Chapter 25: Metabolism. Introduction to Cellular Metabolism Figure 25–1 Formation of Organic...

Chapter 25:

Metabolism

Introduction to Cellular Metabolism

Figure 25–1

Formation ofOrganic Molecules

Energy productionbegins in cytosol

Energy is captured to produce ATP

Energy

• Large food molecules contain energy– Energy in the form of chemical bonds– Work required to liberate energy

• ATP: breaking the P bond provides

energy for cells

ATP ADP + P + free energy from food

Food Energy + ADP + P ATP

(This ATP permits anabolism)

Energy

• Cells break down organic molecules to obtain energy:– used to generate ATP

• Most energy production takes place in mitochondria

Essential Materials

• Oxygen – absorbed at the lungs

• Water

• Nutrients: absorbed at digestive tract– vitamins– mineral ions– organic substrates

Materials Transport

• Cardiovascular system:– carries materials through body

• Materials diffuse:– from bloodstream into cells

Metabolism

• Refers to all chemical reactions in an organism

• Includes all chemical reactions within cells

• Provides energy to maintain homeostasis and perform essential functions

Essential Metabolic Functions

• Metabolic turnover:– periodic replacement of cell’s organic

components

• Growth and cell division

• Special processes:– secretion– contraction– propagation of action potentials

The Nutrient Pool• Contains all organic building blocks cell needs:

– to provide energy– to create new cellular components

• Is source of substrates for catabolism and anabolism– Catabolism:

• Is the breakdown of organic substrates • Releases energy used to synthesize high-energy

compounds (e.g., ATP)

– Anabolism:• Is the synthesis of new organic molecules via forming

new chemical bonds

Nutrient Use in Cellular Metabolism

Figure 25–2 (Navigator)

Organic Compounds

• Glycogen (carbohydrates) short carbon chains – most abundant storage carbohydrate– a branched chain of glucose molecules

• Triglycerides fatty acids and glycerol– most abundant storage lipids– primarily of fatty acids

• Proteins amino acids– most abundant organic components in body– perform many vital cellular functions

KEY CONCEPT

• There is an energy cost to staying alive • Even at rest cells must spend ATP to:

– perform routine maintenance– remove and replace structures and

components

• Cells spend additional energy for vital functions:– growth– secretion– contraction

Oxidation-Reduction Reactions (Redox Rxns)

• Oxidation = the removal of electrons (Or addition of oxygen)

• Reduction = the addition of electrons

• These reactions are always coupled– One molecule must be oxidized while another is

reduced

A-e’ + B A + B-e’

• Oxidized molecule (A): Loses energy OIL

• Reduced molecule (B): Gains energy RIG

Oxidation-Reduction Reactions (Redox Rxns)

• Cells perform dehydrogenation reactions– Hydrogen (1 proton + 1 electron) is exchanged

instead of a free electron, but this is still a redox reaction

• Catabolism of large molecules result in reduced carrier compounds – e.i. ADP ATP; NAD NADH; FAD FADH2

– These reduced compounds are later oxidized to generate ATP

ATP Production• Requires the addition of a phosphate to ADP• Two Methods for ATP Productions

1. Substrate Level Phosphorylation- High energy phosphate is transferred directly from a

substrate to ADP forming ATP

2. Oxidative Phosphorylation- Electrons are transferred from an organic compound to

a cofactor carrier molecule (e.g. NAD+)- Electrons are passed through other carriers (the

electron transport chain) to a final acceptor (oxygen)- The passing of electrons releases energy that is

harvested to add a phosphate to ADP- Process is called chemiosmosis.

What are the basic steps in glycolysis, the TCA cycle, and the electron transport

system?

Carbohydrate Catabolism (Metabolism)

• Carbohydrates are the primary source of cellular energy for most organisms

• Glucose is the most commonly used carbohydrate and will always be used first

• Generates ATP and other high-energy compounds by breaking down carbohydrates:glucose + oxygen carbon dioxide + water

Carbohydrate Catabolism (Metabolism)

Two methods for ATP productions via catabolism of glucose

1. Cellular Respiration- Requires oxygen to serve as the final electron

acceptor in a series of redox reactions- Generate ATP by oxidative phosphorylation

- Most efficient method of ATP production- 1 glucose generates 36 ATP

- Involves reaction performed inside the mitochondria

Carbohydrate Catabolism (Metabolism)

Two methods for ATP productions via catabolism of glucose

2. Fermentation- Requires an organic molecule to serve as the final

electron acceptor- Can be done in the absence of oxygen- ATP is synthesized using substrate level

phosphorylation- Less efficient, 1 glucose generates 2 ATP

- In humans, results in lactic acid

Anaerobic Vs. Aerobic RespirationGlycolysis

• Anaerobic reactions: Fermentation– Do not require oxygen– Example: Glycolysis

• Breaks down glucose in cytosol:– into smaller molecules used by mitochondria

• Aerobic reactions: Cellular Respiration– Occur in mitochondria:

• consume oxygen • produce ATP

Aerobic Respiration of GlucoseC6H12O6 + 6O2 6 CO2 + 6H2O

Three Stages1. Glycolysis

- Oxidation of glucose to pyruvic acid- Some ATP and NADH produced

2. Citric Acid Cycle- Oxidation of acetyl to carbon dioxide- Some ATP, NADH and FADH produced

3. Electron Transport Chain- NADH and FADH2 are oxidized providing electrons for redox

reactions - coenzymes that function to transport electrons in the form of

hydrogen

- Reduce oxygen to generate ATP- Majority of ATP is produced at this step

Nutrient Use in Cellular Metabolism

Figure 25–2 (Navigator)

Glycolysis (Anaerobic Process)• Does not require oxygen• Occurs in cytoplasm• 10 step metabolic pathway:

– Catabolizes and oxidizes one 6-carbon glucose molecule into two 3-carbon pyruvic acid molecules

– Generates 2 ATP by substrate level phosphorylation

• Many cells can survive on glycolysis alone– Not very efficient– Generates lactic acid as a waste product

• Needs to be removed and processed to prevent– Drastic alterations in pH– Loss of homeostasis

Glycolysis Factors

• Glucose molecules

• Cytoplasmic enzymes

• ATP and ADP

• Inorganic phosphates

• NAD (coenzyme)

Two Stages in Glycolysis

1. Preparatory Stage:- Enzyme phosphorylates last (sixth) carbon

atom of glucose molecule:1. Glucose-6-phosphate is formed using 1 ATP

molecule- traps glucose molecule within cell

2. Fructose 1,6-bisphosphate is formed using 1 ATP

– Therefore, two ATP molecules are used to phosphorylate one 6-carbon glucose and catabolize it into two 3-carbon molecules

Two Stages in Glycolysis

2. Energy Conservation Stage:– the two 3-carbon molecules are oxidized to

generate two 3-carbon pyruvic acid molecules

– Two NAD+ molecules are reduced to two NADH molecules

– 4 ATP molecules are produced by substrate level phosphorylation

– net gain 2 ATP per 1 glucose

Summary of Glycolysis

1 glucose + 2 NAD+ + 2 ADP + 2P

2 pyruvic acid + 2 NADH + 2H+ + 2 ATP

Aerobic Reactions

• If oxygen supplies are adequate:– mitochondria absorb and break down pyruvic

acid molecules

Mitochondrial Membranes

• Outer membrane:– contains large-diameter pores– permeable to ions and small organic

molecules (pyruvic acid)

• Inner membrane:– contains carrier protein– moves pyruvic acid into mitochondrial matrix

• Intermembrane space:– separates outer and inner membranes

Mitochondrial ATP Production

• H atoms of pyruvic acid:– are removed by coenzymes– are primary source of energy gain

• C and O atoms:– are removed and released as CO2

– process of decarboxylation

The TCA Cycle

TCA CyclePLAYPLAY

Figure 25–4a (Navigator)

Decarboxylation

• Preparation of the Citric Acid Cycle• First step in aerobic process of glucose

metabolism (oxygen is necessary)• 3 carbon pyruvic acid is decarboxylated

into carbon dioxide and a 2 carbon acetyl• Acetyl is attached to coenzyme A (serves

as a carrier) and one NAD+ is reduced to NADH

• Occurs in the matrix of the mitochondria

Summary of Decarboxylation

2 pyruvic acid + 2 NAD+ + 2 CoA

2 Acetyl CoA + 2 CO2 + 2 NADH

Citric Acid Cycle• a.k.a. Kreb’s Cycle or Tricarboxylic Acid Cycle• Aerobic metabolism of glucose involves

– 8 enzymatic reactions occurring in the mitochondrial matrix• Function to reduce the coenzyme NAD+ and FAD

• 2-carbon acetyl + 4-carbon and 2 CO2 molecules• At the same time oxaloacetic acid 6-carbon citric acid

• Oxidation and decarboxylation reactions:– Catabolize the 6-carbon citric acid back into a 4-carbon

oxaloacetic acid – 3 NAD+ and 1 FAD are reduced into 3 NADH and 1 FADH2

– 1 ATP is produced by substrate level phosphorylation

The TCA Cycle

Figure 25–4b

Citric Acid Cycle

• Remember: – 1 glucose 2 pyruvic acid

2 acetyl so this cycle will run twice

2Acetyl Co A + 6NAD+ + 2FAD + 2ADP +

2P + 4H20

2CoA + 4CO2 + 6NADH + 4H+ +

2FADH2 + 2ATP

Oxidative Phosphorylation

Figure 25–5a (Navigator)

Oxidative Phosphorylation

Figure 25–5b

Occurs on a membrane, the mitochondrial cristae, to generate most of the ATP produced from glucose

Oxidative Phosphorylation

• Is the most important mechanism for generation of ATP within the mitochondria– Produces more than 90% of ATP used by body

• Requires oxygen, electrons, and coenzymes:– rate of ATP generation is limited by oxygen or

electrons

• Cells obtain oxygen by diffusion from extracellular fluid

• Results in 2 H2 + O2 2 H2O

The Electron Transport System (ETS)

• Key reaction in oxidative phosphorylation

• Is in inner mitochondrial membrane

• Coenzymes from the previous reactions pass electrons (which transfer energy) to a series of electron carrier molecules– Molecules carry out redox reactions resulting

in the chemiosmotic generation of ATP

The Electron Transport System (ETS)

• Three classes of carrier molecules1. FMN (flavin mononucleotide): protein +

flavin coenzyme

2. Coenzyme Q: nonprotein

3. Cytochromes: protein + an iron group - Most common

Events of the Electron Transport Chain

1. NAD+ and FAD collected energy in the form of hydrogens (electrons) from organic molecules during Glycolysis, Decarboxylation, and the Citric Acid Cycle becoming that reduced forms NADH and FADH2

NAD+ + FAD NADH + FADH2

2. NADH and FADH2 are oxidized and pass hydrogens (electrons and protons) to the electron transport chain consisting of flavoproteins, cytochromes, and coenzyme Q.

NADH + FADH2 NAD+ + FAD As electrons are passed along the chain, protons are

pushed out through the membrane. This sets up a concentration gradient with protons (+ charge) on the outside and electrons (- charge) on the inside

Events of the Electron Transport Chain3. At the end of the chain the electrons are accepted by oxygen

creating an anion (O-) inside, which has a strong affinity for the cations (H+) outside.

4. Chemiosmosis generates ATP: - H+ from the outside moves toward O- on the inside through special membrane channels that are coupled to ATP synthase

- High-energy diffusion of H+ drives the reaction ADP + P ATP. a. Energy from 1 NADH from glycolysis generate 2 ATP

b. Energy from 1 NADH from decarboxylation and the citric acid cycle generate 3 ATP

c. Energy from 1 FADH2 generate 2 ATP for a total of 32 ATP5. H+ combines with O- inside the mitochondria creating water

(H2O)

Oxidative Phosphorylation

Figure 25–5b

Occurs on a membrane, the mitochondrial cristae, to generate most of the ATP produced from glucose

Summary of Electron Transport

2 NADH from glycolysis + 2 NADH from decarboxylation + 6 NADH from Citric Acid Cycle + 2 FADH2 from Citric Acid Cycle + 6 O2 + 32 ATP + 32 P

12 H2O + 32 ATP + 10 NAD+ + 2 FAD

Final Summary of Aerobic Respiration

C6H12O6 + 6 O2 + 36 ADP + 36 P

6 CO2 + 6 H2O + 36 ATP

36 ATP:2 from Glycolysis in cytoplasm2 from Citric Acid Cycle by substrate level

phosphorylation in matrix of mitochondria32 from Electron Transport by oxidative

phosphorylation in the cristae of the mitochondria

Energy Yield of Aerobic Metabolism

Figure 25–6

Lipid Catabolism: Beta–Oxidation

Figure 25–8 (Navigator)

Lipolysis – Lipid Catabolism• Hydrolyzes triglycerides (fat storage) glycerol and three fatty acids• Glycerol:

– Glycerol pyruvic acids in the cytoplasm– Pyruvic acid catabolized through TCA in mitochondria

• Fatty Acids:– Fatty acids are catabolized by beta-oxidation into acetyl-CoA – In mitochondria to enter the TCA as two-carbon fragments– For each two-carbon fragment of fatty acid produced by

beta-oxidation, the cell can generate 17 molecules of ATP• This is 1.5 times the energy production as with

glucose• Generates more energy but requires more oxygen

– Occurs much more slowly than equal carbohydrate metabolism

Amino Acid Catabolism

Figure 25–10 (Navigator)

Protein and Amino Acid Catabolism

1. Protein amino acids2. Amino group (-NH2) is removed from amino acid

in process called deamination– Requires vitamin B6

3. Amino group is removed with conjunction with a hydrogen creating ammonia (NH3)– Toxic

4. Liver converts the NH3 urea– Harmless and excreted by the kidney

5. Remaining amino acid carbon chains are used at various stages in the Citric Acid Cycle to generate ATP– Amount of ATP produced varies

Protein and Amino Acid Catabolism

• Not a Practical Source of Quick Energy • Typically only used in starvation situations• Harder to break apart than carbohydrates or

lipids• Proteins are structural and functional parts of

every cell– Thus tend to only be used when no other energy

source is available• Amino acids are simply recycled by hydrolysis of

peptide bonds in one protein, to be reassembled by dehydration synthesis into the next.

Nucleic Acid Catabolism• DNA is never catabolized for energy• RNA can be broken down into:

– Simple sugars– Nitrogenous bases

• Sugars:– Metabolized in glycolysis but only the pyrimidine bases

(uracil and cytosine) can be processed in the TCA cycle• Purines (adenine and guanine) are deaminated and excreted as uric

acid making RNA metabolism very inefficient

• Typically nucleotides are simply recycled into new nucleic acid molecules and are not used for energy production

Pathways of Catabolism and Anabolism

Figure 25–12

What is the primary role of the TCA cycle in the production of

ATP?

A. break down glucose

B. create hydrogen gradient

C. phosphorylate ADP

D. transfer electrons from substrates to coenzymes

How would a decrease in the level of cytoplasmic NAD affect ATP production in mitochondria?

A. ATP production would increase.

B. ATP production would decrease.

C. ATP production would fluctuate randomly.

D. ATP is not produced in mitochondria.

How would a diet that is deficient in pyridoxine (vitamin B6) affect protein

metabolism?

A. It would interfere with protein metabolism.

B. It would enhance protein metabolism.

C. It would cause the use of different coenzymes.

D. Pyridoxine is not involved in protein metabolism.

Elevated levels of uric acid in the blood can be an indicator of

increased metabolism of which organic compound?

A. nucleic acids

B. proteins

C. carbohydrates

D. lipids

SUMMARY

• Cellular metabolism• Catabolism and Anabolism• Carbohydrate metabolism• Glycolysis• Cellular Respiration• Mitochondrial ATP production• Lipid catabolism (Beta-oxidation)• Amino acid catabolism• Protein synthesis