Ch. 8: Carbohydrates Ch. 10: Metabolism (intro) Ch. 11: Glycolysis Ch. 12: Other pathyways in carbo. metabolism Exam: Tues Mar 2nd Diseases associated with sugar metabolism 4 major classes of biomolecules Proteins Carbohydrates Fats Nucleic acids

Most abundant class of macromolecules on the earth Ch. 8: Carbohydrates Glucose

Carbohydrate (a.k.a. sugars, saccharide) –(CH 2 O) n n>3 – Monosaccharide – smallest unit or ‘building blocks’ – Oligosaccharide - disaccharide –Polysaccharide – (more than 20) Glycoconjugates - linked to protein or lipid (2-20) Function Energy storage and release Cell wall and protective coatings Marker mol. on cell surface cell-cell interactions virus invasion… Protein function (covalent modification) DNA/RNA ‘Hydrate of carbon’

Polyhydroxyl aldehyde (aldose) or Polyhydroxyl ketone (ketose) –Aldotriose Glyceraldehyde (D or L) –Ketotriose Dyhydroxyacetone D enantiomer predominate in natureMonosaccharides (CH 2 O) 3

Monosaccharides - Aldoses # Isomers = 2 n where n = # of chiral carbons Epimers – differ in configuration at only one chiral carbon Enantiomer Distant chiral C From most oxidized Not all made in nature

Monosaccharides - Ketoses # Isomers = 2 n where n = # of chiral carbons

Furanose – 5 membered ring, one member O of –OH Pyranose – 6 membered ring, one member O of –OH Cyclization - Ring Structures Similar to: Optical behavior of monosaccharides in solution suggests that they have an additional chiral center.

Cyclization of Monosaccharides Most oxidized C New chiral C

Cyclization - aldohexose Draw most oxidized carbon (C1 aldose and C2 ketose) on right and number C clockwise In ring most oxidizes carbon new chiral center (anomeric C) Transfer information from Fisher projections -OH on right then down in Haworth -OH on left then up in Haworth Bulky substituent on highest numbered carbon points up rapid equilibrium Anomers

Equilibrate in solution In solution at 31°C –64%  -D-glucopyranose –36%  -D-glucopyranose –Very little in open chain or furanose form Cyclization - aldohexose Anomers

Hemiacetal Cyclization - aldopentose Haworth projection Anomers Equilibrium Anomeric C

“Furanose” Conformations Not planar Rapidly interconvert

“Pyranose” Conformations More stable Whether a ring substituent is Equatorial (same plane) or Axial (above/below) depends on whether C-1 or C-4 is above the ring.

Derivatives of monosaccharides – sugar phosphates Important in metabolism alcohol phosphate esters hemiacetal phosphate More reactive Nucleic acid metabolism Energymetabolism

Derivatives of monosaccharides – deoxy sugars replacement of one of the -OH groups with H Important in DNA

DNA RNA OH

RNA hydrolysis

Derivatives of monosaccharides – amino sugars amino groups or an acetylated amino group replaces one of the -OH groups NeuNAc Sialic acids: on cell surface glycoproteins

Derivatives of monosaccharides – sugar alcohols reduction of carbonyl oxygen, so polyhydroxyl alcohol Id glyceraldehyde Idose ---- Inositol

derived from aldoses by either the oxidation of C1 or the highest-numbered carbon Glucose oxidation : gluconate or glucuronate gluconate can cyclize under acidic conditions to form a lactone - intramolecular ester. Derivatives of monosaccharides – sugar acids

Vitamin C or L-Ascorbic Acid Primates unable to do this reaction

Common Carbohydrates and their abbreviations

Glycoside Bonds – acetal linkage between the anomeric carbon of a sugar and an alcohol, an amine, or a thiol Compounds containing glycoside bonds are called glycosides if glucose donates the anomeric carbon then glucosides

Glycoside Bonds – Disaccharides Hemiacetals -a reactive carbonyl that can be oxidized. reducing non-reducing non-reducing sugar No open chain equil  anomer: refers to free C 1 OH (In equilibruim)

Glycoside Bonds – Disaccharides epimer Most abundant disacc. in nature (plants)

Since mono- and disaccharides are hemiacetals they have a reactive carbonyl that can be oxidized. Linear polymer usually one reducing end (free anomeric carbon), one non-reducing end, and all internal monosaccharides are acetals that are not in equilibrium with open chains form. Some polymers such as the disaccharide sucrose do not have a reducing end (both anomeric carbons are involved in the gycosidic bond) so non-reducing sugar. Glycoside Bonds – Reducing and Non-reducing

Glycoside Bonds – Other

Polysaccharides – Glucose Storage Amylose Amylopectin and Glycogen Plant starch – mixture of amylose and amylopectin Animals glycogen No template (ie no gene) Homoglycans- one type of monosaccharide glucose residues (maltose units) Amylopectin: branch every 25 residues Glycogen: branch every 8-12 residues 10% mass of liver

Polysaccharides -Starch Degradation Humans digest starch via two enzymes: –α -amylase - endoglycosidase of α-(1- 4) linkages (random) – debranching enzyme (cleaves limit dextrans) Higher plants have –β- amylase exoglycosidase of α- (1- 4) linkages, releasing the disaccharide maltose Single reducing end Know how starch is broken down !

Amylose Polysaccharides – Structure Humans don’t have  -glucosidases Microbe that live in ruminants do Plant cell walls, stems and branches ,000 Glc residues 180 deg rotation termites Rigid extended conformation H-bonding Forms bundles or fibrils Cellulose  -(1-4) linkage

Polysaccharides – Structure Chitin –found in exoskeletons of insects and crustaceans, and in cell wall of algae and fungi –composed of β- (1-4)linkage of GlcNAc residues. 2 nd most abundant organic compound on earth 180 deg rotation H-bonding Adjacent strands

Glycoconjugates: Proteoglycans Glycosaminoglycans have dissaccharide components (repeating) –one sugar is an amino sugar; e.g. GalNAc, or GlcNAc. The other sugar is usually a uronic acid Certain types can be sulfated, etc. They are highly hydrated, and viscous and are excellent lubricants Fluid of joints Elastic and resistant to compression cartilage unbranched cartilage heteroglycan

Glycoconjugates: Peptidoglycan Bacteria cell wall, heteroglycans chains linked to peptides GlcNAc linked to N-acetylmuramic acid (MurNAc) joined by β -(1-4) linkage Large/rigid mol Defines shape of cell Gram stain +/-

Glycoconjugates - Glycoproteins O-linked - typically a GalNAc residue linked to the side chain of Ser or Thr, occurs in the golgi N-linked-typically a GlcNAc residue linked to the nitrogen of an Asn, occurs in the endoplasmic reticulum

N-linked Glycoconjugates - Glycoproteins Large amt of structural diversity possible !!

Glycoconjugates - Glycoproteins and blood types

Practice Problems Draw the Fisher projections of fructose and show how it can cyclize to form both the α and β anomers of fructopyranose and fructofuranose. Draw the disaccharide  -D-ribofuranosyl –(1-4)-  -D-glucopyranose. Is this a reducing or nonreducing sugar? Compare and contrast the structures of starch, glycogen and cellulose.