Chapter 23

Metabolism and Energy production

Chemistry 203

Metabolism

Chemical reactions in cells that break down or build molecules. It produces energy and provide substances to cell growth.

Catabolic reactions:

Anabolic reactions:

Complex molecules Simple molecules + Energy

Simple molecules + Energy (in cell) Complex molecules

The sum of all the chemical reactions that take place in an organism.

Metabolic Pathway

A series of consecutive reactions.

A linear pathway is the series of reactions that generates a final product different from any of the reactants.

A cyclic pathway is the series of reactions that regenerates the first reactant.

Metabolism in cell

CarbohydratesPolysaccharides

Proteins

Lipids

GlucoseFructose

Galactose

Amino acids

Glycerol

Fatty acids

Stage 1: Digestion and hydrolysis

Glucose Pyruvate Acetyl CoACitricAcidcycle

CO2 & H2O

UreaNH4

+

Stage 2: Degradationand some oxidation

Stage 3: Oxidation to CO2,H2O and energy

e

e

Mitochondria

(Formation of Acetyl CoA)

Cell Structure

Membrane

Nucleus

Cytoplasm

(Cytosol)

Mitochondria

Nucleus: consists the genes that control DNA replication and protein synthesis of the cell.

Cytoplasm: consists all the materials between nucleus and cell membrane.

Cytosol: fluid part of the cytoplasm (electrolytes and enzymes).

Organelles: the specialized structures within cells (carry out specific functions).

Mitochondria: energy producing factories.

Cell Structure

Enzymes in matrix catalyze the oxidation of carbohydrates, fats , and amino acids.

Produce CO2, H2O, and energy.

ATP and Energy

- Adenosine triphosphate (ATP) is produced from the oxidation of food.

- Has a high energy.

- Can be hydrolyzed and produce energy.

ATP and Energy

-O-P-O-P-O-AMPO

O--O

OH2O

ATP ADP

-O-P-O-AMP-O

OH2PO4

-+ + + 7.3 kcal/mol

Pi

(adenosine triphosphate) (adenosine diphosphate) (inorganic phosphate)

- We use this energy for muscle contraction, synthesis an enzyme, send nerve signal, and transport of substances across the cell membrane.

- 1-2 million ATP molecules may be hydrolysis in one second (1 gram in our cells).

- When we eat food, catabolic reactions provide energy to recreate ATP.

ADP + Pi + 7.3 kcal/mol ATP

Phosphorylation is the reverse reaction, where a phosphate group is added to ADP.

Coupled Reactions

Coupled reactions are pairs of reactions that occur together.

The energy released by one reaction is absorbed by the other reaction.

ATP + H2O ∆H = −7.3 kcal/mol

energy is released

ADP + HPO42- ∆H = +7.3 kcal/mol

energy is absorbed

ADP + HPO42−

ATP + H2O

Exothermic: a favorable reaction

Endothermic: an unfavorable reaction

Coupled Reactions

The hydrolysis of ATP provides the energy for the phosphorylation of glucose.

Coupling an energetically unfavorable reaction with a favorable one that releases more energy than the amount required is common in biological reactions.

Stage 1: Digestion

Carbohydrates Lipids (fat) Proteins

Convert large molecules to smaller ones

that can be absorbed by the body.

Digestion: Carbohydrates

+

+

Polysaccharides

Dextrins

Maltose Glucose

Mouth

Salivaryamylase

Stomach pH = 2 (acidic)

Maltose +Maltase

Glucose Glucose

Lactose +Lactase

Galactose Glucose

Sucrose +Sucrase

Fructose Glucose

Small intestinepH = 8

Dextrins

Bloodstream Liver (convert all to glucose)

α-amylase (pancreas)

Digestion: Lipids (fat)

Intestinal wall

Monoacylglycerols + 2 Fatty acids → Triacylglycerols

Small intestine

Bloodstream

Glycerol + 3 Fatty acids

H2C

HC

H2C

Fatty acid

Fatty acid

Fatty acid

+ 2H2O

H2C

HC

H2C

OH

Fatty acid

OH

+ 2 Fatty acids

lipase(pancreas)

Triacylglycerol Monoacylglycerol

Protein

Lipoproteins

Chylomicrons

Lymphatic system

Cells Enzymes hydrolyzes

liver Glucose

Digestion: Proteins

Intestinal wall

Small intestine

Bloodstream

Cells

Stomach

Pepsinogen Pepsin

Proteins Polypeptides

HCl

Polypeptides Amino acids

TypsinChymotrypsin

denaturation + hydrolysis

hydrolysis

Some important coenzymes

2 H atoms 2H+ + 2e-

oxidation Coenzyme + Substrate Coenzyme(+2H) + Substrate(-2H)

Reduced Oxidized

NAD+

FAD

Coenzyme A

Coenzymes

NAD+

Nicotinamide adenine dinucleotide

HH

H

O

HO OH

N

CNH2

-O-P-O-CH2

O

O

AMP H

O

a -N-glycosidic bond

+

The plus sign on NAD+

represents the positivecharge on this nitrogen

Nicotinamide;derivedfrom niacin

ADP

(vitamin)

Ribose

(Vitamin B3)

fish, nuts

- Is an oxidizing agent.

- Participates in reactions that produce (C=O) such as oxidation of alcohols to aldehydes and ketones.

NAD+

CH3-CH2-OH + NAD+ CH3-C-H + NADH + H+

NAD+ + 2H+ + 2e- NADH + H+

NAd

CNH2

OH

H+ 2e-

NAd

CNH2

OH H

+ +

NAD+

(oxidized form)NADH

(reduced form)

:+

O

Reduced

FAD

Flavin adenine dinucleotide

O=P-O-AMP

O-

CH2

C

O

C

C

CH2

N

H OH

OHH

H

N

N

NH3C

H3C O

HO

OH Ribitol

Flavin

Riboflavin

ADP

(Vitamin B2)

(sugar alcohol)Soybeans, almonds, liver

FAD

- Is an oxidizing agent.

- Participates in reaction that produce (C=C) such as dehydrogenation of alkanes.

R-C-C-R + FAD R-C=C-H + FADH2

H H

H H H H

AdN

N

N

NHH3C

H3C O

O

+ 2H+ + 2e-H3C

H3C O

OH

HAdN

N

N

NH

FAD FADH2

Reduced

Coenzyme A (CoA)

Aminoethanethiol

( vitamin B5)

Coenzyme A

whole grain, egg

Coenzyme A (CoA)

CH3-C- + HS-CoA CH3-C-S-CoA

O O

Acetyl group Coenzyme A Acetyl CoA

- It activates acyl groups (RC-), particularly the Acetyl group (CH3C-).

When the thioester bond is broken, 7.5 kcal/mol of energy is released.

R-C-S-R’

O

A Thioester

O O

Metabolism in cell

CarbohydratesPolysaccharides

Proteins

Lipids

GlucoseFructose

Galactose

Amino acids

Glycerol

Fatty acids

Stage 1: Digestion and hydrolysis

Glucose Pyruvate Acetyl CoACitricAcidcycle

CO2 & H2O

UreaNH4

+

Stage 2: Degradationand some oxidation

Stage 3: Oxidation to CO2,H2O and energy

e

e

Mitochondria

(Formation of Acetyl CoA)

- We obtain most of our energy from glucose.

- Glucose is produced when we digest the carbohydrates in our food.

- We do not need oxygen in glycolysis (anaerobic process).

C6H12O6 + 2 NAD+ 2CH3-C-COO- + 2 NADH + 4H+

O

PyruvateGlucose

2 ADP + 2Pi 2 ATP

Glycolysis: Oxidation of glucose

Stage 2: Formation of Acetyl CoA

Inside of cell (Cytoplasm)

Pathways for pyruvate

Aerobic conditions: if we have enough oxygen.

Anaerobic conditions: if we do not have enough oxygen.

- Pyruvate can produce more energy.

Aerobic conditions

- Pyruvate is oxidized and a C atom remove (CO2).

- Acetyl is attached to coenzyme A (CoA).

- Coenzyme NAD+ is required for oxidation.

CH3-C-C-O- + HS-CoA + NAD+ CH3-C-S-CoA + CO2 + NADH

O O

pyruvate Coenzyme A Acetyl CoA

O

Important intermediate productin metabolism.

Anaerobic conditions

- When we exercise, the O2 stored in our muscle cells is used.

- Pyruvate is reduced to lactate.

- Accumulation of lactate causes the muscles to tire and sore.

- Then we breathe rapidly to repay the O2.

- Most lactate is transported to liver to convert back into pyruvate.

CH3-C-C-O- CH3-C-C-O-

O O

pyruvate Lactate

O HO

H

Reduced

NADH + H+ NAD+

Glycogen

- If we get excess glucose (from our diet), glucose convert to glycogen.

- It is stored in muscle and liver.

- We can use it later to convert into glucose and then energy.

- When glycogen stores are full, glucose is converted to triacylglycerols and stored as body fat.

Metabolism in cell

CarbohydratesPolysaccharides

Proteins

Lipids

GlucoseFructose

Galactose

Amino acids

Glycerol

Fatty acids

Stage 1: Digestion and hydrolysis

Glucose Pyruvate Acetyl CoACitricAcidcycle

CO2 & H2O

UreaNH4

+

Stage 2: Degradationand some oxidation

Stage 3: Oxidation to CO2,H2O and energy

e

e

Mitochondria

(Formation of Acetyl CoA)

Stage 3: Citric Acid Cycle (Kerbs Cycle)

- Is a central pathway in metabolism.

- Uses acetyl CoA from the degradation of carbohydrates, lipids, and proteins.

- Two CO2 are given off.

- There are four oxidation steps in the cycle provide H+ and electrons to reduce FAD and NAD+ (FADH2 and NADH).

8 reactions

Reaction 1

Formation of Citrate

CH3-C-S-CoA

O

Acetyl CoA

COO-

C=O

CH2

COO-

Oxaloacetate

COO-

CH2

CH2

COO-

CHO COO-

Citrate

+ CoA-SH

Coenzyme A

+

H2O

CitrateSynthase

Reaction 2

Isomerisation to Isocitrate

COO-

CH2

CH2

COO-

CHO COO-

Citrate Isocitrate

COO-

CH2

C

COO-

CH COO-

HO H

Isomerization

- Because the tertiary –OH cannot be oxidized. (convert to secondary –OH)

Aconitase

Reaction 3

First oxidative decarboxylation (CO2)

Isocitrate

COO-

CH2

C

COO-

CH COO-

HO H

- Oxidation (-OH converts to C=O).- NAD+ is reduced to NADH.- A carboxylate group (-COO-) is removed (CO2).

C-COO-H

CH-COO-

CH2-COO-

HOIsocitrate

C-COO-H

C-COO-

CH2-COO-

C-HH

C-COO-

CH2-COO-

NADH + H+NAD+

-Ketoglutarate

CO2

isocitratedehydrogenase

O O

Oxalosuccinate

COO-

CH2

C

COO-

CH COO-

O

α-Ketoglutrate

COO-

CH2

C

COO-

CH2

O+ CO2

Isocitratedehydrogenase

H+

Reaction 4

Second oxidative decarboxylation (CO2)

α-Ketoglutrate

COO-

CH2

C

COO-

CH2

O CH2

C-COO-

CH2-COO-

-Ketoglutarate

O

CoA-SH

NADHNAD+

-ketoglutaratedehydrogenase

complex

CH2

C

CH2-COO-

SCoAOSuccinyl-CoA

+ CO2

Succinyl CoA

COO-

CH2

C

S-CoA

CH2

O + CO2

- Coenzyme A convert to succinyl CoA.- NAD+ is reduced to NADH.- A second carboxylate group (-COO-) is removed (CO2).

α-Ketoglutratedehydrogenase

(a Thioester)

Reaction 5

Hydrolysis of Succinyl CoA

Succinyl CoA

COO-

CH2

C

S-CoA

CH2

O

- Energy from hydrolysis of succinyl CoA is used to add a phosphate group (Pi) to GDP (guanosine diphosphate).

- The hydrolysis of GTP is used to add a Pi to ADP to produce ATP.

+ H2O + GDP + Pi

COO-

CH2

CH2

COO-

Succinate

+ GTP + CoA-SH

GTP + ADP → GDP+ ATP

Reaction 6

Dehydrogenation of Succinate

- H is removed from two carbon atoms.- Double bond is produced.- FAD is reduced to FADH2.

COO-

CH2

CH2

COO-

Succinate

FAD FADH2

CH2-COO-

CH2-COO-

Succinate

succinatedehydrogenase

C

CH

H

COO-

-OOC

Fumarate

COO-

CH

CH

COO-

Fumarate

Succinatedehydrogenase

Reaction 7

Hydration

- Water adds to double bond of fumarate to produce malate.

COO-

C

CH2

COO-

HO H

Malate

H2O

COO-

CH

CH

COO-

Fumarate

Reaction 8

Dehydrogenation forms oxaloacetate

- -OH group in malate is oxidized to oxaloacetate.

- Coenzyme NAD+ is reduced to NADH + H+.

COO-

C

CH2

COO-

HO H

Malate

COO-

C=O

CH2

COO-

Oxaloacetate

C-COO-

CH2-COO-

Oxaloacetate

NAD+ NADH

malatedehydrogenase

CH-COO-HO

CH2-COO-

L-Malate

O+ H+

The product of step [8] is the starting material for step [1].

Summary

The catabolism of proteins, carbohydrates, and fatty acids

all feed into the citric acid cycle at one or more points:

Citric AcidCycle

Summary

Summary

The main function of the citric acid cycle is to produce reduced coenzymes (NADH and FADH2).

Summary

These molecules enter the electron transport chain (Stage 4) and ultimately produce ATP.

Feedback Mechanism

The rate of the citric acid cycle depends on the body’s need for energy.

When energy demands are high and ATP is low → the cycle is activated.

When energy demands are low and NADH is high → the cycle is inhibited.

Stage 4: Electron Transport & Oxidative Phosphorylation

- Most of energy generated during this stage.

- It is an aerobic respiration (O2 is required).

1. Electron Transport Chain (Respiratory Chain)

2. Oxidative Phosphorylation

Stage 4: Electron Transport Chain

H+ and electrons from NADH and FADH2 are carried by an electron carrieruntil they combine with oxygen to form H2O.

FMN (Flavin Mononucleotide)

Fe-S clusters

Coenzyme Q (CoQ)

Cytochrome (cyt)

Electron carriers

FMN (Flavin Mononucleotide)

O=P-O-AMP

O-

CH2

C

O

C

C

CH2

N

H OH

OHH

H

N

N

NH3C

H3C O

HO

OH Ribitol

Flavin

Riboflavin

(Vitamin B2)

(sugar alcohol)

-

2H+ + 2e-

O=P-O-AMP

O-

CH2

C

O

C

C

CH2

N

H OH

OHH

H

N

N

NH3C

H3C O

HO

OH Ribitol

Flavin

Riboflavin

-

H

H

FMN + 2H+ + 2e- → FMNH2

Reduced

Fe-S Clusters

Fe3+

SS

SS

Cys

Cys

Cys

Cys

Fe2+

SS

SS

Cys

Cys

Cys

Cys

+ 1 e-

Fe3+ + 1e- Fe2+

Reduced

Coenzyme Q (CoQ)

OH

OH

2H+ + 2e-

Reduced Coenzyme Q (QH2)Coenzyme Q

Q + 2H+ + 2e- → QH2

Reduced

Cytochromes (cyt)

- They contain an iron ion (Fe3+) in a heme group.

- They accept an electron and reduce to (Fe2+).

- They pass the electron to the next cytochrome and they are oxidized back to Fe3+.

Fe3+ + 1e- Fe2+

ReducedOxidized

cyt b, cyt c1, cyt c, cyt a, cyt a3

Electron Transport Chain

Mitochondria

4 enzyme complexes (I, II, III and IV)

Complex I

NADH + H+ + FMN → NAD+ + FMNH2

FMNH2 + Q → QH2 + FMN

NADH + H+ + Q → QH2 + NAD+

Complex II

FADH2 + Q → FAD + QH2

Electron Transport Chain

Oxidized

Oxidized

Complex III

QH2 + 2 cyt b (Fe3+) → Q + 2 cyt b (Fe2+) + 2H+

Complex IV

4H+ + 4e- + O2 → 2H2O

Electron Transport Chain

Aerobic

From the electrontransport chain

From inhaled airFrom reduced coenzymes

or the matrix

Chemiosmotic model

- H+ make inner mitochondria acidic.- Produces different proton gradient. - H+ pass through ATP synthase (a protein complex).

ATP synthase

Stage 4: Oxidative Phosphorylation

Transport of electrons produce energy to convert ADP to ATP.

ADP + HPO42- + Energy → ATP + H2O

Energy released from oxidation of The reduced coenzymes fuels phosphorylation

Total ATP

Each NADH entering the electron transport chain produces enough energy to make 2.5 ATPs.

Each FADH2 entering the electron transport chain produces enough energy to make 1.5 ATPs.

The citric acid cycle produces overall:

3 NADH x 2.5 ATP = 7.5 ATP

1 FADH2 x 1.5 ATP = 1.5 ATP

1 GTP = 1 ATP

10 ATP From each Acetyl CoA

(Reaction 5)

Total ATP

Glycolysis: 7 ATP

Oxidation of Pyruvate: 5 ATP

Citric acid cycle: 20 ATP

32 ATPOxidation of glucose

C6H12O6 + 6O2 + 32 ADP + 32 Pi → 6CO2 + 6H2O + 32 ATP

Metabolism in cell

CarbohydratesPolysaccharides

Proteins

Lipids

GlucoseFructose

Galactose

Amino acids

Glycerol

Fatty acids

Stage 1: Digestion and hydrolysis

Glucose Pyruvate Acetyl CoACitricAcidcycle

CO2 & H2O

UreaNH4

+

Stage 2: Degradationand some oxidation

Stage 3: Oxidation to CO2,H2O and energy

e

e

Mitochondria

(Formation of Acetyl CoA)

Oxidation of fatty acids

CH3-(CH2)14-CH2-CH2-C-OH

O α

oxidation

- Oxidation happens in step 2 and 3.

- Each beta oxidation produces acetyl CoA and a shorter fatty acid.

- Oxidation continues until fatty acid is completely break down to acytel CoA.

Oxidation of fatty acids

Fatty acid activation

- Before oxidation, they activate in cytosol.

R-CH2-C-OH

O

+ ATP + HS-CoA R-CH2-C-S-CoA

O

+ H2O + AMP + 2Pi

Fatty acyl CoAFatty acid

-Oxidation: 4 reactions

Reaction 1: Oxidation (dehydrogenation)

R-CH2-C-C-C-S-CoA

O

Fatty acyl CoA

H H

H H

+ FAD R-CH2-C=C-C-S-CoA + FADH2

OH

H

Reaction 2: Hydration

R-CH2-C=C-C-S-CoA + H2O

OH

H

R-CH2-C-C-C-S-CoA

O

H H

HHO

Reaction 3: Oxidation (dehydrogenation)

Reaction 4: Cleavage of Acetyl CoA

R-CH2-C-C-C-S-CoA + NAD+

O

H H

HHO

R-CH2-C-CH2-C-S-CoA + NADH+ H+

OO

R-CH2-C-CH2-C-S-CoA + CoA-SH

OO

R-CH2-C-S-CoA

O

CH3-C-S-CoA

O

+

Acetyl CoAFatty acyl CoA

Oxidation of fatty acids

One cycle of -oxidation

R-CH2-CH2-C-S-CoA + NAD+ + FAD + H2O + CoA-SH

O

R-C-S-CoA

O

CH3-C-S-CoA + NADH + H+ + FADH2

O

+

Acetyl CoAFatty acyl CoA

# of Acetyl CoA =# of fatty acid carbon

2= 1 + oxidation cycles

Ketone bodies

- If carbohydrates are not available to produce energy.

- Body breaks down body fat to fatty acids and then Acetyl CoA.

- Acetyl CoA combine together to produce ketone bodies.

- They are produced in liver.

- They are transported to cells (heart, brain, or muscle).

CH3-C-S-CoA

O

Acetyl CoA

CH3-C-S-CoA

OCH3-C-CH2-C-O-

O O CH3-C-CH3 + CO2 + energy

O

Acetoacetate

Acetone

-Hydroxybutyrate

CH3-CH-CH2-C-O-

OH O

Ketosis (disease)

- When ketone bodies accumulate and they cannot be metabolized.

- Found in diabetes and in high diet in fat and low in carbohydrates.

- They can lower the blood pH (acidosis).

- Blood cannot carry oxygen and cause breathing difficulties.

Fatty acid synthesis

- When glycogen store is full (no more energy need).

- Excess acetyl CoA convert to 16-C fatty acid (palmitic acid) in cytosol.

- New fatty acids are attached to glycerol to make triacylglycerols. (are stored as body fat)

Metabolism in cell

CarbohydratesPolysaccharides

Proteins

Lipids

GlucoseFructose

Galactose

Amino acids

Glycerol

Fatty acids

Stage 1: Digestion and hydrolysis

Glucose Pyruvate Acetyl CoACitricAcidcycle

CO2 & H2O

UreaNH4

+

Stage 2: Degradationand some oxidation

Stage 3: Oxidation to CO2,H2O and energy

e

e

Mitochondria

(Formation of Acetyl CoA)

Degradation of amino acids

- They are degraded in liver.

Transamination:

- They react with α-keto acids and produce a new amino acid and a new α-keto acid.

-OOC-C-CH2-CH2-COO-

O

alanine

CH3-CH-COO-

NH3

+

+

α-ketoglutarate

-OOC-CH-CH2-CH2-COO-

O

pyruvate

CH3-C-COO-

NH3

+

+

glutamate

Degradation of amino acids

Oxidative Deamination

-OOC-CH-CH2-CH2-COO-

NH3

+

glutamate

+ H2O + NAD+

-OOC-C-CH2-CH2-COO-

O

α-ketoglutarate

glutamatedehydrogenase

+ NH4+ + NADH + H+

Urea cycle

- Ammonium ion (NH4+) is highly toxic.

- Combines with CO2 to produce urea (excreted in urine).

- If urea is not properly excreted, BUN (Blood Urea Nitrogen) level in blood becomes high and it build up a toxic level (renal disease).

- Protein intake must be reduced and hemodialysis may be needed.

H2N-C-NH2 + 2H+ + H2O

O

urea

2NH4+ + CO2

Energy from amino acids

- C from transamination are used as intermediates of the citric acid cycle.

- amino acid with 3C: pyruvate- amino acid with 4C: oxaloacetate- amino acid with 5C: α-ketoglutarate

- 10% of our energy comes from amino acids.

- But, if carbohydrates and fat stores are finished, we take energy from them.