Carbohydrates of Physiologic Significance

CARBOHYDRATES ARE ALDEHYDE OR KETONE DERIVATIVES OFPOLYHYDRIC 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 branchedpolymers. 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 proteoglycanfrom cartilage

Structures of A, B,and Ooligosaccharide antigen

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

What are these moleculs ?

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 SIMPLEOR COMPLEX

Fatty Acids Are Named After Corresponding HydrocarbonsSaturated Fatty Acids Contain No Double BondsUnsaturated Fatty Acids Contain One or More Double BondsFatty 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).

A fatty acid (Palmitate 16:0)

Hydrophilic carboxylate head

Hydrophobic hydrocarbon tail

Space Filled Models of FFAs

Common unsaturated fatty acids

w-3 (n-3) unsaturated fatty acids

EPA 20:5 (all cis) D5,8,11,14,17

DHA 22:6 (all cis) D4,7,10,13,16,19

ALA 18:3 (all cis) D9,12,15 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

CH2

O

PO O

O

CH2CHCH2

OO

C O C O

Phosphate

Glycerol

(a) Structural formula (b) Space-filling model

Fatty acids

(c) Phospholipid symbol

Hy

dro

ph

ob

ic t

ail

s

Hydrophilichead

Hydrophobictails

–

Hy

dro

ph

ilic

he

ad CH2 Choline

+N(CH3)3

The Lipid Bilayer

Tails (hydrophobic)

Head (hydrophilic)

Hydrophobic tails

Hydrophilic heads

Hydrophilic heads

bilayer

Lipid Bilayer (Double Membrane)

Hydrophilichead

WATER

WATER

Hydrophobic tail

The phospholipid bilayer is the basic structures of biomembranes

What is this phospholipids name?

a

s

After PI is phosphorylated to PIP2, cleavage via Phospholipase C yields diacylglycerol (and IP3).

O P

O

O

H2C

CH

H2C

OCR1

O O C

O

R2

OH

H

OPO 32

H

H

OPO 32H

OH

H

O

H OH

PIP2 phosphatidylinositol- 4,5-bisphosphate

cleavage by Phospholipase C

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 E1

O

OH OH

CH3

CO2- 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

CH3

CO2-

O

OH

CH3

CO2-

O

Thromboxane A2

Leukotriene A4

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)

CO2-

prostaglandin G2

CO2-O

OOOH

prostaglandin H2

CO2-O

OOH

cyclooxygenase

aspirin,ibuprofin

cyclooxygenase 2 O2

X

stimulus

phospholipase A2lysophospholipid

H2O

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

Perc

en

t

Chylomicron LDLVLDL HDL

100

0

20

40

60

80

Cholesterol

Phospholipid

Protein

Phospholipid

Cholesterol

Triglyceride

VLDL

HDL

LDL

HDL-PON

LDL

OX-LDL

Plaque

Macrophage

Inactiveproducts

Up-regulated by light ethanol

Down-regulated by heavy ethanol

Foam Cell

PON & CAD Status