1

MCB 3020, Spring 20051-10-2004

Chapter 3:The Building Blocks of Life I

2Chapter 3

I. The chemistry of life II. Macromolecules of the cell

A. polysaccharidesB. lipidsC. nucleic acidsD. proteins

3

CH2-CH2 CH2- O-P=OO O ORC=O C=O CH2 CH2 CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH2 CH2

CH3 CH3

O-

membrane lipids

All cells are made of organic molecules.

The Chemistry of Life

4I. The Chemistry of Life: a review

A. the 6 major bioelementsB. charge distribution in moleculesC. attractive forcesD. important functional groups

5A. The 6 Major Bioelements

C Carbon H Hydrogen O Oxygen N Nitrogen P Phosphorus S Sulfur

6

1. electronegativity2. hydrophilic (polar) 3. hydrophobic (nonpolar)4. amphipathic

B. Charge distribution in molecules

71. Electronegativity

A measure of the degree of attractionof valence electrons

Among the major bioelementsoxygen and nitrogen have the highest electronegativity

TB

82. Polar (hydrophilic)

+ -

asymmetric charge distribution in a molecule

TBH - O - CH2 CH3

9Polar molecules

H - O - H

Polar molecules result from the bonding ofatoms with very different electronegativities

TB

H - C - O-

O

103. Nonpolar (hydrophobic)

little charge asymmetry

TB

11Nonpolar molecules

hydrocarbon chain

aromatic rings

Nonpolar molecules result from the bonding ofatoms with similar electronegativities. TB

124. Amphipathic

partly polar, partly nonpolar

-negativelycharged

head

nonpolarhydrocarbon

tail

phospholipid molecule

TB

13

1. ionic bonds 2. covalent bonds3. hydrogen bonds4. van der Waals forces5. hydrophobic interactions6. comparison of bond strengths

C. Attractive forces

141. Ionic bonds

Na+ Cl-• • • •NaCl attraction between charged particles

2. Covalent bondselectron sharing between atoms

C H

HHH

• •

• •• •• • H– C – H

H

H

153. Hydrogen bonds (H-bonds)noncovalent bonds formed between the following:

1. A highly electronegative atom (usually O or N)

2. A hydrogen atom bonded toa highly electronegative atom(usually O or N) TB

16Hydrogen bonding of water molecules

H-bonding of hydroxyl groupsHOR

H

O R

H

O H

H

O H

H

O HH

O H

17

Keto groups

OR H O RH-bonds will form with various combinationsof hydroxyl, amino and keto groups thatmeet the H-bonding criteria. TB

H-bonding of amino groups

HN

R

N

R

R

R

R —

18Hydrogen bonding between amino

acids in a protein | H-C-R1 | C=O | N-H | H-C-R2 | C=O | N-H | H-C-R3 |

| R4-C-H | H –N | O=C | R5-C-H | H –N | O=C | Rc- C-H |

19Hydrogen bonding between bases in DNA

Three H-bonds between G and C

N

NNH

NN-H

H

H

Oguanine cytosine

NN

H-N-H

O H

204. van der Waals forces

+ -- +

nucleus

electronsinduced dipoles (polar)

van der Waals attractions result from attractions between induced dipoles

Attraction between molecules that are very close together

TB

215. Hydrophobic forces (interactions)Attraction between hydrophobic molecules or hydrophobic portions of molecules

TB

• driven by an increase in entropy (disorder) due to water exclusion

22Water is the biological solvent of life as we know it.• cells are 70 to 90% water • water is polar• many polar biological molecules dissolve in water• nonpolar (hydrophobic) molecules tend to aggregate together in water

236. Comparison of bond strength

1. Covalent bonds2. ionic bonds3. hydrogen bonds4. van der waals forces5. hydrophobic forces

-50 to -100-80 or -1-3 to -6-0.5 to -1-0.5 to -3

type of bond strength (kcal/mol)

24D. Important functional groups

carboxylicacid

organic acids,amino and fatty acids

Biological importance

aldehyde reducing sugars,like glucose

alcohol lipids andcarbohydrates

25Important functional groups (contd.)

ketopyruvate,citric acid cyleintermediates

lipids of Bacteriaand Eukarya

DNA, RNA,ATP

phosphoester

ester

26Important functional groups (contd.)

ether lipids(archaea)

-NH2amino amino acids,

nucleotides

27What functional groups are present

in the amino acid serine?

OH C O

H2N – C – H CH2OH

O-

C O +H3N – C – H

CH2OHserine at pH 7

28II. Macromolecules of the cell

A. polysaccharidesB. lipidsC. nucleic acidsD. proteins

29

covalent bond

polymer (eg. protein)

macromolecules are polymers of covalently linked monomers

Monomers and polymers

monomer(eg. amino acid)

30 Macromolecules are large molecules made of repeating units (monomers).

DNAa nucleic acid: a chain

(polymer) of nucleotides

a proteina polymer of amino acids

ss s

s

31Macromolecules make up 96% of the dry weight of cells.

nucleic acids

proteinspolysaccharides

lipids

32The 4 major cellular macromolecules*:chains (polymers) of repeating units

*Important recurring theme

polysaccharide sugars cell wall glycosidic

lipid fatty acids or membranes ester or ether isoprenoids

nucleic acid nucleotides DNA, RNA phosphodiester

protein amino acids enzymes peptide

polymer monomer example covalent bond(see notes for other examples)

33B. Polysaccharidespolymers of sugars linked by glycosidic bonds

1. common sugar monomers2. glycosidic bonds3. cellular polysaccharides

34

O

OHHO

OH

OH

CH2OH

a. glucose (ring form)

b. fructose (ring form) OH

O CH2OH

HO

HO

HOH2C

TB

1. common sugar monomers

35

OH

O

HOHO

HOH2C

OH

O

HO

HOH2C

c. ribose

d. deoxyribose

TB

36

O OH

HO

NH2

OH

CH2OH

e. glucosamine

f. muramic acidO OH

HO

NH2-OOCCHCH3

CH2OH

TB

372. Glycosidic bonds: a. -1,4-glycosidic bond

O

O

HO

OH

OH

CH2OHO OH

OH

OH

CH2OH

H H

38

O

O

HO

OH

OH

CH2OH

O OH

OH

OH

CH2OH

HH

b. -1,4-glycosidic bond

39

a. starch

glucose storage molecule of plants

-1,4 glycosidic bonds

mostly -1,4 glycosidic bondslarge polymer of glucose

TB

3. cellular polysaccharides

40b. glycogen

glucose storage molecule of animals and some microorganisms

-1,6-1,6

large branched polymer of glucosemostly -1,4 glycosidic bonds

TB

-1,6 glycosidic bonds produce branching

41c. cellulose

major structural polysaccharide of plants

mostly -1,4 glycosidic bondsonly microbes can break the -1,4 bond

large glucose polymer

TB

42d. peptidoglycanlarge polymer of N-acetyl glucosamine and N-acetyl muramic acidthe main structural component of most Bacterial cell walls-1,4-glycosidic bonds

*Penicillin inhibits Bacterial cell wall synthesis by inhibiting the formation of peptidoglycan. TB

431. Memorize the 6 major bioelements.2. Understand the terms electronegativity, hydrophilic, hydrophobic, polar, nonpolar, amphipathic. Know how these properties are important in chemical bonds and interactions.3. Very important recurring theme: Understand the attractive forces (ionic, covalent, hydrogen bonds, van der Waals forces, and hydrophobic interactions), the examples presented in class, where they might occur. Which are strong bonds? Which are weaker? 4. Understand the role of water as the solvent of life.5. Know the functional groups. Be able to recognize their structures. Know their biological importance and where they occur in cellular molecules. 6. Recurring theme: Know the four important cellular macromolecules (polymers), the monomers that comprise them, the bonds that connect the monomers, and the specific example presented in class. These macromolecules are the building blocks of cells.7. In what parts of cells are the four macromolecules found?

Study objectives

44Study objectives 8. Describe the structure and functions of the four cellular macromolecules, the monomers, connecting bonds. Memorize the specific examples of monomers, polymers, and bonds presented in class. 9. Be able to recognize the structures of glucose, ribose, and deoxyribose.10. Know the difference between -1,4 glycosidic bonds and -1,4-glycosidic bonds and where they can be found. Know the features of the cellular polysaccharides presented. How does penicillin inhibit microbial growth? 8.

45

MCB 3020, Spring 20041-14-2004

Chapter 2The Building Blocks of Life II:

46Chapter 2 (contd.)

II. Macromolecules of the cellA. polysaccharidesB. lipidsC. nucleic acidsD. proteins

47B. Lipids1. fatty acids (glycerol) 2. membrane lipids a. bacterial and eukaryal b. archaeal

48B. Lipids glycerol bonded to fatty acids (or isoprenoid units) and other groups by ester or ether linkages

CH2OH

CHOH

CH2OH

glycerol

OHO - C

49

palmitic (C16)COO-

COO-stearic (C18)

oleic (C18)COO-

a monounsaturated fatty acid

a. common fatty acids

TB

1. Fatty acids

50

saturated: no double bondsb. saturated and unsaturated fatty acids

COO-

monounsaturated: 1 double bond

polyunsaturated: > 1 double bondCOO-

COO-

51Unsaturated fatty acids can make the membrane more fluid.

522. Membrane lipids:

Membrane lipids are amphipathic.

hydrophobic tailpolar head

glycerol phosphate bonded to fatty acids and other groups by ester or ether bonds

53In aqueous solution lipids associatespontaneously to form bilayers that are the basis of biological membranes

The polar heads are in contact with water the nonpolar tails group with one another.

54a. bacterial and eukaryal membrane lipids

phosphatidic acidphosphatidyl ethanolaminephosphatidyl serine

fatty acids connected to glycerolphosphate through ester bonds

TB

55

fatty acid

-o-o

o-oP

o-o

-o-o

phosphatidic acid

ester bond

TB

56

o-oP

o-o

fatty acid

-o-o

-o-o

phosphatidyl ethanolamine

CH2CH2NH3+

serine

o-CH2CH2CHCOO-

NH3+

ethanolamine

TB

57b. archaeal lipidsisoprenoid units connected to glycerolphosphate through ether bonds

-O-

-O-

OH

ether bond -C-O-C-

polar nonpolar TB

58C. Nucleic acids (DNA, RNA)polymer of nucleotides covalentlylinked by phosphodiester bonds

RNADNA

591. Nucleotides = Base + sugar + phosphate(s)

(up to 3)

thymine (T) (DNA only)

cytosine (C)uracil (U) (RNA only)

OCH2

pyrimidines

adenine (A)guanine (G)

purines: O-

— P=O O-

ribose (RNA)deoxyribose

(DNA)

HOCH2

a.

60

O O - P – O -

O -O -P - O-

O O - P – O -

Detailed picture of a nucleotide (ATP)5' phosphate end

O-CH2

OH OH3' hydroxyl

ON

NH2

N

N

N

adenosine triphosphate

(ATP)

5'

61

5'

3'

b. phosphodiester bonds5'

O H

O baseOCH2 P P P

3'

5' phosphate

O-CH2

OH H

O base

3'

O = P - O-

sugars of the nucleotides are covalently linked by phosphodiester bonds

3' hydroxyl

62c. Nitrogen bases

purinesadenineguanine

pyrimidinescytosinethymineuracil

63

N

N NH

N NH2H

O

guanine

N

N N

N

NH2

H

adenine

Purines

TB

64

cytosine

N

N

NH2

OH

NH

N

O

O

thymine

NH

N

O

O

uracil

Pyrimidines

H HTBin RNA

652. DNA structurea. double-stranded helixb. sugar-phosphate backbone *sugar = deoxyribosec. nucleotide bases pair through hydrogen bonds between the helical strandsd. the sequence of the bases is the "primary structure"

66c. nucleotide base pairingThe most stable complementary DNA base pairing pattern is called "Watson-Crick base pairing" where A=T and GC

Two H-bonds between T and A

H-NN

O

ON

NN

N

N

H

HH

67c. nucleotide base pairing

Three H-bonds between G and C

N

NNH

N N-HH

H

O

guanine cytosine

NN

H-N-H

O H

68

DNA carries genetic information in the sequence of the bases.

DNA mRNA protein

d. DNA sequence (primary structure)

transcription

translation

AAA… UUU…

(an amino acid)

phenylalanine

693. RNA structure• RNA is usually single stranded (ssRNA)• ribose instead of deoxyribose• uracil instead of thymine

ssRNAintramolecular base pairing RNA stem-loop

• primary structure = the base sequence • secondary structure = complementary base pairing in a single RNA molecule• G C A = U

70RNA secondary structureA-G-A-C-A-A-A-C-C-G-U-C-A

RNA stem loopA - -A

C G A UG C

A

A ACC

e.g. tRNA stem loops

71Functions of the major RNAs

1. messenger RNAs (mRNA) contain genetic information to encode a protein

3. ribosomal RNAs (rRNA) are structural and catalytic component of ribosomes, the protein-synthesizing machinery of cells

2. transfer RNAs (tRNA) act as adapters between the mRNA nucleotide code and amino acids during protein synthesis

phe

DNA

mRNA

72D. Proteins1. general structure2. the 21 amino acids3. peptide bonds4. levels of protein structure5. stereoisomers

73D. Proteinslinear chains of L-amino acids linked by peptide bonds

met leu his val glu asn asp cys

peptide bond

e.g. enzymes, transport proteins, antibodies insulin, structural proteins, regulatory proteins, hair, flagella, viral protein coat

741. General structure of L-amino acids

O C – OH

H2N – C – H R O

C – O-

H3N – C – H R

at pH 7

+

carboxylic acidaminogroup

R-group orside chain

-carbon

752. The 21 amino acids encoded by DNA

ACIDICaspartateglutamate

BASIC lysine

arginine histidine

POLAR, NEUTRALserinethreoninetyrosine

asparagine glutaminecysteineselenocysteine

NONPOLAR (HYDROPHOBIC)glycinealaninevaline

phenylalaninetryptophanproline

leucineisoleucinemethionine

76Hydrophobic amino acids tend to be associated with hydrophobic environments • membranes • inside of proteins

Hydrophilic amino acids are often in contact with water Lysozyme

77

aspartate (asp) glutamate (glu)

O C - O-

H3N - C - H CH2

COO-

O C - O-

H3N - C - H CH2

CH2

COO-

+ +

a. Acidic amino acids net negative charge at pH 7

TB

78

lysine (lys) arginine (arg) histidine (his)

b. Basic amino acids:

CH2

CH2

CH2

CH2

NH3+ NH2H2N

CH2

CH2

CH2

C

NH

+

CH2

NNH+

H

net positive charge at pH 7

TB

79c. Polar but neutral

CH2

OHCH- CH3

OH

CH2

OH

CH2

SH

Ser (S) Thr (T) Tyr (Y) Cys (C)

TB

80

CNH2

O

CH2

CNH2

O

CH2

SeH

Asn (N) Gln (Q) Sec (U)

CH2

CH2

c. Polar but neutral (contd.)

TB

81d. Nonpolar (hydrophobic)

CH3

CHCH3H3C

CH2

CHCH3H3C

H

Gly(G) Ala (A) Val (V) Leu (L) Ile (I)

CH

CH2

CH3

CH3

TB

82

CHC

OOH

HN

CH2

CH2

CH2

CH2

NHCH2

CH2

CH2

CH3

S

Pro (P) Trp (W) Phe (F) Met (M)

d. Nonpolar (hydrophobic)

TB

83

O C - O-

H3N - C - H CH2

S

O C - O-

H3N - C - H CH2

S

disulfide bridges antibody

Disulfide bridge covalent bond between two sulfhydryl groups (eg. of cysteines)

+ +

84

O C - O-

H3N - C - H CH2

SeH

selenocysteine: the 21st amino acid

• found in some microbial enzymes like hydrogenase

+

853. Peptide bonds join L-amino acids in proteins

O C - OH

H2N - C - H R1

O C

H2N - C - H R1

O H C - OH N - C - H

R2

O C - OH

H -N - C - H R2

H

H2 O

peptide bond

dehydration

864. Levels of protein structure

a. Primary (1°) structure amino acid sequence

met leu his val glu asn asp cys

87b. Secondary (2°) structurePatterns of folding due to hydrogen bonds between groups of the peptide backbone

-helix -sheet

881. alpha helix (coil)

H

NCHC

O

RH

NCHC

O

RH

NCHC

O

R

H

NCHC

O

RH

NCHC

O

RH

NCHC

O

R

892. beta sheetN

CC

C

O

N

R

R

H

O C

N

CC

C

O

N

R

R

H

O C

H

N

CC

C

O

N

R

R

H

O C

N

CC

C

O

N

R

R

H

O C

H

90c. Tertiary (3°) structureNative 3-D structure of a protein

Stabilized by H-bonds, hydrophobic interactions, van der Waals forces,covalent disulfide bridges, and some ionic bonds

ribonucleasehexokinase

91d. Quaternary (4°) structureassociation of two or more polypeptides

hemoglobin

-chains

-chains

925. StereoisomersMirror-image compounds with the same molecular formula

COOHH2N - C - H

CH3

L-alanine

COOHH - C - NH2

CH3

D-alanine

93Why is this important?

In biology, D-sugars predominate L-amino acids are found in proteins D-amino acids are less common, but are found in bacterial cell walls and antibiotics

94The 4 major cellular macromolecules*:chains (polymers) of repeating units

*Important recurring theme

polysaccharide sugars cell wall glycosidic

lipid fatty acids or membranes ester or ether isoprenoids

nucleic acid nucleotides DNA, RNA phosphodiester

protein amino acids enzymes peptide

polymer monomer example covalent bond(see notes for other examples)

95Study objectives1. Contrast saturated and unsaturated fatty acids. Understand how and why they influence membrane fluidity. Know the general structure of membrane lipids. Know the names of the fatty acids and lipids presented in class. You do NOT need to memorize the structure of the individual fatty acids, ethanolamine, or serine. 2. Compare and contrast bacterial,eukaryal, and archaeal lipids, especially the molecular components and the bonds. More details later.3. What are nucleic acids? Understand that nucleotides are composed of a nitrogenous base (purine or pyrimidine), a sugar (ribose or deoxyribose), and one to three phosphates. Know the structure of the phosphodiester bond. What parts of the nucleotides are connected by the phosphate of the phosphodiester bond? What is meant by the 5' and 3' ends of DNA and RNA?4. Memorize the structure of the nucleotide ATP. This is a very important molecule and we will discuss it in great detail throughout the semester. 5. Know the purines and pyrimidines. Know the number of rings in each. What is the structural difference between thymine (T) and uracil (U)?