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Given the rich complexity of life on

Earth, we might expect organisms to

have an enormous diversity of molecules

The critically important large molecules

of all living things fall into just four main

classes: carbohydrates, lipids, proteins,

and nucleic acids

Carbohydrates, proteins, and nucleic acids are huge and are thus called macromolecules.

Carbohydrates, proteins and nucleic acids are chain like molecules called polymers

A polymer is a long molecule consisting of many building blocks linked by covalent bonds. The repeating units are called monomers.

The chemical mechanism by which all cells make and break down polymers are the same

Monomers are connected by a condensation reaction (dehydration reaction), because water is the molecule that is lost

This reaction can be repeated as monomers are added to the chain, making a polymer

Facilitated by enzymes: specialized macromolecules that speed up chemical reactions in cells

Polymers are disassembled to monomers by hydrolysis, a process that is essentially the reverse of the dehydration reaction

Example: digestion. Within the digestive tract, various enzymes attack the polymers, speeding up hydrolysis. The released monomers are then absorbed into the bloodstream for distribution to all body cells

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Each cell has thousands of different kinds of macromolecules; the collection varies from one type of cell to another (even in the same organism)

These molecules are constructed from only 40-50 common monomers

It is analogous to constructing hundreds of thousands of words from only 26 letters of the alphabet

I. Carbohydrates1. Simple sugars (monosaccharides,

disaccharides)

2. Polysaccharides

II. Lipids1. Fats

2. Phospholipids

3. Steroids

III. Proteins1. Polypeptides

IV. Nucleic Acids

Carbohydrates include both sugars and

polymers of sugars

The simplest carbohydrates are the

monosaccharides (simple sugars)

Disaccharides are double sugars

Macromolecules are called

polysaccharides

Monosaccharides generally have

molecular formulas that are multiples of

the unit CH2O

Most names for sugars end in –ose

Glucose (C6H12O6) is the most common

monosaccharide

The molecules have:• carbonyl group (C=O)

• multiple hydroxyl groups (-OH)

They are named according to the source

where they were first extracted, the

presence of certain chemical groups, or

the number of carbons in the skeleton

Another source of diversity for simple

sugars is in the spatial arrangement of

their parts around asymmetric carbons

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Although it is convenient to draw glucose

with a linear carbon skeleton, sugars may

form rings

In the process known as cellular

respiration, cells extract energy in a

series of reactions starting with glucose

molecules

The carbon skeletons of sugars also

serve as raw material for the synthesis of

other types of small organic molecules

A disaccharide consists of two

monosaccharides joined by a glycosidic

linkage (dehydration reaction)

Maltose is a disaccharide formed by the

linking of two molecules of glucose

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Another prevalent disaccharide is

sucrose, which is table sugar. Its two

monomers are glucose and fructose

Lactose, the sugar present in milk, is

another disaccharide, in this case, a

glucose + galactose molecule

Polymers with a few hundred to a few

thousand monosaccharides joined by

glycosidic linkages

Serve as:

• Storage material: hydrolyzed as needed to

provide sugar for cells

• Building material for structures that protect the

cell or the whole organism

Both plants and animals store sugars for

later use in the form of storage

polysaccharides:

• Plants store starch

• Animals store glycogen

Polymer of glucose monomer

Granules within cellular structures known

as plastid (like chloroplasts)

Starch represents stored energy. The

sugar can later be withdrawn by

hydrolysis

Potato tubers and grains (wheat, corn,

rice) are the major sources of starch in

the human diet

Glucose monomers in starch are joined

by 1-4 linkages (carbon 1 to carbon 4)

The angle makes the polymer helical

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Amylose is an

unbranched

molecule

Amylopectin

(more complex

starch) is

branched, with 1-

6 linkages at the

branch points

Animals store a

polysaccharide

called glycogen, a

polymer of glucose

that is extensively

branched

Glycogen is stored

mainly in liver and

muscle cells

Hydrolysis of glycogen in these cells

releases glucose when the demand for

sugar increases

In humans, glycogen stores are depleted

in about a day and have to be

replenished by food consumption

THIS IS AN ISSUE OF CONCERN IN

LOW-CARBOHYRATE DIETS

Organisms build strong materials from

structural polysaccharides

Cellulose is a major component of the

tough walls that enclose plant cells

Cellulose is the most abundant organic

compound on Earth (about 100 billion

tons per year)

Polymer of glucose, but the glycosidic

linkages differ

When glucose forms a ring, the hydroxyl

group attached to the number 1 carbon is

positioned either below or above the

plane of the ring (alpha or beta

configuration)

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In starch, all the glucose monomers are in

the alpha configuration

Glucose monomers of cellulose are all in

the beta configuration, making every

other glucose monomer upside down

with respect to its neighbors

The different glycosidic linkages give the

two molecules distinct 3D shapes:

• Starch is mostly helical

• Cellulose is straight

Cellulose is never branched and can

form H-bonds with the hydroxyls of other

cellulose molecules

In plant cell walls, parallel cellulose

molecules held together in this way are

grouped into units called microfibrils

Cellulose is the major constituent of

paper and the only component of cotton

There are specific enzymes to hydrolyze

alpha and beta linkages

Few organisms possess enzymes that can

digest cellulose: Humans DO NOT

The cellulose in our food passes through

the digestive tract and is eliminated with

the feces.

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Some prokaryotes can digest cellulose,

breaking it down into glucose monomers.

A cow harbors cellulose-digesting

organisms in its rumen

Termites also have organisms living in

their guts that allow them to eat wood

Some fungi can also digest cellulose,

helping them recycle elements in the

ecosystem

Another important structural

polysaccharide similar to cellulose, but

has a nitrogen-containing side group

Used by arthropods to build their

exoskeletons (jointed shell surrounding

the soft parts of the animal)

Chitin is also found in cell walls of fungi

Lipids are the one class of large

biological molecules that does not

include true polymers

Mix poorly (if at all) with water

(hydrophobic behavior)

Lipids consist mostly of hydrocarbon

regions and are varied in form and

function

A fat is constructed from two kinds of

smaller molecules:

• Glycerol

• fatty acids

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Glycerol is an alcohol with three carbons, each

bearing a hydroxyl group

A fatty acid has a long hydrocarbon chain, usually

16 or 18 C atoms in length. The carbon at one end

has a carboxyl group (hence the name „fatty acid‟)

These two molecules assemble by dehydration In making a fat, three fatty acid molecules each join to glycerol by an ester linkage (a bond between a –OH and a -COOH)

The resulting fat is also called a triacylglycerol (also triglyceride)

The fatty acids can be the same or 3 different

Fatty acids vary in length and in the

number and locations of double bonds:

• Saturated fats

• Unsaturated fats

They refer to the structure of the

hydrocarbon chains of the fatty acids:• No double bonds between C = saturated with H

• An unsaturated fatty acid has one or more

double bonds (may kink its hydrocarbon chain)

A fat made from saturated fatty acids is called a saturated fat

Most animal fats are saturated (tails of the fat molecules lack double bonds). Solid at room temp

The fats of plants and fishes are generally unsaturated, and usually liquid at room temperature, and referred to as oils (olive oil, cod liver oil, all have cis double bonds)

Hydrogenated vegetable oils refers to oils that have been synthetically converted to saturated fats by adding hydrogen (peanut butter, margarine

A diet rich in saturated fats may contribute to cardiovascular disease (atherosclerosis)

Recent studies have shown that the process of hydrogenating vegetable oils produce unsaturated fats with trans double bonds These trans fats may contribute more than saturated fats to atherosclerosis

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Fat has come to have such a negative connotation in our culture that you might wonder what useful purpose fats serve

The major function is energy storage:• a gram of fat stores more than twice as much energy

as a gram of a polysaccharide (starch)

Plants are relatively immobile, so they can function with bulky energy storage in the form of starch

Humans and other mammals stock their

long-term food reserves in adipose cells

Adipose tissue also cushions such vital

organs

The layer of fat beneath the skin insulates

the body (especially thick in whales,

seals, and other marine mammals)

Fig. 4-6

(a) Mammalian adipose cells (b) A fat molecule

Fat droplets (stained red)

100 µm

Phospholipids are essential for cells

because they make up cell membranes

A phospholipid is similar to a fat

molecule but has only two fatty acids

attached to glycerol rather than three

The 3rd hydroxyl group of glycerol is

joined to a phosphate group, which has a

negative electrical charge

When phospholipids are added to water,

they self-assemble into bilayers that shield

their hydrophobic portions from water

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At the surface of the cell, phospholipids

are also arranged in a bilayer

• Hydrophilic heads: outside, in contact with the

aqueous solutions inside and outside of the cell

• The hydrophobic tails: toward the interior of the

bilayer

Lipids characterized by a carbon

skeleton consisting of four fused rings

Hormones and cholesterol are steroids

Cholesterol is a common component of

animal cell membranes and is also a

precursor from which other steroids are

synthesized

Cholesterol is synthesized in the liver

Many hormones are steroids produced from cholesterol

Cholesterol is a crucial molecule in animals, but high levels in blood may contribute to atherosclerosis

Saturated fats and trans fats exert their negative effect on health by affecting cholesterol levels.

Proteins account for more than 50% of

the dry mass of most cells

They are the most structurally

sophisticated molecules know, which is

consistent with their diverse functions

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Life would not be possible without

enzymes, most of which are proteins

Enzymatic proteins regulate metabolism

by acting as catalysts, chemical agents

that selectively speed up chemical

reactions without being consumed by the

reaction

All proteins are made up of the same set

of 20 amino acids (aa)

A protein consists of one or more

polypeptides, each folded and coiled

into a specific three-dimensional

structure

AA are organic molecules possessing both carboxyl and amino groups

The general formula is:• In the center: the asymmetric carbon (alpha

carbon)

• amino group

• carboxyl group

• hydrogen atom

• variable group (R)

Amino acids can be identified with a

single letter or a three letter system.

The physical and chemical properties of

the side chain determine the unique

characteristics of a particular amino acid

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Structure of

the 20 most

common

aa‟s

depicted in

ionized form

You can link two amino acids by

positioning them so that the carboxyl

group of one (-COOH) is adjacent to the

amino group of another (-NH2)

A dehydration reaction will result in a

covalent bond called a peptide bond

At one end of the polypeptide chain is a

free amino group

At the opposite end is a free carboxyl

group (N-terminus and C-terminus)

The side chains of the aa‟s extend from

the backbone

The term polypeptide is not synonymous

with the term protein

The relationship is analogous to that

between a long strand of yarn and a sweater

A protein is not just a polypeptide chain, but

one or more polypeptides precisely twisted,

folded and coiled into a molecule of unique

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The amino acid sequence ultimately determines the 3D structure of the protein

The specific structure determines how it works because it confers it the ability to recognize and bind to some other molecule. Ex:

• antibody and a foreign substance

• enzyme we saw in fig 5.16

• endorphins we saw in Chapter 2 (bind to specific receptors on brain cells)

The function of a protein is an emergent property resulting from exquisite molecular order.

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Two types of nucleic acids enable living

organisms to reproduce their complex

components from one generation to the

next:• deoxyribonucleic acid (DNA)

• ribonucleic acid (RNA)

Nucleic acids are macromolecules that

exist as polymers called polynucleotides

The monomers are called nucleotides:

-Nitrogenous base

-A Sugar (pentose, 5 C)

(NB + Sugar = Nucleoside)

-A phosphate group

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Base because the N atoms take up H+ form solution

There are two families of nitrogenous bases:• Pyrimidines• Purines

A pyrimidine has a six-membered ring of carbon and nitrogen atoms: Cytosine, Thymine and Uracil

A purine is larger, with a six-membered ring fused to a five-membered ring: Adenine and Guanine are purines

The sugar that connects to the NB is deoxyribose in DNA and ribose in RNA

A NB + a Pentose make up a nucleoside

Deoxyribose lacks an oxygen atom on the second carbon in the ring. The sugar atoms have a prime („) after the number to distinguish them from the NB numbers.

Ex: the 2‟ carbon is the one that sticks up from the ring

The phosphate group is attached to the 5‟

carbon of the sugar making a molecule

called nucleoside monophosphate, better

known as a nucleotide

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Adjacent nucleotides are joined by a

phosphodiester linkage, which consists

of a phosphate group that links the

sugars of two nucleotides

The backbone will end up with a

repeating pattern of sugar-phosphate

units.

The two free ends of the polymer are

distinctly different from each other:

• one end has a phosphate attached to a 5‟ carbon

(5‟ end )

• the other end has a hydroxyl group on a 3‟ (3‟

end) carbon

All along this sugar-phosphate backbone

are appendages consisting of the

nitrogenous bases.

The sequence of bases along DNA (or

RNA) is unique for each gene and

provides very specific information to the

cell

A gene‟s meaning to the cell is encoded

in its specific sequence of the four DNA

bases

The linear order of bases in a gene

specifies the amino acid sequence.

Unique among molecules, DNA provides directions for its own replication

DNA also directs RNA synthesis and, through RNA, controls protein synthesis

DNA is the genetic material that organisms inherit from their parents

Long molecules of DNA are packed into structures called chromosomes, each carrying several hundred or more genes.

When a cell reproduces itself by dividing, its DNA molecules are copied and passed along from one generation of cells to the next

It is composed of:

-Nitrogenous bases: C, T, A, G

-Deoxyribose

-Phosphate group

DNA molecules have two polynucleotide

chains that spiral around an imaginary

axis, forming a double helix

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Watson and Crick (Cambridge, 1953)

proposed the 3D model for the first time

Antiparallelarrangement: the two sugar-phosphate backbones run in opposite 5‟ > 3‟ directions

The sugar-phosphate backbones are on the outside of the helix

NB are paired in the interior of the helix.

The two strands are held together by:• H bonds between the paired bases

• Van der Waals interactions between the stacked bases

A pairs with T, G pairs with C

The two strands of the double helix are complementary

This unique feature is what makes possible the precise copying of genes that is responsible for inheritance.

In preparation for ell division, each of the two strands of a DNA molecule serves a a template to order nucleotides on the new complementary strand

The result is two identical copies of the original double-stranded DNA molecule, which are then distributed to the two daughter cells

It is composed of:

-Nitrogenous bases: C, U, A, G

-Ribose

-Phosphate group

RNA molecules consist of a single

polynucleotide chain

Encoded in the structure of DNA is the information that programs all the cell‟s activities

Proteins are required to implement genetic programs, kind of a tool for biological function

Each gene along a DNA molecule directs synthesis of a type of RNA called messenger RNA(mRNA)

mRNA interacts with ribosomes, and the sequence information in the mRNA directs the production of a polypeptide, which folds to create a protein

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Proteinacous Infectious Particles

Cause neurological degenerative

diseases known as Spongiform

Encephalopathies

Are resistant to destruction by burning,

cooking, formaldehyde, alcohol, UV light,

proteases & nucleases

Can in many cases be infectious to

humans and other mammals

S.B Prusiner, UCSF, Nobel

Prize 1998

The scrapie Prion is not a

virus but a protein: PrPSC

Wild type PrPC PrPSC

3° structure as template

Onset of disease due to

accumulation of PrPSC

a copper-binding protein

that “donates” copper to

super oxide dismutase?Brown, 2001. Brain Res. Bull

15:165-73

conserved in mammals

minor amino acid

differences in proteins

from different species

not essential

normal

proteins

abnormal

protein

Protein conversion

not replication

PrPc PrPSc

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PrP PrPSc

Model of scrapie prion based on PrP 27-30

Source: Prion Biology and Diseases, S. Prusiner Ed. (Cold Spring Harbor, 2004)

protofibril

protofibrils

cell death

Discovered in 1921 by Dr. Hans Gerhard Creutzfeldt and Dr. Alfons Jakob, University of Hamburg Germany

Occurs worldwide: 1 in 1 million/year, usually ages 55-75

Physical attributes of the affected brain:

• Enlarged astrocytes- Star shaped cells attached to blood vessels in brain

• Holes where neurons used to be

• Amyloid Plaques-protein waxy buildup in cells.

Microscope slide of brain

affected by CJD

(first 7 same as BSE)

restlessness

aggressiveness (biting and hitting)

loss of motor function

loss of appetite

convulsions

blindness

self mutilation

inability to swallow

90% of deaths usually occur within one year of diagnosis, difficult to confirm diagnosis until post mortem.

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Known to have

existed for at least

200 years without

being transmitted to

humans, while being

endemic in sheep

populations all over

the world.

Affected only a tribal culture of

Papua, New Guinea that

practiced ritualistic cannibalism.

5-10 % of the population died

each year from kuru.

When a loved one died the body

was cooked, the men ate muscle

portions, while the women and

children were left with the lesser

organs and brain (where prions

tend to cluster).

The rare male cases of kuru

occurred later in life after a

dormancy period (due to

infectious agents ingested as

children).

Initially believed to be a virus

causing encephalitis with

similar symptoms as

Parkinson's, Alzheimer's, and

MS.

After some victims were given

autopsies, the connection of

brain damage to recently

discovered CJD was realized.

When cannibalism was

ceased in the 1960s kuru

disappeared

Humans can acquire the prion by exposure to meat that has become contaminated with the brain or spinal matter of an infected animal.

Surgical equipment can be unknowingly infected by use on a patient with vCJD, and because sterilization techniques do not destroy prions, which are transmitted to the other patients in subsequent procedures.

Debate

• Whether prions are the agent which causes disease

or merely a symptom caused by a different agent is

still debated by a minority of researchers

Protein hypothesis

• Prior to the discovery of prions, it was thought that

all pathogens used nucleic acids to direct their

replication. The "protein hypothesis" states that a

protein structure can replicate without the use of

nucleic acid. This was initially controversial as it

seemed to contradict the "central dogma of

molecular biology”.

Viral hypothesis

• The protein-only hypothesis has been criticized by

those who feel that the simplest explanation of the

evidence to date is viral.