medical biochemistry robert f. waters, phd lipid overview
TRANSCRIPT
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Medical BiochemistryRobert F. Waters, PhD
Lipid Overview
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Medical Biochemistry II: Lipids
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Fatty Acid Overview:
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Fatty Acid Nomenclature
Delta System Omega System Saturated vs. Unsaturated Cis vs. Trans Carbon Numbering Alpha carbon, etc.
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Fatty Acid Structure
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Fatty Acid Structure Cont:
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Fatty Acid Composition
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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
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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?
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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
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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)
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Peroxidation Continued
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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
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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
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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
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Reducing Peroxidation--carotene
Precursor to vitamin A Free radical scavenger Quencher of singlet oxygen
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Reducing Peroxidation-Iron
Removal of transition metal ions especially Fe++ is important in prevention of hydroxyl radicals (OH)
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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)
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Vitamin E
Lipid soluble Collective term for
all the tocopherols and
tocotrienols Difference in double
bond location
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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
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Vitamin E Biological Function
Protects membranes from oxidative damage (Anti-oxidant)
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Not All Vitamin E’s Are The Same
Biopotency based on pharmaceutical or synthetic form of vitamin E called all-rac--tocopheryl acetate
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Foods Rich in Vitamin E
Nuts Seeds “Margarine”
Vitamin E and unsaturated fatty acids?
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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
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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
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Not All Vitamin A’s are the same
Synthetically the -ionone ring has been replaced
Varieties of aromatic rings are added
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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
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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)
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Breakdown of Carotenoids
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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
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ARAT-acyl CoA:retinol acyltransferase
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LRAT-lecithin:retinol acyltransferase
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Movement of Retinol Between Tissues
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Retinoids and the Retina
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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)
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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
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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
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Toxicity and Vitamin A
Toxicity associated with excessive intake Retinoic acid
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Vitamin A Deficiency
Rare in developed countries Depressed immune function Night blindness Xerophthalmia (misshapen cornea) Drying of conjunctiva and cornea
Xerosis blindness