The Structure and Function of

Macromolecules

林谷峻Gu-Jiun Lin

國防醫學院 生物及解剖學研究所

National Defense Medical Center

Graduate Institute of Biology and Anatomy

Office: 5358

Phone: 18709

e-mail: lingujiun@mail.ndmctsgh.edu.tw

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Overview：Carbon—The Backbone of

Biological Molecules

What properties make carbon the basis of the life

Although cells are 70–95% water, the rest consists mostly of carbon-

based compounds

Carbon is unparalleled in its ability to form large, complex, and diverse

molecules

Proteins, DNA, carbohydrates, and other molecules that distinguish living

matter are all composed of carbon compounds

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Concept 4.1: Organic chemistry is the study

of carbon compounds (有機化學)1. Organic compounds有機化合物--range from simple molecules to colossal

ones

2. Most organic compounds contain hydrogen atoms in addition to carbon atoms

3. Vitalism (生機說) was the belief in a life force outside the jurisdiction of physical and chemical laws

4. It was thought that organic compounds could only be produced in living organisms

5. Vitalism was disproved when chemists were able to synthesize organic compounds

Carbon can bond to four other atoms or

groups of atoms, making a large variety of

molecules possible.

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Organic Molecules and the Origin of Life on Earth

EXPERIMENT

In 1953, Stanley Miller simulated what were

thought to be environmental conditions on the

lifeless, primordial Earth. As shown in this

recreation, Miller used electrical discharges

(simulated lightning) to trigger reactions in a

primitive “atmosphere” of H2O, H2, NH3

(ammonia), and CH4 (methane)—some of the

gases released by volcanoes.

• Stanley Miller’s classic experiment demonstrated the abiotic synthesis of

organic compounds

• Experiments support the idea that abiotic synthesis of organic compounds,

perhaps near volcanoes, could have been a stage in the origin of life

• Pioneers of organic chemistry helped shift the mainstream of biological

thought from vitalism to mechanism (機械論)

• Mechanism is the view that physical and chemical laws govern all natural

phenomena

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A variety of organic compounds that

play key roles in living cells were

synthesized in Miller’s apparatus.

RESULTS

CONCLUSION

Organic compounds may have been

synthesized abiotically on the early Earth,

setting the stage for the origin of life.

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Concept 4.2: Carbon atoms can form diverse

molecules by bonding to four other atoms

The formation of bonds with carbon : tetravalence 四價a. Organic compounds

The shapes of three simple organic molecular.

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c. Carbon skeletons碳骨架

b. Covalent bonds共價鍵

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B.Molecular diversity arising from carbon skeleton

variation

1.Hydrocarbons 碳氫化合物

The role of hydrocarbons in fats

1. Hydrocarbons are organic molecules

consisting of only carbon and

hydrogen

2. Many organic molecules, such as

fats, have hydrocarbon components

3. Hydrocarbons can undergo reactions

that release a large amount of energy

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2. Isomers 同分異構物

Three types isomers, compounds with

the same molecular formula but different

structures

• Isomers are compounds with the

same molecular formula but

different structures and properties

– Structural isomers (結構異構物) have different covalent

arrangements of their atoms

– Cis-trans isomers (順式及反式異構物或幾何異構物 )

have the same covalent bonds

but differ in spatial

arrangements

– Enantiomers (鏡像異構物)

are isomers that are mirror

images of each other : D-

(dextro右) form; L-(levo左)

form.

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The pharmacological importance of enantiomers

• Enantiomers are important in the pharmaceutical industry

• Two enantiomers of a drug may have different effects

• Usually only one isomer is biologically active

• Differing effects of enantiomers demonstrate that organisms are sensitive

to even subtle variations in molecules

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Concept 4.3: A few chemical groups are key to

molecular function

A comparison of chemical groups of female (estradiol) and male (testosterone)

A. The chemical groups most important in the processes of life Estradiol and testosterone are both steroids with a common carbon skeleton,

in the form of four fused rings

These sex hormones differ only in the chemical groups attached to the rings

of the carbon skeleton

Distinctive properties of organic molecules depend on the carbon skeleton and

on the chemical groups attached to it

A number of characteristic groups can replace the hydrogens attached to

skeletons of organic molecules

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Functional groups are the parts of molecules involved in chemical reactions官能基

*Polar, hydrophlic極性的，親水性的

1. Hydroxyl group羥基, -OH；alcohol

2. Carbonyl group羰基, >C=O；ketones, aldehydes

3. Carboxyl group羧基, -COOH；carboxylic acids

4. Amino group胺基, -NH2；amines

5. Sulfhydryl硫氫基, -SH；thiol

6. Phosphate group磷酸基, -OPO32-；organic phosphate

7. Methyl group 甲基-CH3, methylated compounds

FUNCTIONAL

GROUP

(may be written HO )

HYDROXYL CARBONYL CARBOXYL

OH C

O O

C

OH

AMINO SULFHYDRYL PHOSPHATE

(may be written HS )N

H

H

SH

O P

O

OH

OH

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羥基

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羰基

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羧基

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胺基

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硫氫基

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磷酸基

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甲基

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B. ATP: An important source of energy for cellular processes

• One phosphate molecule, adenosine triphosphate (ATP), is the primary

energy-transferring molecule in the cell

• ATP consists of an organic molecule called adenosine attached to a string

of three phosphate groups

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You should now be able to:

• Explain how carbon’s electron configuration explains its

ability to form large, complex, diverse organic molecules

• Describe how carbon skeletons may vary and explain how

this variation contributes to the diversity and complexity of

organic molecules

• Distinguish among the three types of isomers: structural,

geometric, and enantiomer

• Name the major functional groups found in organic

molecules; describe the basic structure of each functional

group and outline the chemical properties of the organic

molecules in which they occur

• Explain how ATP functions as the primary energy transfer

molecule in living cells

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Ch5 Biological Macromolecules

and LipidsOverview: The Molecules of Life

All living things are made up of four classes of large biological molecules: carbohydrates, lipids, proteins, and nucleic acids

Macromolecules are large molecules and are complex

Large biological molecules have unique properties that arise from the orderly arrangement of their atoms

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Concept 5.1: Macromolecules are polymers, built from monomers大分子，聚合物，單體

Three of the four classes of life’s organic molecules are polymers 1.

carbohydrates, 2.proteins, and 3. nucleic acids

A. The synthesis and breakdown of polymers Condensation reaction (dehydration reaction) 縮合反應，脫水反應 Hydrolysis 水解

B. The diversity of polymers1. Each cell has thousands of different kinds of macromolecules.2. This diversity comes from various combinations of the 40–50 common

monomers and some others that occur rarely

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Concept 5.2: Carbohydrates serve as fuel and building material 醣類A. Sugars1. Monosaccharides單醣類--(CH2O)n；are the simplest sugars, be used

for fuel, be converted into other organic molecules and are combined into polymersa. Carbonyl group (C=O) and hydroxyl group (-OH) 羰基，羥基b. Aldose and ketose醛醣及酮醣

- glucose and galactose葡萄糖及半乳糖

- fructose 果糖

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c. Carbon skeleton 碳骨架- triose, pentose, and hexose 三碳醣，五碳醣及六碳醣

d. Spatial arrangement 空間排列

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e. Linear and ring forms 線型與環型

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2. Disaccharides 雙醣類a. Glycosidic linkage 糖苷鍵b. Maltose, sucrose and lactose 麥芽糖，蔗糖，乳糖

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B. Polysaccharides 多醣類1. Storage polysaccharides 儲存性多醣a. Starch 澱粉

• α glucose• amylose and amylopectin

直鏈澱粉，分枝澱粉b. Glycogen 肝糖

31Starch and cellulose structure

•Polymers with glucose are helical; Polymers with glucose are straight

2. Structural polysaccharides 結構性多醣a. Cellulose 纖維素

- β glucose

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Cellulose digesting prokaryotes are found

in grazing such as this cow

1014 kg/year

Enzymes that digest starch by hydrolyzing linkages can’t hydrolyze linkages in

cellulose

The cellulose in human food passes through the digestive tract as “insoluble fiber”

Some microbes use enzymes to digest cellulose

Many herbivores, from cows to termites, have symbiotic relationships with these

microbes

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b. Chitin 幾丁質

Chitin, another structural

polysaccharide, is found in

the exoskeleton of

arthropods

Chitin also provides

structural support for the cell

walls of many fungi

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Concept 5.3: Lipids are a diverse group of hydrophobic molecules 脂質，疏水性的A. Fats 脂肪：Lipids are the one class of large biological molecules that

do not consist of polymers; share the common trait of being hydrophobic

1. Triacylglycerol 三醯甘油(or triglyceride 甘油三酸脂)a. Glycerol and fatty acids 甘油及脂肪酸

b. Ester linkage 酯鍵

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2. Saturated and unsaturated fats 飽和與不飽和脂肪- Hydrogenated vegetable oil 氫化植物油

trans fats反式脂肪

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Plaques and atherosclerosis 斑塊及動脈粥狀硬化

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B. Phospholipids 磷脂:Cell membranesPhospholipids have only two fatty acids, have a phosphate group instead of a third fatty acid

1. Hydrophobic tail and hydrophilic head 親水性的

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2. Phospholipid bilayer 磷脂雙層

Bilayer structure formed by self-assembly of phospholipids

in an aqueous environment

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C. Steroids 類固醇: Steroids are lipids characterized by a

carbon skeleton consisting of four fused rings

1. Cholesterol (膽固醇), a type of steroid, is a component in animal cell membranes and a precursor from which other steroids are synthesized

2. Sex hormones

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Concept 5.4: Proteins include a diversity of structures, resulting in a wide range of functions

Proteins account for more than 50% of the dry mass of most cells.

Protein functions include structural support, storage, transport, cellular communications, movement, and defense against foreign substances

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•Enzymes酶 are a type of protein that acts as a catalyst催化劑 to speed up chemical reactions

•Enzymes can perform their functions repeatedly, functioning as workhorses that carry out the processes of life

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Casein : 酪蛋白Ovalbumine :卵白蛋白

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B. Polypeptide 多胜肽1. Amino acid monomers 胺基酸

a. Amino group and carboxyl group 胺基及羧基

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b. The 20 amino acids of proteins：differ in their properties due to differing side chains, called R groups

- nonpolar, hydrophobic 非極性

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- polar, hydrophilic 極性- electrically charged, hydrophilic 帶電荷的

*acidic or basic 酸性或鹼性

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2. Polypeptides (Amino acid polymers)a. Peptide bond 胜肽鍵b. Amino end (N-terminus)

and carboxyl end (C-

terminus)N端及C端

Frederick Sanger

1940~1950 insulin

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C. Protein structure and function

Fig Structure of lysozyme

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The exact match of shape between an antibody and the particular

foreign antigen

•The sequence of amino acids determines a protein’s three-dimensional

structure, and the structure determines its function

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1. Four levels of protein structure

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a. Primary structure初級結構• unique sequence of amino acids

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b. Secondary structure次級結構• hydrogen bonds between the

polypeptide backbone• helix or pleated sheet 螺旋或褶板

x

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c. Tertiary structure三級結構• interactions between the side chains of amino acids

*weak interactions: hydrophobic interactions, hydrogen bond,ionic bond

*covalent linkage: disulfide bridges雙硫鍵

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d. Quaternary structure四級結構• polypeptide subunits次單位

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2. Sickle-cell disease: a simple change in primary structure鎌狀細胞疾病

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3. What determines protein structure?a. Factors determining conformation: physical and chemical

conditions of the protein’s environment.

b. Denaturation and renaturation 變性及復性

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4. Protein folding in the cell

a. Chaperonins (chaperone proteins) 伴護蛋白

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b. X-ray crystallography is used to determine a protein’s

three-dimensional (3D) structure

NMR:

Nuclear magnetic resonance

Roger Kornberg

1950

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Concept 5.5: Nucleic acids store, transmit, and help express hereditary information

(Central dogma)

A. The roles of nucleic acids• There are two types of nucleic acids

– Deoxyribonucleic acid (DNA)

去氧核糖核酸

– Ribonucleic acid (RNA)

核糖核酸

• DNA provides directions for its own

replication

• DNA directs synthesis of messenger RNA

(mRNA) and, through mRNA, controls

protein synthesis

• The mRNA molecule interacts with the

cell’s protein-synthesizing machinery to

direct production of a polypeptide

• The flow of genetic information can be

summarized as DNA → RNA → protein

• This process is called gene expression (基因表達)

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B. The Components of Nucleic Acids

Nucleotide monomers 核苷酸：are made up of nucleosides核苷and phosphate groupsa. Nitrogenous bases 含氮鹼基• pyrimidines 嘧啶類

*cytosine (C), thymine (T),uracil(U)胞嘧啶，胸腺嘧啶，脲嘧啶

• purines 嘌呤類*adenine (A), guanine (G)腺嘌呤，鳥糞嘌呤

b. Pentose (five-carbon sugar)五碳醣

• ribose 核糖• deoxyribose 去氧核糖c. Phosphate group 磷酸根

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C. Nucleotide polymers： are made up of nucleotides

linked by the–OH group on the 3´ carbon of one nucleotide and

the phosphate on the 5´ carbon on the next.

*Phosphodiester linkage 磷酸二酯鍵

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RNA molecules usually exist as single polynucleotides chains

DNA molecules have two polynucleotides spiraling around an imaginary axis, forming a double helix

In the DNA double helix, the two backbones run in opposite 5→ 3directions from each other, an arrangement referred to as antiparallel逆向平行

One DNA molecule includes many genes

The nitrogenous bases in DNA pair up and form hydrogen bonds: adenine (A) always with thymine (T), and guanine (G) always with cytosine (C)

Called complementary base pairing

Complementary pairing互補can also occur between two RNA molecules or between parts of the same molecule

In RNA, thymine is replaced by uracil (U)

so A and U pair

D. The Structures of DNA and RNA Molecules

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The Structures of DNA and RNA Molecules

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Concept 5.6: Genomics and proteomics have transformed biological inquiry and applications

Once the structure of DNA and its relationship to amino acid sequence was

understood, biologists sought to “decode” genes by learning their base

sequences

The first chemical techniques for DNA sequencing were developed in the

1970s and refined over the next 20 years

It is enlightening to sequence the full complement of DNA in an organism’s

genome

The rapid development of faster and less expensive methods of sequencing

was a side effect of the Human Genome Project

Many genomes have been sequenced, generating reams of data

Bioinformatics uses computer software and other computational tools to deal

with the data resulting from sequencing many genomes

Analyzing large sets of genes or even comparing whole genomes of different

species is called genomics (基因體學)

A similar analysis of large sets of proteins including their sequences is called

proteomics (蛋白質體學)

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MAKE CONNECTIONSContributions of Genomics and Proteomics to Biology

Paleontology Evolution

HippopotamusShort-finned pilot whale

Medical Science Conservation BiologySpeciesInteractions

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DNA and proteins as tape measures of evolution 測量尺1. Sequences of genes and their protein products document the hereditary background

of an organism

2. Linear sequences of DNA molecules are passed from parents to offspring

3. We can extend the concept of “molecular genealogy” to relationships between

species

4. Molecular biology has added a new measure to the toolkit of evolutionary biology

Analyzing polypeptide sequence data

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You should now be able to:

•List and describe the four major classes of molecules

•Describe the formation of a glycosidic linkage and distinguish

between monosaccharides, disaccharides, and polysaccharides

•Distinguish between saturated and unsaturated fats and between

cis and trans fat molecules

•Describe the four levels of protein structure

•Distinguish between the following pairs: pyrimidine and purine,

nucleotide and nucleoside, ribose and deoxyribose, the 5 end and

3 end of a nucleotide

The Ends