Week 4 Lipids Flashcards
Saturated FA Structure
- Methyl start (w/n) and carboxyl end (alpha)
> Stearic acid (C18:0)
> Oleic Acid (C18:1, w-9)
> Linoleic Acid (C18:2, W-6; unsaturated at two positions with DB) - Glycerol + 3 FA –> B oxidation (lipogenesis/lysis via lipase) –> TG + 3 H2O with ester bonds
FA Synthesis (Cytosol)
- Acetyl CoA –> Malonyl CoA (Rate-limiting) –> Palmitate (C16:0) –(elongases/desaturases) –> linoleic acid (C18:2)
> Human desaturates only work upto a-9 (no W-3/W-6 made, so they are essential) - Proteins involved: ACP (Acyl-carrier), NADPH, ACC and FAS
> Food intake –> insulin –> ACC on –> fat production
> Fasting –> AMPK/TRB3 –> ACC off –> fat utilization
FA Degradation
Carnitine transports FA into mitochondria –> 2C stripped at a time via B-oxidation –> Ac-CoA –> TCA cycle
Essential FA: Alpha-Linolenic Acid (C18:3; W-3)
Alpha-linolenic (AHA) –> Eicosapentaenoic Acid (EPA) –> Docosahexaenoic Acid (DHA, C22:6, W-3)
> EPA: signals in thromboxane and prostaglandins (C20:5, W-3): decrease blood clotting and inflammation; W-6 increase both upon cyclooxygenase + lipooxygenase binding)
> DHA: 60% rods/retina (eye) and 20-25% brain; protects heart/lower arrhythmia risks; lower dementia risk by 50% (low blood DHA –> more brain impairment)
Essential FA: Linoleic Acid (C18:2; W-6)
Linoleic Acid –> Arachidonic Acid (C20:4, w-6) –>
1. Thromboxane (COX-1; vasoconstriction, platelet aggregation)
2. Prostaglandins (COX-1 and COX-2; gastric protection, pain and inflammation)
> Aspirin: COX off
Lipid Digestion (SI): Overview
- Difficult to hydrolyze due to long FAC being water insoluble
- 95% reabsorbed (Good energy source)
- Lecithin (phospholipids): DG (glycerol + 2 FA on top 2 C’s, phosphate and choline)
Lipid Digestion Regulation
Large fat enter SI –> cholecystokinin (CCK) –> bild acids/lecithin (Gallbladder): smaller particles –> lipase (pancreas): FA + MG –> reabsorbed in villi via micelles –> TG reform and combine with cholesterol, proteins and phospholipids –> chylomicrons
Lipoprotein: Overview
Components: TG + cholesteryl esters, phospholipids, cholesterol and membrane protein
Lipoprotein: Cholesterol
- Cell membrane; estrogen, testosterone, vitamin D, bile acid precursor
- Produced by liver (20%) and rest of body (80%) ANIMALS only
> Non-essential: body compensates for overproduction of blood cholesterol
> Diabetic: 1 egg/day –> increase risk of death 2x
Lipoprotein: Chylomicrons, VLDL, LDL, HDL Trends
- Decreasing triacylglycerol amount and Increasing protein content
- Chylomicrons + VLDL have the most TG; LDL most cholesterol (45%)
- Chylomicrons (lipase in body cells breakdown; remnants to liver as VLDL) –> VLDL (breakdown in tissues; back to liver; become LDL) –> LDL (taken up by receptor pathways; back to liver; become HDL) –> HDL (came from liver and intestines that bud off lipoproteins and transport cholesterols for disposal)
Lipoprotein: Chylomicrons
Transport lipids and cholesterols from SI –> liver and tissues
> When lipoprotein lipase in blood vessels release FA –> muscles burn them and adipose store them
Lipoprotein: VLDL
Lots of lipids; major supplier of liver FA to tissues
> When lipids removed –> density increases –> LDL and VLDL remnants
Lipoprotein: LDL
VLDL –> LDL as lipids are removed from blood (usually LDLR are in charge, supported by low saturated fat; protects brain function from stroke/dementia)
> Atherosclerosis: blood LDL accumulates –> oxidized from inflammation (CVD biomarker) –> WBC scavengers remove LDL –> artery plaques (trans fat, smoking, HTN)
> Early: foam cells from macrophage and smooth muscle cell uptake, WB Immune cells, artery injury
> Late: plaques and foam cells
> Dementia: thromboembolic occlusion of arteries and infarction and failure to remove Ab from brain
Lipoprotein: HDL
Scavenge cholesterol –> return to liver
CVD and Blood Cholesterol Level (TC)
- High TC/oxidized LDL –> higher chance of CVD
- Treatment:
> LDL receptor to un-mutate (heterozygotes in adulthood especially)
> PCSK9 (Degrade LDLR): must inactivate to reduce LDL (Evolocumab, alirocumab) - Statins: inhibit HMG-CoA reductase –> no cholesterol –> lower LDL and inflammation; damages mito (muscle pain, memory loss, diabetes, 2x breast CA)
- Baby Aspirins:
> Reduce blood clotting and inflammations; GI tract damage (10% ulcers) - Controversial: replace trans and saturated fat with mono- and poly-unsaturated fat
Fat Tissues: Types
- White: Storage (Large fat droplet + small nucleus surrounded in membrane)
- Brown: mitochondria-rich; thermogenesis (energy dissipation)
> Irisin (exercise induced): converts white to brown
Adipose Tissue Turnover and Hormonal Control of Lipase
- Lipolysis: mobilization of stored fat in adipose tissue (cytokine- and hormone-regulated)
> Insulin promotes storage; glucagon/stress promotes mobilization (conversion between FA + glycerol to TG) - Hormone control:
> Preprandial/between meals –> glucagon –> HSL –> FA release –> catabolic energy
> Feeding –> Insulin –> no HSL –> less FA release –> less energy (anabolic)
Adipose signals affecting diabetes
- Hyperglycemic: resistin, TNF-a, IL-6, cytokines, RBP4
2. Hypoglycemic: leptin, adiponectin, visfatin, omentin
Types of Body Fat
- Subcutaneous: insulation (80%)
- Visceral: around organs
> Upper body mostly; insulin resistance (Type II, CVD, HTN) - Harmful: oxidation:
> Rancid oils: PUFA most vulnerable; oxidized
> Causes: UV exposure (PUFA should be kept in dark; Vitamin E counters)
> Cis (bent backbone) Oleic Acid –(partial hydrogenation)–> Increased trans form Elaidic Acid –> MI risks increase (FDA wants to remove artificial trans fat)
