Chapter 12.

Part I. Lipids

Functions of lipids

• Building blocks of membranes• Energy storage• Hormones• Mediators of signal transduction

Lipid classification

• Fatty acids• Triacylglycerols• Glycerophospholipids• Sphingolipids• Steroids• Other lipids

Fatty acidsCarboxylic acids with long-chain hydrocarbon side groups

• Saturated• Unsaturated - double bonds are usually in the cis configuration;

30° bend in the hydrocarbon chain

18:0 18:1 (∆9) 18:2 (∆9,12) 18:3 (∆9,12,15)

ω-3 fatty acidω-6 fatty acid

ω1

2

34

56

1ω

23

Structural features of storage and membrane lipids

Triacylglycerols (Triglycerides)• Triesters of glycerol and fatty acids• Fats or oils• Energy storage and thermal insulation

Trans fats

Strong contributing factor of coronary heart disease

(↑LDL, ↓HDL)

Major food sources for trans fat for American adults

FDA “Trans Fatty Acids in Nutrition Labeling, Nutrient Content Claims, and Health Claims” (July 11, 2003)

Adipocytes (Fat cells)• Synthesis and storage of fats• Secretion of protein hormones in related to the glucose

homeostasis (adiponectin, leptin, resistin etc)

Glycerophospholipids

• Amphiphilic• Major lipid

components of biological membranes

• Signal transduction

tail

head

Phospholipids are hydrolyzed by phospholipases

Sphingolipids

Sphingosine

• Glycolipids• Abundant in brain and nerve membranes• Cell-cell recognition

Steroids

CholesterolSteroid core structure

Cholesteryl esters

Functions of steroids

• Component of membranes– cholesterol

• Bile acids (helping digestion of dietary fats)– Cholic acid and glycocholic acid

• Hormones– estrogens– androgens– progestins– glucocorticoids– mineralocorticoids

Cholesterol

• Membrane component• Precursor of steroid

hormones• Precursor of bile salts

Steroid hormones

Bile acids

Phytosterols

Vitamin D

Inactive

Enzymatic hydroxylation

This active form promotes the intestinal absorption of dietary Ca2+, thereby increases serum [Ca2+] and subsequently the deposition of Ca2+ in bones and teeth

Other fat-soluble vitamins

(Photoreceptor in the eye)(Electron transfer in mitochondria)

(Blood clotting)

(Antioxidant of membrane proteins and lipids)

Isoprenoids (=terpenoids)

(citrus fruits) (vitamin A precursor)

(plant hormone)

(precursor of plant and animal steroids)

(antioxidant)

Eicosanoids

• Derived from arachidonic acid (C20)• Prostaglandins, thromboxanes and

Leukotrienes• Regulate pain, fever, blood pressure,

blood coagulation, and reproduction• Produced and act locally at low

concentrations (10-12 to 10-14M)• Short lifetimes (seconds to minutes)

(Cyclooxygenase, COX)

Arachidonate pathway

COX Enzymes

• COX-1– Constitutive, expressed in most tissues– Cell maintenance and housekeeping– Synthesis of prostaglandins responsible for

protection of the stomach lining• COX-2

– Induced by inflammatory stimuli such as injury or disease

– Synthesis of prostaglandins responsible for pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAIDs)

Selective inhibitor of Cox-2

Inhibitors of Cox-1 and Cox-2

(Tylenol)

(Advil, Motrin)

Little anti-inflammatory effect