Chapter 4Chapter 4

(1)

Dee Unglaub Silverthorn, Ph.D.

H ^UMAN P ^HYSIOLOGY H ^UMAN P ^HYSIOLOGY

PowerPoint^® Lecture Slide Presentation by

Dr. Howard D. Booth, Professor of Biology, Eastern Michigan University

AN INTEGRATED APPROACH

T H I R D E D I T I O N

Chapter 4 Chapter 4

Cellular Metabolism

(2)

About this Chapter About this Chapter

• Energy for synthesis and movement

• Energy transformation

• Enzymes and how they speed reactions

• Metabolic pathways

• ATP its formation and uses in metabolism

• Synthesis of biologically important

molecules

(3)

• Energy does work

• Kinetic energy

• Potential energy

• Energy conversion

Energy (E) Transfer Overview

(4)

Energy (E) Transfer Overview

(5)

(6)

Chemosynthesis versus Photosynthesis Chemosynthesis versus Photosynthesis Chemosynthesis

• 6CO

₂

+ 6H

₂

S → C

₆

H

₁₂

O

₆

+ 6S Needs heat added such as from

hydrothermal vents in the deep ocean Photosynthesis

• 2n CO

2

+ 2n H

2

O + photons → 2(CH

2O)n

+ 2n O

2

Occurs in Two Stages

Stage 1: Light energy used to form ATP and

NADPH

(7)

(8)

Energy and Chemical Reactions

(9)

Formation of ATP from Carbs, Proteins and Fat Formation of ATP from Carbs, Proteins and Fat

• Enzymes of metabolic pathways are

able to capture the energy contained in

carbohydrates, proteins and fatty acids

in small portions and store it in form of

internal high energy compounds such

as ATP, drastically reducing the amount

of energy lost as heat.

(10)

Adenosine Triphosphate (ATP) Adenosine Triphosphate (ATP)

• Source of immediately usable energy for the cell

• Adenine-containing RNA nucleotide with

three phosphate groups

(11)

Adenosine Triphosphate (ATP) Adenosine Triphosphate (ATP)

Figure 2.22

(12)

How ATP Drives Cellular Work

(13)

Protein Protein

Figure 2.16

• Macromolecules composed of combinations

of 20 types of amino acids bound together

with peptide bonds

(14)

Structural Levels of Proteins Structural Levels of Proteins

• Primary – amino acid sequence

• Secondary – alpha helices or beta pleated

sheets

(15)

Structural Levels of Proteins Structural Levels of Proteins

Figure 2.17a-c

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(17)

Structural Levels of Proteins Structural Levels of Proteins

• Tertiary – superimposed folding of secondary structures

• Quaternary – polypeptide chains linked

together in a specific manner

(18)

(19)

Structural Levels of Proteins Structural Levels of Proteins

Figure 2.17d, e

(20)

Fibrous and Globular Proteins Fibrous and Globular Proteins

• Fibrous proteins

• Extended and strandlike proteins

• Examples: keratin, elastin, collagen, and certain contractile fibers

• Globular proteins

• Compact, spherical proteins with tertiary and quaternary structures

• Examples: antibodies, hormones, and

enzymes

(21)

Protein Synthesis Protein Synthesis

Figure 4-34: Summary of transcription and translation

(22)

Post – Translational protein modificaiton

(23)

• Folding, cleavage, additions: glyco- lipo- proteins

Post – Translational protein modificaiton

(24)

Characteristics of Enzymes Characteristics of Enzymes

• Most are globular proteins that act as biological catalysts

• Holoenzymes consist of an apoenzyme (protein) and a cofactor (usually an ion)

• Enzymes are chemically specific

• Frequently named for the type of reaction they catalyze

• Enzyme names usually end in -ase

• Lower activation energy

(25)

Characteristics of Enzymes Characteristics of Enzymes

Figure 2.19

(26)

Enzymes speed biochemical reactions

(27)

Mechanism of Enzyme Action Mechanism of Enzyme Action

• Enzyme binds with substrate

• Product is formed at a lower activation energy

• Product is released

(28)

• Lower activation E

• Specific

• May require Cofactors or Coenzymes

• Modulators

• Acidity

• Temperature

• Competitive inhibitors

• Allosteric

Enzymes speed biochemical reactions

(29)

Cofactors and Enzyme Activity Cofactors and Enzyme Activity

• Cofactors are inorganic substrates. Some cofactors are required to produce a

chemical reaction between the enzyme and the substrate, while others merely increase the rate of catalysis. Cofactors are

sometimes attached to the enzyme, much

like a prosthetic limb. Others are loosely

bound to the enzyme.

(30)

Coenzymes and Enzyme Activity Coenzymes and Enzyme Activity

• Unlike the inorganic cofactors, coenzymes are organic molecules. Certain enzymes need

coenzymes to bind to the substrate and cause a reaction. Since the coenzymes are changed by the chemical reaction, these are considered to be

secondary substrates of the reaction. Though

enzymes are specific to the substrate, coenzymes are not specific to the enzymes they assist. Some chemical reactions within the cells of the body do require a cofactor or a coenzyme to work properly, while others do not. The body is unable to

manufacture these products, so the way to get the vitamins necessary to produce cofactors and

coenzymes is to eat a healthy, balanced diet full of

(31)

Protein Denaturation Protein Denaturation

Figure 2.18a

• Reversible

unfolding of

proteins due

to drops in

pH and/or

increased

temperature

(32)

Protein Denaturation Protein Denaturation

• Irreversibly denatured proteins cannot

refold and are formed by extreme pH or

temperature changes

(33)

• Defined:

• Equlibrium

• Reversible Law of Mass Action Law of Mass Action

Figure 4-17: Law of mass action

(34)

• Oxidation–reduction

• Hydrolysis–dehydration

• Addition–subtraction exchange

• Ligation

Types of Enzymatic Reactions

(35)

• Pathways

• Intermediates

• Catabolic - energy

• Anabolic - synthesis Cell Metabolism Cell Metabolism

Figure 4-18b: A group of metabolic pathways resembles a road map

(36)

• Feedback inhibition

Control of Metabolic Pathways

(37)

(38)

• Glycolysis

• Pyruvate

• Anaerobic respiration

• Lactate

production

• 2 ATPs

produced

ATP Production

(39)

(40)

Glycolytic pathway defects are autosomal recessive red blood cell metabolic disorders that cause hemolytic anemia.

• The glycolytic pathway is one of the body's important metabolic pathways. It involves a sequence of enzymatic reactions that break down glucose (glycolysis) into pyruvate, creating the energy sources adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NADH). Various inherited defects in enzymes of the pathway may occur.

• The most common defect is Pyruvate kinase deficiency

• Other defects that cause hemolytic anemia include deficiencies of

• Erythrocyte hexokinase

• Glucose phosphate isomerase

• Phosphofructokinase

• In all of these pathway defects, hemolytic anemia occurs only in homozygotes. The exact mechanism of hemolysis is unknown.

• Symptoms are related to the degree of anemia and may include jaundice and

splenomegaly. Spherocytes are absent, but small numbers of irregularly shaped cells (echinocytes) may be present.

• In general, assays of ATP and diphosphoglycerate help identify any metabolic defect and localize the defective sites for further analysis.

• Treatment

• Folic acid during acute hemolysis,transfusions if needed

• Sometimes splenectomy

• There is no specific therapy for hemolytic anemias caused by glycolytic pathway defects.

Most patients require no treatment other than supplemental folic acid 1 mg po once/day

(41)

(42)

(43)

(44)

(45)

Enzyme Regulation

(46)

• Aerobic respiration

• In mitochondria

• Acetyl CoA and CO

2

• Citric Acid Cycle or Kreb’s Cycle or TCA Cycle

• Energy Produced from 1 Acetyl CoA

• 1 ATP

• 3 NADH

• 1 FADH2

Pyruvate Metabolism

(47)

Pyruvate Metabolism Pyruvate Metabolism

Figure 4-23: Pyruvate metabolism

(48)

• High energy electrons

• Energy transfer

• ATP synthesized from ADP

• H

2

O is a byproduct- In a typical individual this amounts to

approximately 400 ml/day Electron Transport

Electron Transport

(49)

Electron Transport Electron Transport

Figure 4-25: The electron transport system and ATP synthesis

(50)

(51)

• Complex

Carbohydrates

• Glycogen catabolism

• Liver storage

• Muscle storage

• Glucose produced

Biomolecules Catabolized to make ATP Biomolecules Catabolized to make ATP

Figure 4-26: Glycogen catabolism

(52)

• Deaminated

• Conversion

• Glucose

• Acetyl CoA

Protein Catabolism

(53)

Protein Catabolism Protein Catabolism

Figure 4-27: Protein catabolism and deamination

(54)

(55)

(56)

• Higher energy content

• Triglycerides to glycerol

• Glycerol

• Fatty acids

• Ketone bodies - liver Lipid Catabolism

Lipid Catabolism

(57)

Dee Unglaub Silverthorn, Ph.D.

H ^UMAN P ^HYSIOLOGY H ^UMAN P ^HYSIOLOGY

PowerPoint^® Lecture Slide Presentation by

Dr. Howard D. Booth, Professor of Biology, Eastern Michigan University

AN INTEGRATED APPROACH

T H I R D E D I T I O N

(58)

(59)

(60)

(61)

Fat mass, adipose tissue and energy stores

Data for a 70 kg lean subject.

Adipose tissue triglycerides = Adipose tissue triglycerides =

120,000 kcal 120,000 kcal

Muscle triglycerides = 3000 kcal

Liver triglycerides = 450 kcal Liver glycogen = 400 kcal

Muscle glycogen =

2500 kcal

(62)

• Glycogen synthesis

• Liver storage

• Glucose to glycogen

• Gluconeogenesi s

• Amino acids

• Glycerol

Synthetic (Anabolic) pathways

(63)

• Acetyl Co A

• Glycerol

• Fatty acids

• Triglycerides Lipogenesis

Lipogenesis

Figure 4-30: Lipid synthesis

(64)

Lipogenesis

(65)

Chapter 4Chapter 4

Dee Unglaub Silverthorn, Ph.D.

H UMAN P HYSIOLOGY H UMAN P HYSIOLOGY

AN INTEGRATED APPROACH

Chapter 4 Chapter 4

Cellular Metabolism

About this Chapter About this Chapter

• Energy for synthesis and movement

• Energy transformation

• Enzymes and how they speed reactions

• Metabolic pathways

• ATP its formation and uses in metabolism

• Synthesis of biologically important

molecules

• Energy does work

• Kinetic energy

• Potential energy

• Energy conversion

Energy (E) Transfer Overview

Energy (E) Transfer Overview

Energy (E) Transfer Overview

Energy (E) Transfer Overview

Chemosynthesis versus Photosynthesis Chemosynthesis versus Photosynthesis Chemosynthesis

• 6CO

+ 6H

S → C

H

O

+ 6S Needs heat added such as from

hydrothermal vents in the deep ocean Photosynthesis

• 2n CO

+ 2n H

O + photons → 2(CH

+ 2n O

Occurs in Two Stages

Stage 1: Light energy used to form ATP and

NADPH

Energy and Chemical Reactions

Energy and Chemical Reactions

Formation of ATP from Carbs, Proteins and Fat Formation of ATP from Carbs, Proteins and Fat

• Enzymes of metabolic pathways are

able to capture the energy contained in

carbohydrates, proteins and fatty acids

in small portions and store it in form of

internal high energy compounds such

as ATP, drastically reducing the amount

of energy lost as heat.

Adenosine Triphosphate (ATP) Adenosine Triphosphate (ATP)

• Source of immediately usable energy for the cell

• Adenine-containing RNA nucleotide with

three phosphate groups

Adenosine Triphosphate (ATP) Adenosine Triphosphate (ATP)

How ATP Drives Cellular Work

How ATP Drives Cellular Work

Protein Protein

• Macromolecules composed of combinations

of 20 types of amino acids bound together

with peptide bonds

Structural Levels of Proteins Structural Levels of Proteins

• Primary – amino acid sequence

• Secondary – alpha helices or beta pleated

sheets

Structural Levels of Proteins Structural Levels of Proteins

Structural Levels of Proteins Structural Levels of Proteins

• Tertiary – superimposed folding of secondary structures

• Quaternary – polypeptide chains linked

together in a specific manner

Structural Levels of Proteins Structural Levels of Proteins

Fibrous and Globular Proteins Fibrous and Globular Proteins

• Fibrous proteins

• Extended and strandlike proteins

• Examples: keratin, elastin, collagen, and certain contractile fibers

• Globular proteins

• Compact, spherical proteins with tertiary and quaternary structures

• Examples: antibodies, hormones, and

enzymes

Protein Synthesis Protein Synthesis

Post – Translational protein modificaiton

Post – Translational protein modificaiton

• Folding, cleavage, additions: glyco- lipo- proteins

H ^UMAN P ^HYSIOLOGY H ^UMAN P ^HYSIOLOGY