed
Glutamic acid gives its NH3 to CO2
Remaining keto acids can form glucose (gluconeogenesis)
If there are more amino acids than needed, the amine group from glutamic acid can be stripped and excreted as urea in the urine.
Oxidative deamination sometimes forms pyruvic acid or another citric acid cycle intermediates.
These can be used to make energy or converted to glucose or fat.
The formation of glucose from amino acids is called gluconeogenesis and occurs in the Cori cycle.
The main substrates are 3-carbon molecules – alanine, lactic acid, and glycerol

36. Different Ways That Amino Acids are Used for Energy

37. Glycogen, Fat, and Protein
Interconversion of
Glycogen, Fat, and Protein
Glucose and ketone bodies come from the liver
Lactic acid and amino acids come from muscle
Fatty acids come from adipose tissue
Lactic acid and amino acids come from muscle
Fatty acids come from adipose tissue