How cells Make ATP: Energy Releasing

Pathways

Metabolism

• Metabolism has two complementary components:• catabolism, which releases energy by splitting complex

molecules into smaller components• anabolism, the synthesis of complex molecules from

simpler building blocks

• Most anabolic reactions are endergonic and require ATP or some other energy source to drive them

Cellular Respiration

• Every organism extracts energy from food molecules that it manufactures by photosynthesis or obtains from the environment

• Exergonic metabolic pathways (cellular respiration and fermentation) release free energy that is captured by the cell

• cellular respiration • Catabolic processes that convert energy in the chemical

bonds of nutrients to chemical energy stored in ATP• May be either aerobic or anaerobic

Aerobic Respiration

• Cells use aerobic respiration to obtain energy from glucose

C6H12O6 + 6 O2 + 6 H2O →

6 CO2 + 12 H2O + energy (chemical bonds of ATP)

• aerobic respiration

• Cellular respiration that requires molecular oxygen (O2)

• Nutrients are catabolized to carbon dioxide and water

Aerobic Respiration (cont.)

• Aerobic respiration is a redox reaction in which glucose becomes oxidized and oxygen becomes reduced

• Aerobic respiration transfers electrons (associated with hydrogen atoms in glucose) to oxygen in a series of steps that control the amount of energy released

• Free energy of the electrons is coupled to ATP synthesis• Aerobic respiration is an exergonic redox process in which

glucose becomes oxidized, oxygen becomes reduced, and energy is captured to make ATP

The Four Stages of Aerobic Respiration

Summary of Aerobic Respiration

Table 8-1, p. 174

Reactions Involved in Aerobic Respiration

• dehydrogenations• Reactions in which two hydrogen atoms are removed from

the substrate and transferred to NAD+ or FAD

• decarboxylations • Reactions in which part of a carboxyl group (COOH) is

removed from the substrate as a molecule of CO2

• Other reactions• Reactions in which molecules are rearranged so they can

undergo further dehydrogenations or decarboxylations

Introduction to Glycolysis

• Glycolysis • Takes place in the cytosol• Metabolizes the 6-carbon sugar glucose into two 3-carbon

molecules of pyruvate• Does not require oxygen; proceeds under aerobic or

anaerobic conditions• Net yield: 2 ATP molecules and 2 NADH molecules

• Two major phases:• Endergonic reactions that require ATP (investment phase)• Exergonic reactions that yield ATP and NADH (payoff

phase)

Fig. 8-3, p. 176

GLYCOLYSIS

Energy investment phase and splitting of

glucose Two ATPs invested per glucose

Glucose

3 steps

Fructose-1,6-bisphosphate

Glyceraldehyde phosphate (G3P)

Glyceraldehyde phosphate (G3P)

Energy capture phase Four ATPs

and two NADH produced per

glucose

(G3P) (G3P)

5 steps

Pyruvate Pyruvate

Net yield per glucose: Two ATPs and two NADH

First Phase of Glycolysis

• Phosphate groups are transferred from ATP to glucose In two separate phosphorylation reactions

• The phosphorylated sugar (fructose-1,6-bisphosphate) is broken enzymatically into two three-carbon molecules, yielding 2 glyceraldehyde-3-phosphate (G3P)

glucose + 2 ATP → 2 G3P + 2 ADP

Second Phase of Glycolysis

• G3P is converted to pyruvate• G3P is oxidized by removal of 2 electrons (as hydrogen

atoms), which combine with NAD+

NAD+ + 2 H → NADH + H+

• ATP is formed by substrate-level phosphorylation

2 G3P + 2 NAD+ + 4 ADP → 2 pyruvate + 2 NADH + 4 ATP

Fig. 8-4a (1), p. 178

Energy investment phase and splitting of glucose Two ATPs invested per glucose

Glucose

Hexokinase

Glucose-6-phosphate

Phosphoglucoisomerase

1

Fig. 8-4a (2), p. 178

Fructose-6-phosphate

Phosphofructokinase

Fructose-1,6-bisphosphate

Aldolase

Isomerase

Dihydroxyacetone phosphate

Glyceraldehyde- 3-phosphate (G3P)

2

3

4

5

Fig. 8-4b (1), p. 179

Two glyceraldehyde-3-phosphate (G3P) from bottom of

previous pageEnergy capture phase Four ATPs

and two NADH produced per glucose

Glyceraldehyde-3-phosphate dehydrogenase

Two 1,3-bisphosphoglycerate

Phosphoglycerokinase

Two 3-phosphoglycerate

Phosphoglyceromutase

6

7

Fig. 8-4b (2), p. 179

Two 2-phosphoglycerate

Enolase

Two phosphoenolpyruvate

Pyruvate kinase

Two pyruvate

8

9

10

Pyruvate is Converted to Acetyl CoA

• Pyruvate undergoes oxidative decarboxylation

• A carboxyl group is removed as CO2, which diffuses out of the cell

• Occurs in mitochondria of eukaryotes

• The two-carbon fragment is oxidized (NAD+ accepts the electrons), and is attached to coenzyme A, yielding acetyl coenzyme A (acetyl CoA)

2 pyruvate + 2 NAD+ + 2 CoA →

2 acetyl CoA + 2 NADH + 2 CO2

Formation of Acetyl CoA

Overview of the Citric Acid Cycle

• The citric acid cycle is also known as the Krebs cycle• Takes place in the matrix of the mitochondria• A specific enzyme catalyzes each of the eight steps• Begins when acetyl CoA transfers its two-carbon acetyl

group to the four-carbon acceptor compound oxaloacetate, forming citrate, a six-carbon compound:

oxaloacetate + acetyl CoA → citrate + CoA

The Citric Acid Cycle (cont.)

• Citrate goes through a series of chemical transformations, losing two carboxyl group as CO2

• One ATP is formed (per acetyl group) by substrate-level phosphorylation – most of the oxidative energy (in electrons) is transferred to NAD+, forming 3 NADH

• Electrons are also transferred to FAD, forming FADH2

Overview of the Citric Acid Cycle

Introduction to the Electron Transport Chain

• All electrons removed from a glucose during glycolysis, acetyl CoA formation, and the citric acid cycle are transferred as part of hydrogen atoms to NADH and FADH2

• NADH and FADH2 enter the electron transport chain (ETC), where electrons move from one acceptor to another

• Some electron energy is used to drive synthesis of ATP by oxidative phosphorylation

Transfer of Electrons

• In eukaryotes, the ETC is a series of electron carriers embedded in the inner mitochondrial membrane

• Electrons pass down the ETC in a series of redox reactions, losing some of their energy at each step along the chain

Transfer of Electrons (cont.)

• Cytochrome c reduces O2, forming H2O

• Oxygen is the final electron acceptor in the ETC

• Lack of oxygen blocks the entire ETC – no additional ATP is produced by oxidative phosphorylation

• Some poisons also inhibit normal activity of cytochromes• Example: Cyanide binds to iron in cytochrome, blocking

ATP production

Overview of the Electron Transport Chain

The Chemiosmotic Modelof ATP Synthesis

• 1961: Peter Mitchell proposed that electron transport and ATP synthesis are coupled by a proton gradient across the inner mitochondrial membrane in eukaryotes (chemiosmosis)

• Mitchell’s experiments used a bacterial model: • Bacterial cells placed in an environment with a high

hydrogen ion (proton) concentration synthesized ATP even if electron transport was not taking place

KEY EXPERIMENT:Evidence for Chemiosmosis

Plasma membrane

Fig. 8-9, p. 183

Bacterial cytoplasm (low acid)

Synthesized

Acidic environment

The Proton Gradient

• As electrons pass down the ETC, energy is used to move protons (H+) across the inner mitochondrial membrane into the intermembrane space

• The intermembrane space has a higher concentration of protons; the mitochondrial matrix has a lower concentration

• The resulting proton gradient is a form of potential energy that provides energy for ATP synthesis

Fig. 8-10, p. 184

Outer mitochondrial membrane

Inner mitochondrial membrane

Intermembrane space—low pH

Cytosol

Matrix—higher pH

The Proton

Gradient

Synthesis of ATP

• Protons diffuse from the intermembrane space (high concentration) to the matrix (low concentration) through the enzyme complex ATP synthase

• A central structure of ATP synthase rotates, catalyzing the phosphorylation of ADP to form ATP

• Chemiosmosis allows exergonic redox reactions to drive the endergonic reaction in which ATP is produced by oxidative phosphorylation

Fig. 8-11a, p. 185

Cytosol

Outer mitochondrial membrane

Outer mitochondrial membrane

Intermembrane space

Complex V: ATP synthase

Complex IIIComplex I

Complex II

Complex IVInner

mitochondrial membrane

Inner mitochondrial

membrane

Matrix of mitochondrion

Overview of the ETC

ATP Production

• Aerobic respiration of one glucose molecule:

1. Glycolysis: glucose + 2 ATP → 2 pyruvates + 2 NADH + 4 ATPs (net profit of 2 ATPs)

2. Pyruvate conversion: 2 pyruvates → 2 acetyl CoA + 2 CO2 + 2 NADH

3. Citric acid cycle: 2 acetyl CoA → 4 CO2 + 6 NADH + 2 FADH2 + 2 ATPs

• Total = 4 ATP + 10 NADH + 2 FADH2

ATP Production (cont.)

• Oxidation of NADH in the electron transport chain yields up to 3 ATPs per molecule (10 NADH X 3 = 30 ATPs)

• Oxidation of FADH2 yields 2 ATPs per molecule

(2 FADH2 X 2 = 4 ATPs)

ATP Production (cont.)

• Summing all the ATPs:• 2 from glycolysis• 2 from the citric acid cycle• 32 to 34 from electron transport and

chemiosmosis

• Complete aerobic metabolism of one molecule of glucose yields a maximum of 36 to 38 ATPs

Energy Yield from Oxidation of Glucose by Aerobic Respiration

Cells Regulate Aerobic Respiration

• Glycolysis is partly controlled by feedback regulation of the enzyme phosphofructokinase

• Phosphofructokinase has two allosteric sites:• An inhibitor site that binds ATP (at very high ATP levels)• An activator site to which AMP binds (when ATP is low)

KEY CONCEPTS 8.2

• Aerobic respiration consists of four stages: glycolysis, formation of acetyl coenzyme A, the citric acid cycle, and the electron transport chain and chemiosmosis

Animation: Recreating the reactions of glycolysis

Nutrients Other Than Glucose

• Nutrients other than glucose are transformed into metabolic intermediates that enter glycolysis or the citric acid cycle

• Amino acids:

• The amino group (NH2) is removed (deamination)

• The carbon chain is used in aerobic respiration

• Lipids:• Glycerol is converted to a compound that enters glycolysis• Fatty acids are converted by β-oxidation to acetyl CoA,

which enters the citric acid cycle

Fig. 8-13, p. 187

PROTEINS CARBOHYDRATES FATS

Amino acids

Glycolysis Fatty acids

Glycerol

Glucose

G3P

Pyruvate

CO 2

Acetyl coenzyme

A

Citric acid cycle

Electron transport

and chemiosmosis

End products: NH3 H2O CO2

Energy from Proteins,Carbohydrates, and Fats

Anaerobic Respiration

• anaerobic respiration• Does not use oxygen as the final electron acceptor• Used by prokaryotes in anaerobic environments, such as

waterlogged soil, stagnant ponds, and animal intestines

• Electrons from glucose pass from NADH down an ETC coupled to ATP synthesis by chemiosmosis

• End products of this of anaerobic respiration are CO2, one or more reduced inorganic substances, and ATP

Fermentation

• fermentation• An anaerobic pathway that does not involve an ETC• Only two ATPs are formed per glucose (by substrate-level

phosphorylation during glycolysis)• NADH molecules transfer H atoms to organic molecules,

regenerating NAD+ needed for glycolysis

• Fermentation is highly inefficient, because fuel is only partially oxidized

Alcohol Fermentation

• Yeasts are facultative anaerobes that carry out aerobic respiration when oxygen is available but switch to alcohol fermentation when deprived of oxygen

• alcohol fermentation• Enzymes decarboxylate pyruvate, forming acetaldehyde• NADH produced during glycolysis transfers hydrogen

atoms to acetaldehyde, reducing it to ethyl alcohol

Lactate Fermentation

• Certain fungi bacteria perform lactate fermentation – vertebrate muscle cells also produce lactate when oxygen is depleted during exercise

• lactate (lactic acid) fermentation• NADH produced during glycolysis transfers hydrogen

atoms to pyruvate, reducing it to lactate

Fermentation

Aerobic Respiration, Anaerobic Respiration, and Fermentation

Table 8-2, p. 188