LIPID 2014 for PBCM
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LIPID 2014 for PBCM

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notes for my students.

notes for my students.

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LIPID 2014 for PBCM LIPID 2014 for PBCM Presentation Transcript

  • At the end of the class, you should be able to: 1. State the classes of lipid 2. Explain what is saponification  LAB 3. Explain fatty acid degradation in ß-oxidation 4. Explain fatty acid biosynthesis using Palmitate as an example LIPID
  • Lipid classes May be classified in many different ways Can be subdivided into : 1. Fatty acids & their derivatives 2. Triacylglycerol (TAGs) 3. Wax esters 4. Phospholipids 5. Sphingolipids 6. Isoprenoids
  • Some naturally occurring fatty acids: SFA (saturated fatty acids): - 4:0 Butyric acid - Milk fat - 12:0 Lauric acid - coconut oil - 14:0 Myristic acid - Coconut oil, palm nut oil, most animal and plant fats - 16:0 Palmitic acid - Animal and plant fats - 18:0 Stearic acid - Mostly animal fats and some plant fats - 20:0 Arachidic acid - Peanut oil MUFA (monounsaturated fatty acids): - 16:1 Palmitoleic acid - Marine oils, small amount in animal and plant oils - 18:1 Oleic acid - palm oil and animal fats PUFA (polyunsaturated fatty acids): - 18:2 Linoleic acid - Corn, safflower, soybean, cottonseed, sunflower seed and peanut oil - 18:3 Linolenic acid - Linseed (flax), soybean and other seed oils - 20:4 Arachidonic acid - Animal fats Essential fatty acids (EFA): - Linoleic acid (18:2) and linolenic acid (18:3) are essential fatty acids (human body cannot synthesize these fatty acids due to lack of desaturase enzymes)17
  • What is it?
  • In saponification, 1. a water molecule is removed from a fatty acid or an ester. 2. sodium stearate, sodium oleate or sodium palmitate is formed. 3. it is precipitated from the solution by addition of NaCl. 4. the addition makes the sodium salt of fatty acid partially insoluble in water. 5. the product then separates out of the solution 6. the remaining solution has glycerol and sodium chloride. function? http://educationalelectronicsusa.com/c/org_mat-V.htm
  • anabolism catabolism metabolism
  • Lipid metabolism serum glucose Insulin promotes TAGs synthesis =lipogenesis Insulin facilitates transport of glucose to adipocytes Adipocytes cannot synthesize TAGs when glucose levels are low E levels Body’s fat stores are mobilized = lipolysis Several hormones stimulate hydrolysis of TAGs in adipose tissue  glycerol & fatty acid
  • Introducing the intermediate in lipid metabolism…
  • Q: How do we generate energy from fatty acid?
  • 3primary resources of fatty acids for energy metabolism 1. Dietary triacylglycerols 2. Triacylglycerols synthesized in the liver 3. Triacylglycerols stored in adipocytes as lipid droplets
  • What? Where? Why? How? http://www.rose-hulman.edu/~brandt/Chem331/Lipid_Breakdown.pdf Fatty acids degradation
  • • Fn to generate E • Occur in mitochondria and peroxisomes • Remove 2C from carboxyl end of fatty acids ß-oxidation • To degrade odd-chain or branched chain molecules  α-oxidation Fatty acids degradation
  • Triacylglycerols are combined with dietary cholesterol and proteins to form LIPOPROTEIN Lipase catalyses hydrolysis of ester linkages in fats Fatty acids are taken up into the intestinal mucosa They are resynthesized into triacylglycerols
  • • Triacylglycerol are transported by chylomicrons • Chylomicrons are one of the plasma lipoproteins • released by exocytosis from enterocytes into lacteals, lymphatic vessels originating in the villi of the small intestine • during the circulation, chylomicron accept apolipoprotein C-II from HD Lipoproteins. •APOC2 is a cofactor for lipoprotein lipase activity • Fatty acids that have been delivered to muscle tissue via blood capillaries diffuse through cell plasma membrane into the cytoplasm • From cytoplasm/cytosol it will undergo degradation in the matrix mitochondria. • HOW?
  • Chylomicrons
  • Lipid metabolism 1. Fatty acids must get into mitochondrial matrix to be degraded. How to get in ? Fatty acid Fatty acyl CoA ATP AMP +PPi CoASH • f.a. are activated to form fatty acyl CoA by acyl-CoA synthetase • CoA is the acyl carrier • Fatty acyl CoA can enter into intermembrane space
  • 2. Fatty acyl-CoA degradation occur inside mitochondrial matrix & can’t across the inner membrane. How to get into the matrix ? By using a carrier = carnitine Acylcarnithine carnitine CoASH Carnitine acyltransferase I Enter matrix Transport by a carrier protein Acyl-CoA Fatty acid degradation
  • 3. Now Acylcarnithine has enter the matrix. How to form back into fatty acyl-CoA ? Acylcarnithine carnithine CoASH Acyl-CoA Intermembrane space Transport back by carrier protein Fatty acid degradation
  • Fatty acid degradation
  • β-oxidation Occur in 4 steps 1. Oxidation/Dehydrogenation = removal of electrons 2. Hydration = add water 3. Oxidation = remove more electrons 4. Thiolysis (Carbon-Carbon bond cleavage) = remove acetyl-CoA 4. What happen to fatty acyl-CoA ? How to degrade acyl CoA and generate E? Fatty acid degradation Animation: http://www.uwsp.edu/chemistry/tzamis/boxanim.gif http://medstat.med.utah.edu/kw/biochem_animations/betaox.html
  • 1. Oxidation : -electrons, -2H Forms double bond 2.Hydration Form –OH 3. Oxidation : - more electrons, - 2H Forms C=O 4. Thiolysis :+ CoASH & cleave to -acetyl-CoA Fatty acid degradation
  • After ß-oxidation of one cycle: 1. One FADH2 2. One NADH 3. One acyl-CoA 4. One acetyl –CoA To determine total ATP, you must know number of ß-oxidation cycle. Fatty acid degradation
  • • Most of acetyl CoA is used by TCA cycle or isoprenoid synthesis • But some acetyl CoA follow alternate pathway: •During fasting/starvation  glycolysis ↓ [OAA become depleted and could not accept acetyl-CoA] and gluconeogenesis ↑ •Therefore the excess of acetyl CoA  is converted to ketone bodies by ketogenesis (occur in matrix of liver mitochondria) •Ketone bodies = acetoacetate, ß-hydroxybutarate, acetone •They are water soluble lipids and can be readily transported in the blood plasma • Ketone bodies can be used to generate E (as a substitute to glucose) in brain, cardiac & skeletal muscle
  • Question: What happen if our diet contain: Low in fat? High carbohydrate ?
  • FATTY ACID BIOSYNTHESIS • Occur in cytoplasm / chloroplast (plants) •In adults = mainly liver cells and adipocytes, some in mammary gland during lactation • Synthesize when diet is low in fat and/or high in carbohydrate. • Most are synthesized from glucose: • Glucose  Pyr transport to mitochondrion  acetyl –CoA  citrate  citric acid cycle OR into the cytoplasm to make fatty acids • fatty acids are synthesized by the repetitive addition of two- carbon to the growing end of hydrocarbon chain. Fatty acids biosynthesis Acetyl-CoA can be formed by ß-oxidation or decarboxylation of pyruvate Animation:http://www.uwsp.edu/chemistry/tzamis/fasynthanim2003.gif
  • • The usual product of fatty acid anabolism is Palmitate (16C, saturated) • during two carbon-elongation, malonyl-ACP is used • Malonyl ACP is the main substrate •There are 6 steps in one cycle of synthesis. • involves ACP as the acyl carrier protein 1. Priming the system by acetyl-CoA 2. ACP-malonyltransferase reaction 3. Condensation 4. First reduction 5. Dehydration 6. Second reduction
  • Fatty acids biosynthesis e.g. palmitate 1. Priming One acetyl-CoA is required for each molecule of palmitate produced 2. ACP-malonyltransferase reaction Malonyl is transfer to the system 3. Condensation Formation of acetoacetyl-ACP CO2 is released 4. First reduction Use NADPH as reducing agent 5. Dehydration Water is removed 6. Second reduction Use NADPH as reducing agent Cycle repeats 6 more time to produce 16C palmitate
  • Do this: Study the differences between ß-oxidation and fatty acid synthesis.
  • Lipid classes 1. Fatty acids • monocarboxylic acids that occur in Triacylglycerol, phospholipids & sphingolipids • saturated @ unsaturated 2. Triacylglycerols • are esters of glycerol with 3 fatty acids. • if solid at room temp.  fat (mostly saturated f.a) • if liquid at room temp  oil (mostly unsaturated f.a) • major storage & transport form of f.a • important E storage (8x glycogen) • less oxidized than carbohydrate  its oxidation releases more E
  • Nonpolar hydrophobic tail CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 C O O “Polar” hydrophilic head Fatty acid :12-20 C Triacylglycerol @ triglyceride Before a fat can be oxidized, it must be hydrolyzed to the anion acid and glycerol. Biologically this is done by lipases. Chemically base hydrolysis is called saponification. Lipid classes H
  • Lipid classes saponification CH2 CH CH2 O O O C O C O C O R3 R3 R3 3 KOH CH2 CH CH2 OH OH OH + KO C O R3 K salt of a fatty acid 3 2
  • Lipid classes 3. Phospholipids • structural components of membrane • 2 types : phosphoglycerides & sphingomyelins 4. Sphingolipids • Important comp. of animal & plant membranes • Contain long chain amino alcohol: sphingosine (animal) & phytosphingosine (plants) 5. Isoprenoids Molecule containing repeating 5C isoprene Consist of terpenes & steroids 6. Wax esters Complex mixtures of non polar lipids Serve as protecting coat