1. GUTS session on carbohydrates and glycolipids Dr. Arrel Toews (say Tavz, like “waves”) 420 ME Jones Building atoews@med.unc.edu 843-8727 A primer on carbohydrate and glycolipid structure, nomenclature, properties, and general functions See also the GUTS carbohydrate/glycolipid notes (.doc) - self-assessment exam - additional information

2. OXIDATION STATES OF CARBON: You better know!! oxidation OXIDATION: - loss of e - - loss of H - gain of O reduction REDUCTION: (just the opposite) - gain of e - - gain of H - loss of O saturated alcohol aldehyde ketone carboxylic carbon hydrocarbon acid dioxide H H O O O l ll ll ll R-C-H R-C-OH R-C-H R-C-R -C-OH O=C=O ll H carbohydrates fats

3. SUGARS – CARBOHYDRATES - “hydrates of carbon” Sugars - polyalcohols (-OH) + aldehyde = aldose or + ketone = ketose Simple sugars – monosaccharides 2 sugars – disaccharides sugar polymers - polysaccharides Need for: - energy fuel - energy storage - cell membranes/walls - cell-cell interactions General formula: (CH 2 O) n

4. Fischer projection OH H-C l H-C-OH l HO-C-H l H-C-OH l C l CH 2 OH O 1 6 5 4 3 2 C1  Open-chain structure O H-C l H-C-OH l HO-C-H l H-C-OH l H- C-OH l CH 2 OH 1 6 5 4 3 2 Various ways to visualize the structure of glucose H OH H H HO HOCH 2 H OH H O 1 6 5 4 32 Ring structure (Haworth projection) Shorthand method of drawing sugar structures ( l = OH; C & H understood) O O CH 2 OH Space-filling model

5. Constantly opening/closing but prefers ring  =  =   =  =  C1-OH Glucose (open-chain form) - OH on C5 links to C1 (aldehyde C) - C1 changes from aldehyde to alcohol - 6-sided (5-C, 1-O) ring forms This is important for glycosidic links (hooking sugars together) Glucose likes to form a ring in solution  -glucose  -glucose O H-C l H-C-OH l HO-C-H l H-C-OH l H- C-OH l CH 2 OH 1 6 5 4 3 2 H OH H HO HOCH 2 H OH H 6 5 4 32 H C O 1 OH H H H HO HOCH 2 H OH H O 1 6 5 4 32 H H H HO HOCH 2 H OH H O 1 6 5 4 32

6. fructose - OH on C5 links to C2 (ketone C) - C2 changes from ketone to alcohol - 5-sided (4-C, 1-O) ring forms Fructose likes to form a ring too!!  =  =   =  =  C2-OH  -fructose (ring form) H 2 -C-OH l C O l HO-C-H l H-C-OH l H- C-OH l CH 2 OH 1 6 5 4 3 2 2 CH 2 OH l C O H HOCH 2 OH 5 H H HO Constantly opening/closing but prefers ring H HO HOCH 2 OH 5 CH 2 OH OH 2 O H H

7. sugar + ATP sugar~P + ADP - Sugar~P are “primed for metabolism” – extra energy - Key intermediates in: - energy production - biosynthesis Phosphorylated sugars are “activated intermediates” dihydroxyacetone-P glyceraldehyde-P glucose-6-P kinase O - l - O-P O l O l CH 2 H OH H H HO H OH H O 6 O - l - O-P O l O l CH 2 l H-C-OH l C H O O - l - O-P O l O l CH 2 l C O l CH 2 OH

8. N-glycosidic links (C-N bonds) are important too Adenosine (the A in ATP) Ribose D- glucosamine (an amino-sugar) H OH H H HO HOCH 2 H OH H O NH 3 + H OH HOCH 2 H O 1 5 4 2 H OH H H H HOCH 2 H O H OH H D -ribose (ATP, RNA) 2-deoxyribose (DNA) Important pentoses 3 2 H OH HOCH 2 H O H H OH NH 2 C N N C HC C NN CH Adenine

9. Disaccharides – 2 sugars joined by glycosidic link H OH H H HO HOCH 2 H OH H H H H HO HOCH 2 H OH 1 6 5 4 32 C1  H OH H H HO HOCH 2 H OH H 1 6 5 4 32  -glucose glucose OH O O HOH hydrolysis Hydrolysis (breaking a bond by adding water across it) of glycosidic links regenerates sugar monomers Formation of a glycosidic link locks C1 into specific configuration (either  or  ). It CANNOT open or close anymore!! This matters a lot, especially for di/polysaccharides Maltose glucose(  -1,4)glucose H H OH H HO HOCH 2 H OH H H H H HOCH 2 H OH 1 6 5 4 32 H H H HOCH 2 H OH H 1 6 5 4 32 H H H HOCH 2 H OH 14 32 O HOH condensation Glycosidic links between sugar monomers are formed by condensation (dehydration) reactions OO

10. Disaccharides – 2 sugars joined by glycosidic link Sucrose (fruit sugar) glucose + fructose Cellobiose glucose(  1  4)glucose  -glycosidic link (C1-OH is  ) OH H H H HO HOCH 2 H OH H O 1 H H H HOCH 2 H OH H O 1 4 O Lactose (milk sugar) galactose(  1  4)glucose  -glycosidic link H OH HOCH 2 H OH H H HOCH 2 H OH 1 6 5 4 32 H H H HOCH 2 H OH H 1 6 5 32 H H H HOCH 2 H OH 14 32 O HO H H O O

11. Important glucose polymers AMYLOSE (starch in plants) long linear chains (  1  4 links in chains with  1  6 links at branches) AMYLOPECTIN (starch in plants) & GLYCOGEN (animals) branched chains 14 1 6 14 (  1  4 links) 14 (  1  4 links) CELLULOSE (in plants) long linear chains 14

12. Glycosaminoglycans (GAGs) aka mucopolysaccharides long chains of disaccharide-repeat units - acidic sugar (- charge) - acetylated amino sugar (no charge) Important components of: - extracellular matrix - synovial fluid of joints - mucus - vitreous humor of eye Proteoglycans – proteins with lots of GAG chains attached

13. Glucuronate N-acetyl- (acidic) glucosamine Repeating disaccharides in hyaluronic acid O COO - OH O O O CH 2 OH NH-C-CH 3 ll O HO............. An example of glycosaminoglycan (GAG) repeat units Don’t worry about the structures; just note the (-) charge (repeat) Acetylation of NH 2 group (otherwise present as NH 3 + ) prevents protonation, so no (+) charge present

14. Other GAGs have even more (-) charges! O COO - OH O O O CH 2 OH NH-C-CH 3 ll O HO............. (repeat) Sulfate (SO 4 = ) groups on various –OH (and to variable degrees) in other GAGs. Sulfation makes them even more negative SO 4 =

15. Structures and properties are generally similar to phospholipids (amphipathic) Phospholipids Sphingolipids F A T T Y A C I D O (usually) Long-chain amino alcohol (sphingosine) sugar(s) polar head long hydrophobic tail Remember Sphingolipids?? (Glyco)

16. base molecule is sphingosine (in black above) long-chain fatty acid (several different ones) O NH C F A T T Y A C I D X O OH A primer on sphingolipid nomenclature (trans) S p h i n g o s i n e if X = H, the molecule is ceramide (base of all sphingolipids) if X = galactose, the molecule is cerebroside (galactosyl-ceramide, an important myelin lipid) if X = galactose-sulfate, the molecule is sulfatide (also a myelin component) if X = glucose, the molecule is glucosyl-ceramide (precursor to gangliosides, globosides) if X = P -choline, the molecule is sphingomyelin

17. Vocabulary – do you know the meaning of the following terms? oxidation vs reduction sugars mono-, di-, and polysaccharides glucose fructose lactose sucrose glycogen starch (amylose and amylopectin) glycosaminoglycan (mucopolysaccharide) proteoglycan sphingolipid sphingosine ceramide sphingomyelin cerebroside (and sulfatide)