MSB 100: Basics of Biomedical Sciences

TOPIC:

•CARBOHYDRATE CHEMISTRY•NUCLEIC ACID CHEMISTRY

Lecturer: Dr. G. Kattam Maiyoh

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Introduction

• Carbohydrates are one of the FOUR major

classes of biological molecules.

• Carbohydrates are also the most abundant biological molecules.

• Carbohydrates derive their name from the

general formula Cn(H2O)~ hydrated carbon or hydrates of carbon

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•Carbs•Proteins •Lipids•NA

functions• Variety of important functions in living

systems: – nutritional (energy storage, fuels,

metabolic intermediates)

– structural (components of nucleotides, plant and bacterial cell walls, arthropod exoskeletons, animal connective tissue)

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–Informational (cell surface of eukaryotes -- molecular recognition, cell-cell communication)

–Osmotic pressure regulation (bacteria)

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In molecular terms

• Carbohydrates are carbon compounds that contain large quantities of hydroxyl groups.

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In chemical terms Carbohydrates are chemically

characterized as:

• Poly hydroxy aldehydes or

• Poly hydroxy ketones.

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Aldoses vs Ketoses

• Sugars that contain an aldehyde group are called Aldoses.

• Sugars that contain a keto group are called Ketoses.

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classificationAll carbohydrates can be classified as either:– Monosaccharides– Disaccharides– Oligosaccharides – Polysaccharides.

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• Monosaccharides - one unit of carbohydrate

• Disaccharides - Two units of carbohydrates.

• Anywhere from three to ten monosaccharide

units, make up an oligosaccharide.

• Polysaccharides are much larger, containing

hundreds of monosaccharide units.

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Complexes

• Carbohydrates also can combine with lipids to form glycolipids

OR

• With proteins to form glycoproteins / proteoglycans.

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Isomers• Isomers are molecules that have the same

molecular formula, but have a different arrangement of the atoms in space. (different structures).

• For example, a molecule with the formula AB2C2, has two ways it can be drawn:

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Isomer 1

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Isomer 2

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Examples of isomers:

1. Glucose

2. Fructose

3. Galactose

4. Mannose

Same chemical formula C6 H12 O6

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EPIMERS

• EPIMERS are sugars that differ in configuration at ONLY 1 POSITION.

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• Examples of epimers : – D-glucose & D-galactose (epimeric at

C4) – D-glucose & D-mannose (epimeric at C2) – D-idose & L-glucose (epimeric at C5)

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Epimer set 1

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Epimer set 2

ENANTIOMERS

Non-Superimposable COMPLETE

mirror image (differ in configuration

at EVERY CHIRAL CENTER.

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The two members of the pair are designated as D and L forms.

In D form the OH group on the asymmetric carbon is on the right.

In L form the OH group is on the left side.

For e.g: D-glucose and L-glucose are enantiomers:

Features of Enantiomers

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A pair enantiomers are mirror images of each other

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Asymmetric carbon in sugars

• A carbon linked to four different atoms or

groups farthest from the carbonyl carbon

• Also called Chiral carbon

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Cyclization of sugars• Less then 1%of CHO exist in an open chain

form (AKA: straight chain, fischer projection, linear form)

• Predominantly found in ring form (AKA: Close, cyclic, Haworth)

• For 6 Carbon sugars, involves reaction of C-5 OH group with the C-1 aldehyde group or C-2 of keto group (carbonyl carbon).

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Ring forms

• Basically 2 types• Six membered ring structures are called

Pyranoses .

• Five membered ring structures are called Furanoses .

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Pyran ring

Furan ring

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Anomeric carbon

• The carbonyl carbon after cyclization becomes the anomeric carbon.

• This creates α and β configuration.

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• Such α and β configuration are called diastereomers and they are not mirror images.

Enzymes can distinguished between these two forms:

• Glycogen is synthesized from α-D glucopyranose

• Cellulose is synthesized from β -D glucopyranose

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MUTAROTATION• Unlike the other stereoisomeric forms, α

and β anomers spontaneously interconvert in solution.

• This is called mutarotation.

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Optical Activity• When a plane polarized light is passed through a

solution containing monosaccharides the light will either be rotated towards right or left.

• This rotation is because of the presence of asymmetric carbon atom.

• If it is rotated towards left- levorotatory (-) (L)

• If it is rotated towards right- dextrorotatory (+) (D)

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Reducing sugar

• Sugars in which the oxygen of the anomeric carbon is free and not attached to any other structure, such sugars can act as reducing agents and are called reducing sugars.

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Polysaccharides

2 types: – HOMOpolysaccharides (all 1 type of monomer), e.g.,

glycogen, starch, cellulose, chitin

– HETEROpolysaccharides (different types of monomers), e.g., peptidoglycans, glycosaminoglycans

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Functions of polysaccharides:

– Glucose storage (glycogen in animals & bacteria,

starch in plants)

– Structure (cellulose, chitin, peptidoglycans,

glycosaminoglycans

– Information (cell surface oligo- and polysaccharides,

on proteins/glycoproteins and on lipids/glycolipids)

– Osmotic regulation

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• Starch and glycogen – Function: glucose storage

Starch -- 2 forms:

• amylose: linear polymer of a(1-> 4) linked glucose residues

• amylopectin: branched polymer of a(1-> 4) linked glucose residues with a(1-> 6) linked branches

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Key examples of polysaccs;

– Glycogen: • branched polymer of a(1-> 4) linked glucose

residues with a(1-> 6) linked branches • like amylopectin but even more highly branched

and more compact

• branches increase H2O-solubility

– Branched structures: many nonreducing ends, but only ONE REDUCING END (only 1 free anomeric C, not tied up in glycosidic bond)

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• Each molecule, including all the branches, has only ONE free anomeric C

– single free anomeric C = "reducing end" of polymer

– the only end capable of equilibrating with straight chain form of its sugar residue, which has free carbonyl C.

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Which can then: – REDUCE (be oxidized by) an oxidizing

agent like Cu2+

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• Cellulose and chitin

– Function: STRUCTURAL, rigidity important

Cellulose: • Homopolymer, b(1-> 4) linked glucose residues • Cell walls of plants

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Chitin:

• Homopolymer, b(1-> 4) linked N-acetylglucosamine residues

• hard exoskeletons (shells) of arthropods (e.g., insects, lobsters and crabs)

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Nucleic acids• Nucleic acids are polymeric macromolecules, or

large biological molecules, essential for all known forms of life.

• Nucleic acids, which include DNA (deoxyribonucleic acid) and RNA (ribonucleic acid), are made from monomers known as nucleotides.

• Each nucleotide has three components: a 5-carbon sugar, a phosphate group, and a nitrogenous base.

• If the sugar is deoxyribose, the polymer is DNA. • If the sugar is ribose, the polymer is RNA.

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Nucleic Acids

DNA –deoxyribonucleic acid

– Polymer of deoxyribonucleotide

triphosphate (dNTP)

– 4 types of dNTP (ATP, CTP, TTP, GTP)

NB: All made of a base + sugar +

triphosphate

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RNA –ribonucleic acid – Polymer of ribonucleotide triphosphates

(NTP)– 4 types of NTP (ATP, CTP, UTP, GTP)

NB: All made of a base + sugar + triphosphate

So what’s the difference?

• The sugar (ribose vs. deoxyribose) and one base (UTP vs. TTP)

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Deoxyribose (like ribose) is a sugar with 5 carbon atoms in a ringOxygen is one of the ring members In Deoxyribose, one of the OH groups is missing and replaced with hydrogen, Thus deoxy = - 1 oxygen

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Phosphate groups are important because they link the sugar on one nucleotide onto the phosphate of the next nucleotide to make a polynucleotide.

• Nitrogenous bases

• In DNA the four bases are:– Thymine– Adenine– Cytosine– Guanine

• In RNA the four bases are:– Uracil– Adenine– Cytosine– Guanine

Base - pairing

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DNA and RNA are polynucleotides

• Both DNA and RNA are polynucleotides.• They are made up of smaller molecules

called nucleotides.

• DNA is made of two polynucleotide strands:

• RNA is made of a single polynucleotide strand:

Nucleotide Nucleotide

Nucleotide

Nucleotide

Nucleotide

Nucleotide

Nucleotide

Nucleotide Nucleotide Nucleotide Nucleotide

NucleotideNucleotide Nucleotide

Nucleotide

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Nucleotide

DNA •Information for all proteins stored in DNAin the form of chromosomes or plasmids. •Chromosomes (both circular and linear) consist of two strands of DNA wrapped together in a left handed helix.(imagine screwing inwards)

•The strands of the helix are held together by hydrogen bonds between the individual bases. •The “outside” of the helix consists of sugar and phosphate groups, giving the DNA molecule a negative charge.

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BASES

The Rule: Complimentarity• Adenine always base pairs with Thymine

(or Uracil if RNA)

• Cytosine always base pairs with Guanine.

• This is because there is only exactly enough room for

one purine and one pyrimidine base between the two

polynucleotide strands of DNA/RNA (see next slide).

• These bases are said to be complimentary to each other

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Complimentary Base Pairs

A-T Base pairing G-C Base Pairing

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DNA Structure

– The DNA helix is “anti-parallel” – Each strand of the helix

has a 5’ (5 prime) end and

a 3’ (3 prime) end.

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Central Dogma• Replication

– DNA making a copy of itself• Making a replica

• Transcription– DNA being made into RNA

• Still in nucleotide language

• Translation– RNA being made into protein

• Change to amino acid language

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Replication• Remember that DNA is self complementary

• Replication is semiconservative– One strand goes to next generation– Other is new

• Each strand is a template for the other– If one strand is 5’ AGCT 3’– Other is: 3’ TCGA 5’

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Replica – Learning check

• Write the strand complementary to:

3’ ACTAGCCTAAGTCG 5’

Answer

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• Both processes use DNA as the template.

• Phosphodiester bonds are formed in both cases.

• Both synthesis directions are from 5´ to 3´.

Similarity between replication and transcription

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replication transcription

template double strands single strand

substrate dNTP NTP

primer yes no

Enzyme DNA polymerase RNA polymerase

product dsDNA ssRNA

base pair A-T, G-C A-U, T-A, G-C

Differences between replication and transcription

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Ribonucleic acid (RNA)

• Almost all single stranded (exception is RNAi).

• In some RNA molecules (tRNA) many of the bases

are modified (e.g. psudouridine).

• Has capacity for enzymatic function -ribozymes

• One school of thought holds that early organisms

were based on RNA instead of DNA (RNA world).

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RNA

• Several different “types” which reflect different functions

– mRNA (messenger RNA)

– tRNA (transfer RNA)

– rRNA (ribosomal RNA)

– snRNA (small nuclear RNA)

– RNAi (RNA interference)

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RNA function

• mRNA – transfers information from DNA to ribosome (site where proteins are made)

• tRNA – “decodes” genetic code in mRNA, inserts correct A.A. in response to genetic code.

• rRNA-structural component of ribosome• snRNA-involved in processing of mRNA• RNAi-double stranded RNA, may be

component of antiviral defense mechanism.

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