Medical BiochemistryRobert F. Waters, PhD

Lipid Overview

Medical Biochemistry II: Lipids

Fatty Acid Overview:

Fatty Acid Nomenclature

Delta System Omega System Saturated vs. Unsaturated Cis vs. Trans Carbon Numbering Alpha carbon, etc.

Fatty Acid Structure

Fatty Acid Structure Cont:

Fatty Acid Composition

Fatty Acids and “Good and Bad Cholesterol”

Saturated FA Raise Good and Bad Cholesterol

Monounsaturated FA Raise HDLs and Lower LDLs

Polyunsaturated FA Maintain HDLs and Lower LDLs

Trans fatty acids Lower HDLs and Raise LDLs

Essential Fatty Acids Linoleate (GLA) Linolenate Arachidonic Acid is essential and may be

formed from dietary linoleic acid Note: Essential FAs are because we do not

have enzymes to produce double bonds beyond carbon 9

Conjugated FA in “Organic Beef” Cancer treatment?

Fat Storage Control Mechanism

Leptin System (Not well known yet) Small molecular weight protein produced by

white adipose tissue Has numerous metabolic effects where one is

in the hypothalamus---- Leptin with its receptor molecule suppresses food

consumption by increasing the release of corticotropin-releasing hormone and suppression of something called a neuropeptide Y

Lipid Peroxidation

Inhalation of high concentration of oxygen causes excessive peroxidation of unsaturated FAs

Polyunsaturated FA susceptible to spontaneous peroxidation (non-enzymatic)

Autocatalytic Due to presence of oxygen and some metal ions

like Fe++ Daisy chain effect Causes membrane damage and allows for greater

cytotoxicity (less selective permeability)

Peroxidation Continued

Reducing Peroxidation

Antioxidants (Reduce oxidative damage) Vitamin E (-tocopherol)

Functionally related to the status of— Selenium Vitamin C Iron -carotene Sulfur containing amino acids Overall anti-oxidant defense

Reducing Peroxidation-Selenium

The more the selenium, the less vitamin E is necessary

Selenium associated with glutathione peroxidase which is involved in free radical reduction

Reducing Peroxidation-Vitamin C

Water soluble free radical scavenger and reducing agent

Complements vitamin E function Involved in the formation (rejuvenation) of

reduced vitamin E

Reducing Peroxidation--carotene

Precursor to vitamin A Free radical scavenger Quencher of singlet oxygen

Reducing Peroxidation-Iron

Removal of transition metal ions especially Fe++ is important in prevention of hydroxyl radicals (OH)

Reducing Peroxidation-Sulfur Containing Amino Acids

Muscular dystrophy occurred in animal studies when fed a Vitamin E deficient diet along with lacking selenium and sulfur containing amino acids

Sulfur containing amino acids is necessary for the synthesis of reduced GSH N-acetylcysteine Methionine (SAMe)

Vitamin E

Lipid soluble Collective term for

all the tocopherols and

tocotrienols Difference in double

bond location

Vitamin E Absorption/Transport

Lumen of intestine Tocopherol ester hydrolyzed to free tocopherol by

pancreatic lipases Packaged in chylomicrons Stored in liver and packaged in VLDLs Transported to peripheral cells Bound to a protein to facilitate transfer between

membranes -tocopherol transfer protein

Vitamin E Biological Function

Protects membranes from oxidative damage (Anti-oxidant)

Not All Vitamin E’s Are The Same

Biopotency based on pharmaceutical or synthetic form of vitamin E called all-rac--tocopheryl acetate

Foods Rich in Vitamin E

Nuts Seeds “Margarine”

Vitamin E and unsaturated fatty acids?

Vitamin A and Carotenoids

Fat soluble vitamin Exhibit biological activity of retinol

Alcoholic form of Vitamin A Over 530 carotenoids found in nature with

less than 50 have Vitamin A activity NOTE: The term “retinoids” describe

retinol like compounds NOT necessarily biological activity

Structure of “Retinoids”

Three basic structural components -ionone ring Polyunsaturated chain Polar end group

Vitamin A is stored as retinyl esters Retinol esterified with long chain fatty acid Loss of polar end group

Not All Vitamin A’s are the same

Synthetically the -ionone ring has been replaced

Varieties of aromatic rings are added

Vitamin A Absorption and Metabolism

Absorption of retinyl esters Hydrolysis by retinyl ester hydrolase by a

pancreatic and brush border membrane form of the enzyme

All trans form is preferred

Carotenoids

Absorbed at lower efficiency than retinol May be broken down immediately Or, stored in liver and adipose tissue

False child jaundice Oxygen scavenger (Anti-oxidant itself)

Breakdown of Carotenoids

Storage and Mobilization of Vit.A

Stored as retinyl esters Esterification with long chain fatty acids that

make retinol very hydrophobic and therefore accumulates into droplets

Esterification enzymes ARAT-acyl CoA:retinol acyltransferase LRAT-lecithin:retinol acyltransferase

Both ARAT and LRAT are membrane integrated enzymatic proteins

ARAT-acyl CoA:retinol acyltransferase

LRAT-lecithin:retinol acyltransferase

Movement of Retinol Between Tissues

Retinoids and the Retina

Synthesis of Retinal & Retinoic Acid

Retinol may be converted to retinal Dehydrogenation of retinol with electron acceptors

NAD+ and NADP+ Retinoic acid is produced from further oxidation

from retinal Converted into other metabolites Not known true nature of retinoic acid Involved in genetic control Oxidation may be involved with Cytochrome P450

(Microsomal)

Retinol Binding Proteins

RBP-retinol binding protein Synthesized in liver Mainly a carrier of retinol in plasma

RBP is bound to TTR (transthyretin) TTR is a carrier of thyroid hormones in blood Binding of RBP to TTR prevents plasma loss

of small molecular weight RBP by glomeruli filtration

Food Sources of Vitamin A

Preformed retinol Liver Whole and fortified milk Eggs

Carotenoids Yellow-orange vegetables and fruits

Carrots, sweet potato

Dark-green leafy vegetables Spinach, broccoli

Toxicity and Vitamin A

Toxicity associated with excessive intake Retinoic acid

Vitamin A Deficiency

Rare in developed countries Depressed immune function Night blindness Xerophthalmia (misshapen cornea) Drying of conjunctiva and cornea

Xerosis blindness