HW #9: 21.36, 21.52, 21.54, 21.56, 21.62, 21.68, 21.70, 21.76, 21.82, 21.88, 21.94, Carbohydrates

Transcription

1 Chemistry 131 Lectures 16 & 17: Carbohydrates Chapter 21 in McMurry, Ballantine, et. al. 7 th edition 05/24/18, 05/25/18 W #9: 21.36, 21.52, 21.54, 21.56, 21.62, 21.68, 21.70, 21.76, 21.82, 21.88, 21.94, Carbohydrates Introduction Carbohydrate is an archaic term. Are sugars really hydrates of carbon? Cn(2)m You could write glucose s molecular formula C6126 as C6(2)6, but the structure really isn t one of a simple hydrate (like MgS472) C 2 Even though sugars are not simple hydrates of carbon, the term helps us interpret their properties: Glucose solubility = 1 gm/ml 2 o Pretty good for an organic molecule of MW = 180 o Syrup! The term saccharide, from L. saccarum, meaning sugar is also used to indicate carbohydrates, typically in relating number of monomeric units (monosaccharide, disaccharide, polysaccharide) 1

2 Biologic uses of carbohydrates: Energy Structure Cellular Recognition Information Storage & Transfer Monosaccharides Structure and Nomenclature Sugars end with ose Families of sugars are indicated by the number of C s Sugars are either aldoses or ketoses o Aldose o Ketose Problem: Below is the Fischer projection for glucose. Classify it in terms of the number of carbons and whether it is an aldehyde or a ketone. For example, D- glyceraldehyde is an aldotriose C C C 2 D-glyceraldehyde C 2 D-glucose 2

3 We will confine our discussion to the following monosaccharides D-glyceraldehyde (D-aldotriose) D-ribose (D-aldopentose) D-glucose (D-aldohexose) D-galactose (D-aldohexose) D-fructose (D-ketohexose) D vs. L Monosaccharides & Fischer Projections C C 2 C C 2 (R)-glyceraldehyde D-glyceraldehyde Question: Is there any difference between (R)-glyceraldehyde and D- glyceraldehyde? Fischer and aworth projections for D-ribose (D-aldopentose) C C 2 3

4 D-glucose (D-aldohexose) C C 2 D-fructose (D-ketohexose) C 2 C 2 D-galactose (D-aldohexose) C C 2 Question: What makes each of the above a D monosaccharide? Answer: Question: Are fructose and glucose isomers of one another? Answer: Question: Are glucose and galactose enantiomers of one another? Answer: 4

5 Amino Sugars C C C N 2 C 2 N 2 C 2 N C 2 glucosamine galactosamine N-acetyl glucosamine The Cyclic Structure of Monosaccharides emiacetals vs acetals cyclic monosaccharides vs. polysaccharides: Glucose: Glucose hemiacetal formation C 2 C 2 Acetal formation between 2 glucose molecues C 2 C 2 C 2 C It is important to recognize which positions are fixed and which can change absolute configuration look for the hemiacetal motif and recall the equilibrium between hemiacetal and aldehydes + alcohol 5

6 The anomeric C: and designation Note that cyclized glucose is a pyranose (6C oxygen containing ring) Conformational representation of glucose (or how to remember the absolute configuration of substituents in cyclized glucose): with the anomeric carbon in the configuration, all of the groups are trans to each other Fructose: Cyclized fructose is a furanose (5C oxygen containing ring) C 2 C 2 Ribose: Cyclized ribose is also a furanose (5C oxygen containing ring) C C 2 6

7 Mutarotation: Pure -D-glucose = +112 o +57 o at equilibrium Pure -D-glucose = o +57 o at equilibrium Question: Which of the 2 conformations do you expect to be more stable? Answer: +57 o corresponds to 64% -D-glucose and 36% -D-glucose; only.003% is in open chain form, but this is enough to make hemiacetals reactive they are reducing sugars The osmotic diuretics mannitol and sorbitol: C C 2 C 2 C 2 C 2 C 2 glucose mannitol sorbitol Notice these are not monosaccharides, they are polyols. Why are they not classified as monosaccharides? Question: Does sorbitol undergo mutarotation? Sorbitol and diabetes: Glucose conversion to sorbitol in the eye by aldose reductase Sorbitol as a sugar substitute for diabetics Take home message - be careful how much sugarless candy you eat! 7

8 Characteristic Reactions of Monosaccharides Glycoside Formation Synonomous with acetal formation; we can lock the cyclic form in place by further reacting a hemiacetal with an alcohol functional group in an acid environment C 2 C 3 + C 2 C C 2 + C 2 C The above is glucose being converted to methyl and -D-glucoside The glycosidic bond is from the anomeric C to the C3 (methoxy) group This is the same type of reaction that occurs when monosaccharides are converted to disaccharides xidation of the Aldehyde Group: Benedict s reagent is Cu +2 complexed with the tricarboxylic acid citrate (of citric acid cycle fame) in alkaline solution: Sugar pen Chain + Cu +2 Blue oxidized Sugar reduced + Cu 2 Rusty Red 8

9 xidation to Uronic Acids: C 2 -UDP 2 NAD + UDPG Dehydrogenase -UDP The enzyme that oxidizes glucose to glucuronic acid recognizes glucose when linked to uridine diphosphate o Interestingly, this is the form used to make glycogen when there is lots of glucose around Glucuronic acid linked to N-acetyl glucosamine forms hyaluronic acid, an important component of connective tissue Glucuronic acid links to non-polar compounds to remove them from the body; an interesting example is the removal of estradiol: Estradiol 9

10 Disaccharides Disaccharide: 2 Monosaccharides linked via a glycosidic bond ligosaccharide: 6-10 monosaccharides linked by glycosidic bonds Polysaccharide: large numbers of monosaccharides linked by glycosidic bonds Maltose: 2 glucose linked via an -1,4-glycosidic linkage Question: Is maltose a reducing sugar? Answer: Sucrose: -D-glucose joined to -D-fructose via an -1,2-glycosidic linkage Question: Is sucrose a reducing sugar? Answer: Lactose: -D-galactose joined to D-glucose via a -1,4-glycosidic linkage Question: Is lactose a reducing sugar? Answer: 10

11 Question: Amylose is a linear polysaccharide that may contain several thousand glucose monomers. Is it a reducing sugar? Answer: Polysaccharides Poly many Saccharum sugar Starch Starch = Amylose + Amylopectin Amylose is unbranched: glucose connected by -1,4-glycosidic linkages 11

12 Amylopectin is a branched polysaccharide: glucose connected by -1,4-glycosidic linkages + -1,6-glycosidic linkages 12

13 Glycogen is also branched via -1,6-glycosidic linkages, only to a greater extent than amylopectin. In the cartoon below, amylopectin is on the left, glycogen on the right Glycogen Glycogen is the major mammalian storage form of glucose. Ca units of glucose (like amylopectin) Ca. 350 g in well nourished individual, split between liver and muscle) Question: ow many glycogen molecules are there in a well-nourished adult? Notice the effect that storage as glycogen has on osmotic balance Question: Given that glucose can only be utilized by taking a glucose off of the end of an -1,4 linked polysaccharide, does it make sense that glycogen is more highly branched than amylopectin? 13

14 Cellulose Cellulose is also unbranched: glucose connected by -1,4-glycosidic linkages Again, structure is driven by hydrogen bonding; only in this case, optimal -bonding leads to tremendous interactions between cellulose polymers 14

15 Cellulose microfibrils orient perpendicular to one another in the formation of the plant cell wall and are cemented with hemicellulose and pectin Pectin is primarily -1,4 linked galactouronic acid and is a principal soluble dietary fiber Average molecular weight of cellulose = 4 x 10 5 or 2,200 glucose units Question: What is the overriding structural feature that governs the physical properties of carbohydrates? 15

16 Acidic Polysaccharides Acidic polysaccharides contain amino sugars, so it is more usual to refer to them as glycosaminoglycans. yaluronic acid Repeating units of glucuronic acid bonded to N-acetyl-glucosamine via a - 1,3-glycosidic linkage, with the N-acetyl-glucosamine bonded to the next glucuronic acid via an -1,4-glycosidic bond o Recall an amino group replaces the hydroxyl at C2 in glucosamine 3 x 10 2 to 1 x 10 5 units, depending on origin The average adult has about 15 g (70 kg individual) about 1/3 of which is turned over daily Adds as a shock absorber/major component in cartilage, wrapping around each chondrocyte. Also a major component of synovial fluid o As an acidic (and thus ionized) polysaccharide what contains highly polar amide groups, water goes ga ga over hyaluronic acid Also abundant in skin, where it is involved in tissue repair Also important in cell adhesion, movement, and proliferation. Correlates well with certain malignancies and as such is used as a tumor marker for certain cancers of the prostate and breast 16

17 Question: Why can individuals take glucosamine as the Cl or sulfate salt when hyaluronic acid is made of N-acetyl-glucosamine? Answer: We have the enzymatic machinery to both make glucosamine-6-phosphate (from fructose-6-phosphate and glutamine) which then is converted to the 1- uridine diphosphate derivative of N-acetyl-glucosamine, much like we saw for activating amino acids for transfer Perhaps we should eat more bugs for the chitin content: N-acetyl-glucosamine with -1,4-glycosidic linkages eparin Variably sulfated polysaccharide chains MW 6,000 to 30,000. Below is shown a much smaller, somewhat more selective version fondaparinux 17

18 Major clinical anticoagulant, also produced and stored by mast cells in the body (which makes sense when you consider the need to recruit cells into areas of inflammation) eparin inhibits many proteins in the blood coagulation cascade eparin should not to be confused with hirudin, a protein which binds directly to thrombin 18