BC10-2(part3)

G. Further Elongation of Fatty Acid Chains

1. _______

- 16-carbon

- fully _____ fatty acid

- end-product of fatty acid synthase activity

- can be further elongated and/or desaturated by separate enzymic processes

- enzymes:

- found in the _____ and _____

- can use fatty acids of various chain lengths and degrees of unsaturation as substrates

2. Elongation Systems

- form fatty acids longer than _____-carbons by adding _____-carbon units by _____

a. _____ Systems

- most active

- adds _____ onto palmitate in a manner similar to the action of fatty acid synthase

i. _____ - involved rather than ACP (Acyl carrier protein)

ii. _____

- 18-carbon unit

- common product

b. _____ System

- uses acetyl CoA units rather than malonyl CoA units

- for the synthesis of structural lipids in this organelle

3. _____- additional elongation capabilities  production of very long chain fatty acids (up to _____ carbons) for brain lipid synthesis

H. Desaturation of Fatty Acid Chains

- 2 most common monounsaturated fatty acids in mammals

1. ________ (16 : 1 : 9)

2. ________(18 : 1 : 9)

- ______ double bonds are introduced between carbons 9 and 10 by ______ in the ______ by ______

________

- mixed-function oxidase

- requires

- ________

- ________

- humans lack the ability to introduce double bonds beyond carbons________to ________  ________unsaturated ________and________ acids must be provided in the diet

I. Storage of Fatty Acids as Components of TAG

- fatty acids are esterified through their carboxyl groups  loss of negative charge  formation of neutral fat (if species of acylglycerol is solid at room temperature  “_____”, if _____ “oil”)

1. Structure of TAGs

- triesters of glycerol and 3 fatty acids

- fatty acid on carbon ___ is usually saturated

- fatty acid on carbon ___ is usually unsaturated

- fatty acid on carbon ___ can be either

- presence of unsaturated fatty acid(s)  ___ melting temperature

2. Function

- fatty acids are converted to _____

- for transport between _____

- for storage of ______

- TAGs are only slightly soluble in water  cannot form stable micelles  coalesce within adipocytes  form ___ droplets (major energy reserve of the body) that are nearly anhydrous

a. Fat Deposits

- main stores of metabolic fuel in humans in fat cells (adipocytes)

- very large portion of ingested fats are stored as TAG in the fat droplets of adipocytes  serve long term needs of metabolic fuel

b. Advantages of TAG over Other Forms of Metabolic Fuels

- ___ weight (___ dense than water)

- concentrated form of fuel (complete combustion to CO2 and water  release ___ kcal/g as opposed to ___ kcal/g of carbohydrates and proteins)

- water-insolubility  no ___ problems to the cells

3. Glycerol Phosphate Synthesis

a. _____________

- initial acceptor of fatty acids during the synthesis of TAG

b. 2 Pathways

i. Glycerol _____________

- _____________

- _____________

ii. Glycerol _____________

- _____________ only

- adipocytes can only take up glucose in the presence of _____________(absence of ……….  adipocytes have limited capability to produce _____________  cannot form

_____________)

4. Conversion of Free Fatty Acid to its Activated Form

- fatty acid must be activated to its activated form (attached to ______)  _____________ synthesis

- catalyzed by _____________ ( _____________)

5. Synthesis of a Molecule of TAG from Glycerol Phosphate and Fatty Acyl CoA

a. Acylation of Glycerol

i. 1st Acylation

- 2 routes of acylation of the 1st hydroxyl of glycerol

ia. 1st Route

- uses DHAP (derived from glucose by the glycolytic pathway) as the acceptor of the acyl moiety from the fatty acyl CoA

- initial reaction is followed by reduction (NADPH as the

electron acceptor)  lysophosphatidate

- fatty acid preferentially introduced to form lysophosphatidate is saturated

ib. 2nd Route

- gives the same product

- shows the same preference for a saturated fatty acid

- order is reversed

- reduction of DHAP  glycerol 3-phosphate occurs before

acylation of the C1 hydroxyl

ii. 2nd Acylation

- unsaturated fatty acyl CoA thioester is introduced to the 2-hydroxyl of

lysophosphatidate

- except in the human mammary gland (saturated fatty acyl CoA is used)

iii. 3rd Acylation

- phosphate group on C3 is removed by phosphatase

- followed by addition of either a saturated or unsaturated fatty acid to the C3

hydroxyl

J. Different Fates of TAGs in the Liver and Adipose Tissues

1. Adipose Tissue

- esterification of fatty acids  TAG depends on ongoing carbohydrate metabolism for the

formation of DHAP or glycerol 3-phosphate

- lack glycerol kinase  cannot phosphorylate glycerol to form glycerol 3-phosphate

- only source of glycerol 3-phosphate for TAG synthesis is from DHAP

- entry of glucose into adipocyte is insulin-dependent  insulin is an essential requirement for

TAG synthesis in the adipose tissue

- TAG is stored in the cytosol in a nearly anhydrous form  serves as “depot fat”  ready for

mobilization

2. Liver - little TAG is stored

- most are - exported

- packaged with

- cholesterol

- cholesteryl esters

- phospholipid

- apolipoprotein B-100

 form lipoprotein particles (VLDL)  secreted into the blood  peripheral tissues

MOBILIZATION of STORED FAT (LIPOLYSIS of TAG)

- TAGs provide concentrated stores of metabolic energy (highly reduced and largely anhydrous)

- complete oxidation of fatty acids to CO2 and H2O  9 kcal/g of fat

- proteins and carbohydrates: 4 kcal/g

- alcohol: 7 kcal/g

A. Release of Fatty Acids from TAGs

- initiated by hydrolytic release of fatty acids and glycerol by hormone-sensitive lipase (removes fatty

acids from either carbon 1 or 3 of TAG)

- other lipases specific for MAG or DAG remove the remaining fatty acids

- present in excess

- rate-limiting step of lipolysis in adipocytes

- reaction catalyzed by hormone-sensitive TAG lipase

1. Activation of Hormone-Sensitive Lipase

- activated (by covalent modification) when phosphorylated by a 3’,5’-cAMP-dependent protein

kinasea. Activated cAMP-Mediated Cascade

- fatty acid synthesis is turned off

- TAG degradation is turned on

b. High Insulin and Glucose Levels

 hormone-sensitive lipase dephosphorylation and inactivation

c. Prostaglandins

- inhibit lipolysis by reducing cAMP levels

2. Fate of Glycerol

- adipocytes lack glycerol kinase  cannot metabolize glycerol

- transported through the blood to the liver 

- glycerol phosphate formation  liver TAG synthesis

- conversion to DHAP (reversal of glycerol phosphate dehydrogenase reaction) 

glycolysis or gluconeogenesis

3. Fate of Fatty Acids

- free (unesterified) fatty acids  cross cell membrane of adipocyte  bind to plasma albumin 

fatty acids diffuse to cells  oxidation for energy production

- active transport of fatty acids across membranes mediated by membrane fatty acid

binding protein

- carbon source for lipid biosynthesis

- those that cannot use free fatty acids as fuel

a. Brain - impermeable blood-brain barrier

b. Other nervous tissues

c. RBCs - no mitochondria

d. Adrenal medulla

B. Lipolysis in Other Tissues

- other tissues (muscle, liver) store small amounts of TAG (intracellular lipid droplets) for their own use

- mobilized by the same hormonal controls as are found in adipocytes