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Medical Biochemistry Robert F. Waters, PhD

Medical Biochemistry Robert 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.

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Medical Biochemistry Robert F. Waters, PhD

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  1. Medical BiochemistryRobert F. Waters, PhD Lipid Overview

  2. Medical Biochemistry II: Lipids

  3. Fatty Acid Overview:

  4. Fatty Acid Nomenclature • Delta System • Omega System • Saturated vs. Unsaturated • Cis vs. Trans • Carbon Numbering • Alpha carbon, etc.

  5. Fatty Acid Structure

  6. Fatty Acid Structure Cont:

  7. Fatty Acid Composition

  8. 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

  9. 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?

  10. 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

  11. 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)

  12. Peroxidation Continued

  13. 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

  14. 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

  15. 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

  16. Reducing Peroxidation--carotene • Precursor to vitamin A • Free radical scavenger • Quencher of singlet oxygen

  17. Reducing Peroxidation-Iron • Removal of transition metal ions especially Fe++ is important in prevention of hydroxyl radicals (OH)

  18. 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)

  19. Vitamin E • Lipid soluble • Collective term for all the tocopherols and tocotrienols • Difference in double bond location

  20. 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

  21. Vitamin E Biological Function • Protects membranes from oxidative damage (Anti-oxidant)

  22. Not All Vitamin E’s Are The Same • Biopotency based on pharmaceutical or synthetic form of vitamin E called all-rac--tocopheryl acetate

  23. Foods Rich in Vitamin E • Nuts • Seeds • “Margarine” • Vitamin E and unsaturated fatty acids?

  24. 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

  25. 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

  26. Not All Vitamin A’s are the same • Synthetically the -ionone ring has been replaced • Varieties of aromatic rings are added

  27. 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

  28. 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)

  29. Breakdown of Carotenoids

  30. 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

  31. ARAT-acyl CoA:retinol acyltransferase

  32. LRAT-lecithin:retinol acyltransferase

  33. Movement of Retinol Between Tissues

  34. Retinoids and the Retina

  35. 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)

  36. 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

  37. 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

  38. Toxicity and Vitamin A • Toxicity associated with excessive intake • Retinoic acid

  39. Vitamin A Deficiency • Rare in developed countries • Depressed immune function • Night blindness • Xerophthalmia (misshapen cornea) • Drying of conjunctiva and cornea • Xerosis • blindness

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