Today’s topics: Carbohydrate chemistry polyhydroxy aldehyde/ketones

1. Today’s topics: Carbohydrate chemistry polyhydroxy aldehyde/ketones chirality and optical isomers – diatereomers & enantiomers hemiacetals and anomers – the cyclic forms of sugars acetals and glycosidic bonds – disaccharides to polysaccharides • Allosteric enzymes ……. • Have two distinct folded conformations • Have quaternary structure • Have a sigmoidal v vs. [S] plot • all of the above • Allosteric enzymes ……. • Can only be turned on one time • Can be regulated only to decrease activity • Require an ‘activating’ enzyme. • Can have incremental alterations in activity.

2. [E] = 1 x 10-6 M v = kcat • [ES] vmax = kcat • [E] kcat = vmax/[E] = 270 s-1 kcat /KM= 3.6 x 104 M-1s-1 not diffusion limited

3. C3H6O3 or… C3(H2O)3 Opposite amino acids, nature typically makes only D carbohydrates. CH = O | CH — OH | CH2— OH

4. A carbohydrate is a polyhydroxy aldehyde or ketone and their derivatives (e.g. hemiacetals) Although initially named for having the general formula Cn(H2O)n, this is no longer required for something to be classified a carbohydrate. Name some carbohydrates. Carbohydrates you might be familiar with include: sugars (monosaccharides) like glucose, and fructose. Disaccharides like sucrose, maltose, and lactose …. Polysaccharides like starch, glycogen, and cellulose.

5. Monosaccharides 3-carbon or triose 4-carbon or tetrose 6-carbon hexose # optical isomers = 2n 5-carbon pentose

6. H H CH2 - OH | C= O | HO - C - H | H - C - OH | H - C - OH | CH2 - OH C=O | H - C - OH | HO - C - H | H - C - OH | H - C - OH | CH2 - OH C=O | H - C - OH | HO - C - H | HO - C - H | H - C - OH | CH2 - OH Fructose Glucose Galactose C6H12O6 Does glucose exhibit optical isomerism? a) yes b) no How many chiral carbons? a) 1 b) 2 c) 4 d) 6

7. Diastereomers Optical isomers that are not mirror images of each other.

8. H H C=O | H - C - OH | HO - C - H | H - C - OH | H - C - OH | CH2 - OH C=O | HO - C - H | H - C - OH | HO - C - H | HO - C - H | CH2 - OH L- Glucose D- Glucose Enantiomers Optical isomers that are mirror images of each other. All natural sugars are D isomers

9. Hemiacetals and Hemiketals

10. H b – D - Glucose C=O | H - C - OH | HO - C - H | H - C - OH | H - C - OH | CH2 - OH OH OH OH OH OH OH O O OH OH OH D- Glucose OH a – D - Glucose Anomers

11. b– D - Galactose b – D - Glucose OH OH OH OH OH OH OH OH OH OH OH O O O O OH OH OH OH a– D - Glucose Diastereomers optical isomers that aren’t mirror images Anomers – diasteromers that interchange in solution OH OH OH OH Enantiomers the optical isomer that is the mirror image OH L - Glucose

12. a – D - Glucose OH OH OH OH O O O O OH OH OH OH O OH OH OH OH OH OH OH OH OH OH maltose – a – 1,4 glycosidic bond

13. Lactose (milk sugar)Galactose + Glucose -1,4 OH O OH OH O OH O HO OH OH OH

14. Sucrose (Table Sugar) OH OH OH O 1 HO OH O O HO 2 - 1, - 2 OH OH

15. Common Polysaccharides Chitin N-acetylglucosamineb-1,6 insect exoskeleton & fungal cell walls Cellulose Glucose - b-1,6 Plant cell walls Starch Amylose: glucose a-1,4 Amylopectin: glucose a-1,4 & a-1,6 Plant glucose storage Glycogen Glucose - a-1,4 & a-1,6 Animal glucose storage

16. OH OH OH O O O OH OH OH HO OH OH OH O O O Polysaccharides Cellulose : Plant cell walls Chitin ― insect exoskeleton & fungal cell walls Starch : Plant glucose storage Glycogen : Animal glucose storage Starch& glycogenstore glucose in plants& animals. They contain mostly a-1,4 glycosidic bonds. etc.

17. OH OH OH O O O OH OH OH OH OH OH O O O etc. Cellulose ― b-1,4 Linkage

18. a-1,4 a-1,6 OH OH O O OH OH O O OH OH OH OH OH O O O OH OH O O OH OH OH Glycogen (& amylopectin of starch) OH O OH etc.

19. GLYCOGEN

20. Carbohydrate – protein/peptide combinations carbohydrate groups can be attached to peptides, polypeptide chains or proteins to form ….. Peptidoglycans – bacterial cell walls – penicillin antibiotics inhibit construction Proteoglycans – Protein + glycosaminoglycans - lubricants in connective tissue cartilage = proteoglycan + collagen Glycoproteins – Proteins with oligosaccharides attached to hydroxyl groups erythropoietin (EPO) – hormone that stimulates RBC production Blood group determinants Even Hemoglobin can be glycosylated – evidence of prolonged hyperglycemia Glycosylation of eye crystallins induce cataracts – connection with diabetes

21. OH Man Man Man GlcNAc GlcNAc Asn OH O OH OH O OH OH HO NH C=O CH3 N-linked core Glycoproteins O – CH2 Ser H O-linked O H || N - C – CH2 - H Asn N-linked

22. Fuc Gal GlcNAc Gal Ser Fuc Gal GlcNAc Gal Ser Fuc Gal GlcNAc Gal Ser GalNAc Gal Blood Types & GlycosylTransferases (EC 2.4) Early stop codon mutation in glycosyltransferase gene results in nonfunctional enzyme A vs. B glycosyltranferase enzymes differ in sequence in only 4/354 residues. H-antigen RBC glycoprotein A B O

23. What is your blood Type? a) A b) B c) O d) AB e) don’t know What is your RH factor? a) + b) - c) don’t know

24. “There are no known natural effects of these differing blood types. People with A, B, AB and O phenotypes do not differ in fitness in any major way that we have been able to detect. This suggests that the complete absence of the enzyme (null mutation) is neutral in the current human population and so is the switch from one form of the enzyme to another. (Suggestions that blood type determines susceptibility to some infections are common in the scientific literature. Most of them have not held up. The best correlation is a possible association between blood type O and susceptibility to cholera. This looks pretty good but the cause-and-effect relationship is still up in the air.) “ Laurence Moran – Professor of Biochemistry – University of Toronto

26. Flu virus’ gain entry into their host cell by binding To (sialic acid) glycoproteins Using the hemagglutinin (H). Did you get a flu shot? a) Yes b) no New viral particles exit by Hydrolyzing the sialic acid off The host glycoprotein using their Neuraminidase (N) Tamiflu is a competitive inhibitor of this process. The H1N1 designation of the flu indicates the type of these two proteins.