Carbohydrates of Physiologic Significance CARBOHYDRATES ARE ALDEHYDE OR KETONE DERIVATIVES OF POLYHYDRIC ALCOHOLS (1) Monosaccharides are those carbohydrates that cannot be hydrolyzed into simpler carbohydrates: They may be classified as trioses, tetroses, pentoses, hexoses, or heptoses, depending upon the number of carbon atoms; and as aldoses or ketoses depending upon whether they have an aldehyde or ketone group. Examples are listed in Table 13–1. (2) Disaccharides are condensation products of two monosaccharide units. Examples are maltose and sucrose. (3) Oligosaccharides are condensation products of two to ten monosaccharides; maltotriose* is an example. (4) Polysaccharides are condensation products of more than ten monosaccharide units; examples are the starches and dextrins, which may be linear or branched polymers. Polysaccharides are sometimes classified as hexosans or pentosans, depending upon the identity of the constituent monosaccharides

Anomers

Epimerisation

Important Disaccharides

starch

Glycosaminoglycans (mucopolysaccharides) are complex carbohydrates characterized by their content of amino sugars and uronic acids. When these chains are attached to a protein molecule, the result is a proteoglycan. Proteoglycans provide the ground or packing substance of connective tissues.

Structure of proteoglycan from cartilage

Structures of A, B,and O oligosaccharide antigen

Carbohydrates Can Be Linked to Proteins Through Asparagine (N-Linked) or Through Serine or Threonine (O- Linked) Residues

What are these moleculs ?

Lipids of Physiologic Significance (1) relatively insoluble in water and (2) soluble in nonpolar solvents such as ether and chloroform.

LIPIDS ARE CLASSIFIED AS SIMPLE OR COMPLEX

Fatty Acids Are Named After Corresponding Hydrocarbons Saturated Fatty Acids Contain No Double Bonds Unsaturated Fatty Acids Contain One or More Double Bonds Fatty acids may be further subdivided as follows: (1) Monounsaturated (monoethenoid, monoenoic) acids, containing one double bond. (2) Polyunsaturated (polyethenoid, polyenoic) acids, containing two or more double bonds. ). (3) Eicosanoids: These compounds, derived from eicosa- (20-carbon) polyenoic fatty acids, comprise the prostanoids, leukotrienes (LTs), and lipoxins (LXs). Prostanoids include prostaglandins (PGs), prostacyclins (PGIs), and thromboxanes (TXs ).

The General Structure of Fatty Acids The general structure of a fatty acid is a long hydrocarbon chain with a carboxyl group on carbon 1 (C1). The general structure of a fatty acid is a long hydrocarbon chain with a carboxyl group on carbon 1 (C1).

A fatty acid (Palmitate 16:0) Hydrophilic carboxylate head Hydrophobic hydrocarbon tail

Space Filled Models of FFAs

Common unsaturated fatty acids

 -3 (n-3) unsaturated fatty acids EPA 20:5 (all cis)  5,8,11,14,17 DHA 22:6 (all cis)  4,7,10,13,16,19 ALA 18:3 (all cis)  9,12,15 alpha-linolenic acids

BIOACTIVE LIPIDS: MEMBRANE SPHINGOLIPIDS and GANGLIOSIDES

Triacylglycerides and Phospholipids

Saturated fatty acid ( sn-1 position) Unsaturated fatty acid (sn-2 position) Differences in the length and degree of saturation of fatty acids affect their ability to pack & hence the fluidity of the bilayer Choline head-group Polar Nonpolar Phosphatidylcholine

Phospholipid Structure CH 2 O P O O O CH CH 2 OO C O C O Phosphate Glycerol (a) Structural formula (b) Space-filling model Fatty acids (c) Phospholipid symbol Hydrophobic tails Hydrophilic head Hydrophobic tails – Hydrophilic head CH 2 Choline + N(CH 3 ) 3

The Lipid Bilayer Tails (hydrophobic) Head (hydrophilic) Hydrophobic tails Hydrophilic heads bilayer

Lipid Bilayer (Double Membrane) Hydrophilic head WATER Hydrophobic tail The phospholipid bilayer is the basic structures of biomembranes

What is this phospholipids name? a s

After PI is phosphorylated to PIP 2, cleavage via Phospholipase C yields diacylglycerol (and IP 3 ). Phosphatidyl inositol signal cascades may lead to release of arachidonate.

plasmalogens

Structure of a ceramide (N-acylsphingosine) Structure of sphingomyelin Sphingosine

Four major phospholipids in mammalian cell membranes

(or galactosylceramide)

Structures of common sphingolipids: Gangliosides are just cerebrosides with NANA (sialic acid) attached!

Gangliosides Gangliosides are the most complex sphingolipids. These are carbohydrate-rich sphingolipids that contain at least one acidic sugar. Ganliosides are synthesized by the ordered, step-wise addition of sugar residues to ceramide. Synthesis of these complex lipids requires activated sugars (e.g. UDP-glucose, UDP-galactose, UDP-N-acetylneuraminate…) This is just one example, more than 60 different gangliosides have been characterized. glucose (Glc), galactose (Gal), N-acetylgalactosamine (GalNAc), N-Acetylneuraminate (NAN)

What is these ?

EICOSANOIDS ARE 20-CARBON LIPIDS THAT ACT LOCALLY TO STIMULATE A VARIETY OF PROCESSES Thromboxanes: produced by platelets; act in formation of blood clots & reduction of blood flow at the site of a clot Prostaglandin E 1 O OH CH 3 CO 2 - Prostaglandins: act through cAMP to stimulate contraction of smooth muscle, affect blood flow, elevate body temperature, or cause inflamation & pain Leukotrienes: induce contraction of muscle lining airways to the lungs. I won’t expect you to remember these structures. O CH 3 CO 2 - O OH CH 3 CO 2 - O Thromboxane A 2 Leukotriene A 4

MAMMALIAN CELLS SYNTHESIZE EICOSANOIDS FROM ARACHIDONIC ACID Arachidonic acid is released by breakdown of phospholipids in response to cell damage or hormonal stimuli. phospholipids containing arachidonic acid other eicosanoids arachidonate (20:4) CO 2 - prostaglandin G 2 CO 2 - O O OOH prostaglandin H 2 CO 2 - O O OH cyclooxygenase aspirin, ibuprofin cyclooxygenase 2 O 2 X stimulus phospholipase A 2 lysophospholipid H2OH2O Mammals have two isozymes of cyclooxygenase -- COX-1 & COX-2. The prostaglandins produced by COX-1 participate in “house-keeping” functions such as secretion of gastric mucin; those produced by COX-2 play roles in inflamation. Aspirin, ibuprofin and acetaminophen (nonsteroidal anti-inflamatory drugs, NSAIDS) block prostaglandin synthesis by inhibiting cyclooxygenase.

Figure 5-18 Page 155 Size and Compositions of the Lipoproteins Protein Triglyceride Chylomicron Percent ChylomicronLDLVLDLHDL Cholesterol Phospholipid Protein Phospholipid Cholesterol Triglyceride VLDL HDL LDL

HDL-PON LDL OX-LDL Plaque Macrophage Inactive products Up-regulated by light ethanol Down-regulated by heavy ethanol Foam Cell PON & CAD Status PON & CAD Status