Microreview. A.-F. Miller, 2008, pg

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1 Microreview Polysaccharides: a vast diversity based on stereochemistry. Stereochemical differences are associated with secondary and tertiary structural differences: nature s huge and plentiful polymers. Chemical varieties also exist: oxidation and reduction, sulfates, phosphates, amines, N-acetyls. Chemical differences are associated with functional differences. Signalling, recognition. Mixed copolymers with proteins: peptidoglycan cell walls, glycoproteins. Extending protein life times and modulating their interactions with water. 1

2 Comparison of cotton to synthetics. polypropylene 2

3 3 glycation vs. glycosylation Glycosylation is enzymatic addition of polysaccharides of specific sorts to specific sites on proteins. eg. N-glycosylation with 2 NAcGlucosamine followed by high mannose or other, at -N-x-S- or -N-X-T- or -N-X-C- (X P). Common in eukaryotes and archea. Glycation is the non-specific non-enzymatic addition of sugars to proteins or lipids. Accumulates with age because glycated proteins are eliminated at 1/3 the rate of non-glycated proteins. Accumulates more when high blood sugar levels are high (diabetes). A chemical basis for development of flavor and colour in the course of cooking foods.

4 In food: Maillard reactions and Amadori rearrangements Maillard reactions begin with reaction between reducing end of a sugar and an amine group (from protein), yielding a glycosylamine. HNR HC O HC OH CHOH CHOH + H 2 NR CHOH CHOH 4

5 Amadori rearrangement HC O -H 2 O Schiff base NR HC Amadori product HNR HCH CHOH + H 2 NR CHOH C O CHOH CHOH CHOH Advanced Glycation End-products (AGEs) Transition metal ions 5

6 Glycation in cooking When reducing sugars are heated with protein or fats, and an intermediate amount of water. Products produce desirable flavour and colour, but also acrylamide and other carcinogens, including AGEs. Proteins with high Lys content such as those in milk. 6

7 Glycation in vivo Reducing sugars: glucose. Fructose and galactose are ten times more active in this regard (but less prevalent in blood). Slow advancement to AGEs, which can be reactive and stimulate symptoms of type II diabetes mellitus, cardiovascular disease and atherosclerosis (endothelial cells), Alzheimer s disease (protein plaques), cancer, peripheral neuropathy, deafness (damage to myelin). Diabetic high blood sugar results in accumulation of glycated hemoglobin. Long-lived cells are most prone to AGE accumulation: nerve and brain cells, as are long-lived proteins: crystallin in eyes and collagen, and DNA. 7

8 Lipids Hydrocarbon chains: both H and C in their most reduced form: with the highest potential for oxidation and thus energy release. 38 kj/g vs. 17 kj/g protein or CHO. Hydrocarbon is non-polar so it is not soluble in water on its own, and forms separate phases. Hence various couplings to polar head groups, and spontaneous formation of membranes, micelles. Lipids are generally thought of as linear, but non-linear hydrocarbon molecules that are also very non-polar and predominantly associated with fats are also considered. 8

9 Fats, terpenes, steroids Fatty acids: HC chain with carboxylic acid head. Named according to chain length and double bonds. Stearic acid = octadecanoic acid = 18:0 Double bonds decrease the density of H atoms and thus the stiffness of the chain. However double bonds have restricted local rotation. They are commonly cis. The bends impede tight parallel packing of chains and produce more fluid membranes. (Bacteria produce some branched and cyclic fatty acids that alter membrane packing.) 9

10 Health and unsaturation Unsaturated fatty acids are more common in nature: oleic acid, 18:1(9) has one double bond following C9. More than 4 double bonds is rare. Bacteria generally have only one. We must ingest either linoleic acid (LA) or α-linolenic acid (ALA) (plant sources). Linoleic is a precursor for biosynthesis of arachidonic acid and down-stream prostaglandins (inflamation response etc.) Too high a linoleic:linolenic ratio has been implicated in chronic low-level inflamation. 10

11 Saturated vs. not Unsaturated fatty acids, esp. polyunsaturated are associated with lowered risk of cardiovascular disease. Animal fats, palm and coconut oils are highly saturated Corn oil: high in linoleic A. (but low linolenic). Margarine: better than butter re. unsaturation BUT contains trans fats. 11 G&G Fig. 8.1

12 dietary unsaturated fatty acids All mono-unsaturated fatty acids are not equal. EPA and DHA are needed for neural tissue, brain is some 8% EPA and DHA by mass. These are ω-3 fatty acid derivatives. ω-6 fatty acids can be synthesized from LA (linoleic acid) ω-3 fatty acids can be synthesized from ALA (α linolenic acid) Modern American diet is 10:1 ω-6 : ω-3. A better balance would be 4:1-2:1. pp

13 ω-6 fatty acids are precursors of arachadonic acids and then prostoglandins. These are excitatory signals and support chronic a low-level pro-inflammatory condition, elevated blood pressure, among others. Unremitting stress is blamed for degenerative conditions assocaited with our lifestyle. 13

14 Triacyl glycerols / triglycerides Esterification of fatty acid with alcohol results in a neutral product (no more acid functionality). The 3-C alcohol glycerol is the most common one, and links three fatty acids. Mainly deposited in adipose: major energy reservoir. 14 G&G Fig. 8.3

15 diacyl and monoacyl glycerols More polar, can be suspended in water as part of small organized structures: micelles. Phosphate group on third C: glycerophospholipids Phosphate can like the diacylglycerol to additional functionalities: ethanolamine, serine, choline, inositol. Chemically monolithic side chains but diverse head groups (associated with roles in signalling). 15

16 Various head-groups characterize glycerophospholipids. 16 G&G Fig. 8.6

17 Monoacyl glycerides Even more water-soluble: detergents. Result from removal of one fatty acid chain from diacyl glycerides. Can dissolve cell membranes: amplify the significance of the phospholipase in snake venom. 17

18 ether and amide linked lipids Tissue and organ specificity, recognition, signalling, immunity are related to even small quantities of glycosphingolipids. 18 Fig 8.8, 8.11

19 Gangliosides contain N-acetylneuraminic acid 19 Fig 8.14 Note that now the polar head group is comparable in size to the non-polar lipid chains.