Chapter 18 Chemistry: Metabolic Pathways and ATP Production

Metabolism

involves

• all chemical reactions that provide energy and substances needed for growth

• Catabolic reactions

• anabolic reaction

Catabolic reactions

break down large, complex molecules to provide energy and smaller molecules

Anabolic reactions

Use ATO energy to build up larger molecules

Stages of Metabolism

Catabolic reactions are organized in stages.

Stage 1: Digestion and hydrolysis

Stage 2: Degradation

Stage 3: Oxidation

Stage 1: Digestion and hydrolysis

break down large molecules to smaller ones that enter the blood stream

Stage 2: Degradation

breaks down molecules to two- and three-carbon compounds

Stage 3: Oxidation

oxidation of small molecules in the citric acid cycle and electron transport provides ATP energy

Cell membrane

Separates the contents of a cell from the external environment and contains structures that communicate with other cells

Cytoplasm

Consists of the cellular contents between the cell membrane and nucleus

Cytosol

Fluid part of the cytoplasm that contains enzymes for many of the cell’s chemical reactions

Mitochondrion

Contains the structures for the synthesis of ATP from energy-releasing reactions

Nucleus

Contains genetic information for the replication of DNA and the synthesis of protein

Ribosome

Site of protein synthesis using mRNA templates

How is energy stored in the body?

as adenosine triphosphate (ATP)

When does ATP hydrolysis happen?

Every time we contract muscles, move substances across cellular membranes, send nerve signals, or synthesize an enzyme, we use the energy from it.

Hydrolysis of ATP

The hydrolysis of ATP to ADP (adenosine diphosphate) releases 7.3 kilocalories per mole of ATP.

ATP —> ADP + P_i + 7.3 kcal/mole

Hydrolysis of ADP

ADP can also hydrolyze to form adenosine monophosphate (AMP) and an inorganic phosphate i (P)

ADP —> AMP + P_i + 7.3 kcal/mole

ATP

the energy-storage molecule, links energy-producing reactions with energy-requiring reactions in the cells

Digestion of carbohydrates in mouth

Enzymes produced in the salivary glands hydrolyze some of the a -glycosidic bonds in amylose and amylopectin, producing smaller polysaccharides such as

• maltose

• glucose

• dextrins (may contain 3-8 glucose units)

What happens after the partially digested starches are swallowed?

starches enter the acidic environment of the stomach, where the low pH stops carbohydrate digestion.

Digestion of carbohydrates in the small intestine

In the small intestine, which has a pH of about 8,

• enzymes produced in the pancreas hydrolyze the remaining dextrins to maltose and glucose

• enzymes produced in the mucosal cells that line the small intestine hydrolyze maltose as well as lactose and sucrose into monosaccharides

What happens to the monosaccharides after digestion in the small intestine?

Monosaccharides are then absorbed through the intestinal wall to the blood stream and carried to the liver, where any fructose and galactose are converted to glucose.

Digestion

Carbohydrates begin digestion in the mouth, lipids in the small intestine, and proteins in the stomach and small intestine.

Stage 1 of catabolism in carbohydrates

the digestion of carbohydrates begins in the mouth and is completed in the small intestine

Digestion of fats (triacylglycerols)

begins in the small intestine, where bile salts break fat globules into smaller particles called micelles

What happens in the digestion of triacylglycerols

The triacylglycerols are hydrolyzed in the small intestine and re-formed in the intestinal lining, where they bind to proteins for transport through the lymphatic system and bloodstream to the cells.

Digestion of proteins

• begins in the stomach, where HCl at pH 2 denatures proteins and activates enzymes such as pepsin to hydrolyze peptide bonds

• moves out of the stomach to the small intestine, where trypsin and chymotrypsin hydrolyze the polypeptides to amino acids

• ends as amino acids are absorbed through the intestinal walls and enter the bloodstream for transport to the cells

Where are proteins hydrolyzed?

in the stomach and the small intestine

Coenzymes in Metabolic Pathways

The NAD⁺ coenzyme is required for metabolic reactions that produce carbon-oxygen (C=O) double bonds, such as in the oxidation of alcohols to aldehydes and ketones.

Oxidation reactions

involve

• a loss of hydrogen

• a loss of electrons

• and increase in number of bonds to hydrogen

Reduction reactions

involve

• the gain of hydrogen ions and electrons

• a decrease in the number of bonds to oxygen

Coenzyme NAD⁺

NAD⁺ (nicotinamide adenine dinucleotide) is an important coenzyme in which the B₃ vitamin, niacin, provides the nicotinamide group, which is bonded to ADP

What does the coenzyme NAD⁺ participates in?

the reaction that produce a carbon-oxygen double bonds (C=O)

Coenzyme FAD

FAD (flavin adenine dinucleotide) is a coenzyme that

• contains ADP and riboflavin (vitamin B₂ )

• is reduced to FADH₂ when flavin accepts 2H⁺ and 2e^-

What does the coenzyme FAD participates in?

in reactions that convert a carbon–carbon single bond to a carbon–carbon double bond (C=C)

How is FAD used in the citric acid cycle?

in the conversion of the carbon–carbon single bond in succinate to a double bond in fumarate

Structure of Coenzyme A

Coenzyme A (CoA) contains pantothenic acid (vitamin B5 ) phosphorylated ADP, and aminoethanethiol.

Function of coenzyme A

• is to prepare small acyl groups (represented by the letter A in the name), such as acetyl, for reactions with enzymes.

• The thiol group ( SH) -- bonds to a two-carbon acetyl group to produce the energy-rich thioester acetyl-CoA

Glycolysis

• is a metabolic pathway that uses glucose, a digestion product from carbohydrates

• degrades six-carbon glucose molecules to three-carbon pyruvate molecules

Where does glycolysis take place?

in the cytoplasm of the cell

What kind of process is glycolysis?

is an anaerobic process: no oxygen is required

In reaction 1 to 5 of glycolysis,

• energy is required to add phosphate groups to glucose

• glucose is converted to two three-carbon molecules

In glycolysis,

• two ATP add phosphate to glucose and fructose-1,6- bisphosphate

• four ATPs are produced during phosphate transfers

• there is a net gain of two ATP and two NADH when glucose is converted to two pyruvate

Pyruvate Pathways: Aerobic and Anaerobic

Pyruvate is converted to acetyl CoA under aerobic conditions and to lactate under anaerobic conditions

The Citric Acid Cycle

is a series of reactions that connects the intermediate acetyl-CoA from the metabolic pathways in stages 1 and 2 with electron transport and the synthesis of ATP in stage 3.

citric acid cycle components

• uses the two-carbon acetyl group in acetyl CoA to produce CO₂ , NADH+ H⁺ , and FADH₂

What is the Citric Acid Cycle named after?

• the citrate ion from citric acid (CHO , 68 7 ) a tricarboxylic acid, which forms in the first reaction

• is also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle

Citric Acid Cycle process

• an acetyl group (2C) in acetyl CoA bonds to oxaloacetate (4C) to form citrate (6C)

• two decarboxylation reactions remove carbon atoms as C O2 molecules to give succinyl-CoA (4C)

• a series of reactions converts four-carbon succinyl-CoA to oxaloacetate, which combines with another acetyl-CoA, and the citric cycle starts all over

Citric Acid cycle: overall reaction

one complete citric acid cycle

Electron transport chain

hydrogen ions and electrons from NADH and FADH2 are passed from one electron carrier to the next and combine with oxygen to make H O.

What is the energy released during electron transport used for?

to synthesize ATP from ADP and P_i , a process called oxidative phosphorylation.

A mitochondrion contains

• an outer membrane, an intermembrane space, and a highly folded inner membrane that surrounds the matrix

• enzymes and electron carriers along the inner membrane required for electron transport

• four distinct protein complexes—complex I, II, III, and IV — located within these membranes

Two electron carriers, coenzyme Q and cytochrome c,

• are firmly attached to the membrane

• function as mobile carriers shuttling electrons between the protein complexes that are bound to the inner membrane

Electron carriers

Coenzymes NADH and FADH₂ are oxidized in enzyme complexes providing electrons and hydrogen ions for ATP synthesis

Oxidation phosphorylation in the chemiosmotic model

• each complex acts as a proton pump by pushing H⁺ ions from the oxidation of NADH and FADH₂ out of the matrix and into the intermembrane space

• the increase in H⁺ concentration lowers the pH and creates an H⁺ or electrochemical gradient

What is done to equalize the pH and charge in oxidative phosphorylation?

to equalize the pH and charge between the intermembrane space and the matrix, the + H ions return to the matrix by passing through a protein complex called ATP synthase

The process of oxidative phosphorylation

couples the energy from electron transport to the synthesis of ATP from ADP.

What happens to NADH during ATP synthase?

When NADH enters electron transport at complex I, the energy released from its oxidation is used to synthesize 2.5 ATP

What happens to FADH₂ during ATP synthesis?

FADH₂ enters electron transport at complex II, which is at a lower energy level. Thus, FADH₂ provides energy to produce 1.5 ATP

ATP from Glycolysis

Glycolysis yields a total of seven ATP:

• five ATP from two NADH

• two ATP from direct phosphorylation

ATP from Oxidation of two pyruvates

Under aerobic conditions,

• two pyruvate enter the mitochondria and are oxidized to two acetyl-CoA, CO₂ , and two NADH

• two NADH enter electron transport to provide five ATP

ATP from the Citric Acid Cycle

One turn of the citric acid cycle provides

3 NADH _^x 2.5 ATP/NADH = 7.5 ATP

1 FADH _^x 1.5 ATP/FADH₂ = 1.5 ATP

1 GTP _^x 1 ATP/1 GTP = 1 ATP

Total = 10 ATP

Because each glucose provides two acetyl-CoA, two turns of the citric acid cycle produce 20 ATP

The complete oxidation of glucose yield

The complete oxidation of glucose to C₂O and H₂O yields a total of 32 ATP.

Oxidation of fatty acids

A large amount of energy is obtained when fatty acids undergo oxidation in the mitochondria to yield acetyl-CoA.

Stage 2 of fat metabolism

Fatty acids undergo beta-oxidation (β - oxidation), which removes two-carbon segments, one at a time, from the carboxyl end

Each cycle in oxidation produces acetyl-CoA and a fatty acid that is shorter by two carbons

Fatty acid activation

• prepares fatty acids for transport through the inner membrane of mitochondria

• combines a fatty acid with coenzyme A to yield fatty acyl-CoA

What does fatty acid activation require?

energy obtained from hydrolysis of ATP to give AMP and 2P_i

Reactions of the β - oxidation cycle

• fatty acyl-CoA molecules undergo β oxidation, a cycle of four reactions converting the β - carbon —CH₂— to a β -keto

• once the β -keto group is formed, a two-carbon acetyl group can be split from the carbon chain, shortening the fatty acyl chain

Cycles of β -Oxidation

The number of β -oxidation cycles

• depends on the length of a fatty acid

• is one less than the number of acetyl- CoA groups formed

ATP from Fatty Acid Oxidation

In each β -oxidation cycle,

• one NADH is produced, generating 2.5 ATP

• one FADH₂ is produced, generating 1.5 ATP

• one acetyl-CoA is produced, generating 10 ATP

What happens if carbohydrates are not available?

the body breaks down to meet energy needs

• ketone bodies

How do ketone bodies form?

in a process called ketogenesis

In ketogenesis

acetyl-CoA molecules combine to produce ketone bodies: acetoacetate, β - hydroxybutyrate, and acetone

Formation of Ketone bodies

ketone bodies form

• in large amounts of acetyl-CoA accumulate

• when two acetyl-CoA molecules form acetoacetyl-CoA

• when acetoacetyl-CoA hydrolyzes to acetoacetate

• when acetoacetate reduces to β - hydroxybutyrate or loses CO2 to form acetone, both ketone bodies

When does ketosis occur

• in diabetes, diets high in fat, and starvation

• as ketone bodies accumulate

• when acidic ketone bodies lower blood pH below 7.4 (acidosis)

Leptin

hormone that is produced in fat cells

When fat stores are low leptin,

• production decreases, which signals the brain to increase food intake

• acts on the liver and skeletal muscles, where it stimulates fatty acid oxidation in the mitochondria, which decreases fat storage

When fat cells are full,

high levels of leptin signal the brain to limit the intake of food

What do proteins provide?

energy when carbohydrates and lipids resources are not available

In what processes are the carbon atoms from amino acids used?

• in the citric acid cycle

• for the synthesis of fatty acids, ketone bodies, and glucose

What are most of the amino groups converted into?

urea

Transamination

• amino acids are degraded onto the liver

• an amino group is transferred from an amino acid to an ɑ- keto acid, usually ɑ- ketoglutarate

• a new amino acid and ɑ- keto acid are formed

• when alanine combines with ɑ- ketoglutarate, pyruvate and glutamate are produced

Oxidative deamination

• removes the ammonium group ( —NH₃⁺ ) from glutamate as an ammonium ion, NH₄⁺ , and provides hydrogens for the NAD⁺ coenzyme

• regenerates ɑ- ketoglutarate, which can enter transamination with an amino acid

The urea cycle

• removes toxic ammonium ions from amino acid degradation

• converts ammonium ions to urea in the liver

What does the urea cycle produce?

produces 25–30 grams of urea daily for excretion in the urine

Carbon skeletons of amino acids

• form intermediates of the citric acid cycle

• produce energy

• enter the citric acid cycle at different places depending on the amino acid