Chapter 26 – Nucleic Acids

Cyclic Structure

Aldehydes and ketones react with alcohols to form hemiacetalshemiacetalscyclic hemiacetals form readily as five- or six-

membered ring

O-HH

O

CO O

H

H

O O-H

H4-Hydroxypentanal

A cyclic hemiacetal

14

14

redraw to show -OH and -CHO

close to each other

Haworth Projectionsaldopentoses also form cyclic hemiacetalsthe most prevalent forms of D-ribose and

other pentoses in the biological world are furanoses

OH ()

H

HOH OH

H HOHOCH2

H

OH ()

HOH H

H HOHOCH2

-D-Ribofuranose(-D-Ribose)

-2-Deoxy-D-ribofuranose(-2-Deoxy-D-ribose)

Formation of Glycosides

Treatment of a monosaccharide with an alcohol gives an acetal

HH OH

HHO

HOH

OH

H

CH2OHO

CH3OHH

+

-H2O

OCH2OH

H

OH

OCH3H

HOH

OHH

H

OCH2OH

H

OH

HH

HOH

OHH

OCH3

(-D-Glucose)-D-Glucopyranose

Methyl -D-glucopyranoside(Methyl -D-glucoside)

anomeric carbon

+

+

Methyl -D-glucopyranoside(Methyl -D-glucoside)

glycosidicbond

Disaccharides

Sucrosemost abundant disaccharide sucrose is a nonreducing sugar (why)

HOOH

OH

CH2OH

O

OH

HOO

CH2OH

HOCH2

OHO

HO

O

OH

CH2OH

OH

HOO

CH2OH

HOCH2

1

1

2

1

2

1

a unit of -D-glucopyranose

a unit of -D-fructofuranose

Composition of Nucleic AcidsNucleic acid: A polymer of nucleotides.Nucleotide: A five-carbon sugar bonded to a

cyclic amine base and a phosphate group.

Glycosides

a cyclic acetal derived of a monosaccharide is called a glycosideglycoside

the bond from the anomeric carbon to the -OR group is called a glycosidic glycosidic bondbond

mutarotation is VERY SLOW in a glycoside

glycosides are stable in water and aqueous base, but like other acetals, are hydrolyzed in aqueous acid to an alcohol and a monosaccharide

DNA and RNA are two types of nucleic acids.In RNA (ribonucleic acid) the sugar is D-ribose. In DNA (deoxyribonucleic acid) the sugar is 2-

deoxyribose. (The prefix “2-deoxy-” means that an oxygen atom is missing from the C2 position of ribose.)Also may be spelled “desoxy ...”

Five heterocyclic amines are found in nucleic acids.

Thymine is present only in DNA molecules (with rare exceptions).

Uracil is present only in RNA molecules.Adenine, guanine, and cytosine are present in

both DNA and RNA.A, G are purines, C, T, and U are pyrimidines

Nucleoside: A five-carbon sugar bonded to a cyclic amine base; a nucleotide with no phosphate group.

Nucleosides are named with the base name modified by the ending –osine for the purine bases and -idine for the pyrimidine bases.

Deoxy- is added to deoxyribose nucleosides. Numbers with primes are used for atoms in the sugar.Nucleotides are named by adding 5’-monophosphate

at the end of the name of the nucleoside.

For example, adenosine 5’-monophosphate (AMP) and deoxycytidine 5’-monophosphate (dCMP).

Nucleotides that contain ribose are classified as ribonucleotides and those that contain 2-deoxy-D-ribose are known as deoxyribonucleotides designated by leading their abbreviations with a lower case “d”.

Phosphate groups can be added to nucleotides to form diphosphate or triphosphate esters. Adenosine triphosphate (ATP) plays an essential role as a source of biochemical energy, which is released during its conversion to adenosine diphosphate (ADP).

The Structure of Nucleic Acid ChainsNucleic acids are polymers of nucleotides.

The nucleotides are connected in DNA and RNA by phosphate diester linkages between the group on the sugar ring of one nucleotide and the phosphate group on the next nucleotide.

The “repeat unit” of the monomer is the sugar ring and phosphodiester unit – because the base changes, we can think of this as a copolymer. The chemistry of the backbone is identical for all of the nucleotides.

GlycerophospholipidsA phosphatidic acid

the fatty acid on carbon 2 is always unsaturated

further esterification with a low-molecular-weight alcohol gives a glycerophospholipid

CH2

CH

CH2-O-P-O-

O

O

O

Oglycerol

palmitic acid

oleic acid

O

O-

Glycerophospholipids

HOHO

OHOH

OH

OH

NH3+

HOCH2CHCOO-

HOCH2CH2N(CH3)3

HOCH2CH2NH2

inositol phosphatidylinositol

Name and FormulaName of Glycerophospholipid

ethanolamine

+choline lecithin

cephalin

serine cephalin

-More often phosphatidyl____________More often phosphatidyl____________

Glycerophospholipidsa lecithin (phosphotidylcholine)a lecithin (phosphotidylcholine)

CH2

CH

CH2

O

O

O

O

O P OCH2CH2N(CH3)3

O

O-

+

palmitic acid

linolenic acid

glycerol

choline

A nucleotide chain commonly has a free phosphate group on a 5’ carbon at one end (known as the 5’ end) and a free –OH group on a 3’ carbon at the other end (the 3’ end).

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A nucleotide sequence is read starting at the 5’ end and identifying the bases in order of occurrence. One-letter abbreviations of the bases are commonly used : A for adenine, G for guanine, C for cytosine, T for thymine, and U for uracil in RNA. The trinucleotide at right would be represented by T-A-G or TAG.

Base Pairing in DNA: Watson-CrickThe double helix resembles a twisted

ladder, with the sugar–phosphate backbone making up the sides and the hydrogen-bonded base pairs, the rungs. The sugar–phosphate backbone is on the outside of this right-handed double helix, and the heterocyclic bases are on the inside, so that a base on one strand points directly toward a base on the second strand.

The two strands of the DNA double helix run in opposite directions, one in the 5’ to 3’ direction, the other in the 3’ to 5’ direction.

-Helix

- Hydrogen bonds are between the C=O of peptide bond Hydrogen bonds are between the C=O of peptide bond and the H-N of another peptide linkage 4 AA’s further and the H-N of another peptide linkage 4 AA’s further along the chain.along the chain.

- Grey = CGrey = C

- Blue = NBlue = N

- Red = ORed = O

- Yellow = Yellow = R-groupR-group

- White = White = HH

Hydrogen bonds connect the pairs of bases; thymine with adenine, cytosine with guanine. Thus a purine always pairs with a pyrimidine. What would happen if not? What would happen if we had C-A or G-T pairs?

The pairing of the bases along the two strands of the DNA double helix is complementary. An A base is always opposite a T in the other strand, a C base is always opposite a G. This base pairing explains why A and T occur in equal amounts in double-stranded DNA, as do C and G. To remember how the bases pair up, note that if the symbols are arranged in alphabetical order the outer 2 and inner 2 pair up.

(a) Notice that the base pairs are nearly to the sugar–phosphate backbones. (b) A space-filling model of the same DNA segment. (c) An abstract representation of the DNA double helix.

DNA, Chromosomes, and GenesWhen a cell is not actively dividing, the

DNA (a polymer of deoxyribonucleic acid) is twisted around proteins called histones – this complex is called chromatin.

During cell division, chromatin organizes itself into chromosomes. Each chromosome contains a different DNA molecule, and the DNA is duplicated so that each new cell receives a complete copy.

Each DNA molecule, in turn, is made up of many genes—individual segments of DNA that contain the instructions that direct the synthesis of a single polypeptide.

The duplication, transfer, and expression of genetic information occurs as the result of three fundamental processes: replication, transcription, and translation.

Replication: The process by which copies of DNA are made when a cell divides.

Transcription: The process by which the information in DNA is read and used to synthesize RNA.

Translation: The process by which RNA directs protein synthesis.

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(a) DNA unwinds, exposing single strands.

(b) Single-stranded DNA is exposed at numerous replication forks as DNA unwinds.

(c) DNA polymerase enzymes facilitate copying of the single-stranded DNA.

DNA polymerase catalyzes the reaction between the 5’ phosphate on an incoming nucleotide and the free 3’ –OH on the growing polynucleotide.

The template strand can only be read in the 3’ to 5’ direction, and the new DNA strand can grow only in the 5’ to 3’ direction.

Only the leading strand grows continuously from 5’ to 3’ towards the fork.

The lagging strand is replicated from 5’ to 3’ in short segments called Okazaki fragments.

These short sections are joined later by DNA ligase.

Two identical copies of the DNA double helix are produced during replication. In each new double helix, one strand is the template and the other is the newly synthesized strand. We describe the result as semiconservative replication (one of the two strands is conserved).

Structure and Function of RNARibosomal RNAs: Outside the nucleus but

within the cytoplasm of a cell are the ribosomes, small granular organelles where protein synthesis takes place. Each ribosome is a complex consisting of about 60% ribosomal RNA (rRNA) and 40% protein, with a total molecular weight of approximately 5,000,000 amu.

The transfer RNAs (tRNA) are smaller RNAs that deliver amino acids one by one to protein chains growing at ribosomes. Each tRNA carries only one amino acid.

The messenger RNAs (mRNA) carry information transcribed from DNA. They are formed in the cell nucleus and transported out to the ribosomes, where proteins will be synthesized. These polynucleotides carry the same code for proteins as does the DNA.

Transcription: RNA SynthesisOnly one of the two DNA strands is

transcribed during RNA synthesis. The DNA strand that is transcribed is the template strand; its complement in the original helix is the informational strand.

The mRNA molecule is complementary to the template strand, which makes it an exact RNA-duplicate of the DNA informational strand, with the exception that a U replaces each T in the DNA strand.

The transcription process begins when RNA polymerase recognizes a control segment in DNA that precedes the nucleotides to be transcribed.

The sequence of nucleic acid code that corresponds to a complete protein is known as a gene.

The RNA polymerase moves down the DNA segment to be transcribed, adding complementary nucleotides one by one to the growing RNA strand as it goes.

Transcription ends when the RNA polymerase reaches a codon triplet that signals the end of the sequence to be copied.

Some of these bases, however, do not code for genes. It turns out that genes occupy only about 10% of the base pairs in DNA

The code for a gene is contained in one or more small sections of DNA called an exon.

The code for a given gene may be interrupted by a sequence of bases called an intron. Introns are sections of DNA that do not code for any part of the protein to be synthesized.

The initial mRNA strand contains both exons and introns, and is known as heterogeneous nuclear RNA (or hnRNA).

In the final mRNA molecule released from the nucleus, the intron sections have been cut out and the remaining pieces are spliced together through the action of a structure known as a spliceosome.

The Genetic Code Codon: A sequence of three ribonucleotides in the

messenger RNA chain that codes for a specific amino acid; also a three-nucleotide sequence that is a stop codon and stops translation.

Genetic code: The sequence of nucleotides, coded in triplets (codons) in mRNA, that determines the sequence of amino acids in protein synthesis.

Of the 64 possible three-base combinations in RNA, 61 code for specific amino acids and 3 code for chain termination.

A codon is the triplet sequence in the messenger RNA (mRNA) transcript which specifies a corresponding amino acid (or a start or stop command). An anticodon is the corresponding triplet sequence on the transfer RNA (tRNA) which brings in the specific amino acid to the ribosome during translation. The anticodon is complementary to the codon, that is, if the codon is AUU, then the anticodon is UAA. (No T (Thymine) in mRNA. It's replaced by U (Uridine). )

Translation: Transfer RNA and Protein Synthesis

Overview: The codons of mature mRNA are translated in the ribosomes, where tRNAs deliver amino acids to be assembled into proteins (polypeptides).

The three stages in protein synthesis are initiation, elongation, and termination.

Just like there can be many replication forks, more than one ribosome can attach to long mRNA, and translate more than one copy of the protein at once.

Structure of tRNA. (a) The cloverleaf shaped tRNA contains an anticodon triplet and a covalently bonded amino acid at its 3’ end.

Notice that ssRNA can base pair to form hydrogen-bonded stretches. These sections stabilize the tRNA’s folded structure making the codon and AA available for binding and reaction.

Initiation: Protein synthesis begins when an mRNA, the first tRNA, and the small subunit of a ribosome come together.

The first codon on the end of mRNA, an AUG, acts as a “start” signal for the translation machinery and codes for a methionine carrying tRNA. In some organisms this is “fmet” – N-formylmethionine. fMet is found only as AA 1 in proteins (if it is found).

Initiation is completed when the large ribosomal subunit joins the small one and the methionine-bearing tRNA occupies one of the two binding sites on the united ribosome.

If it is not needed, the methionine from chain initiation is removed by post-translational modification before the new protein goes to work.

The three elongation steps now repeat:

The next tRNA binds to the ribosome.

Peptide bond formation attaches the new amino acid to the chain and the first tRNA is released.

Ribosome position shifts to free the second binding site for new tRNA.

Termination: A “stop” codon signals the end of translation. An enzyme called a releasing factor then catalyzes cleavage of the polypeptide chain from the last tRNA. The tRNA and mRNA molecules are released from the ribosome, and the two ribosome subunits again separate.