BIOC 503 - Fatty Acids B-Oxidation

70

About ___ % of energy/ATP comes from lipids B-oxidation compared to glucose metabolism

sources of B-oxidation substrate

• dietary fats aka from chylomicrons

• adipose tissues

• lipoproteins

digestion of TAGS

1. bile salts emulsify dietary fats in small intestine forming micelles

2. intestinal lipases from pancreas degrade TAGs

3. Free fatty acids taken up by intestinal mucosa and converted back to TAGs

4. TAGs transported by lipoprotein chylomicrons

5. lipoprotein lipases activated by ApoC-II hydrolyze TAGs

6. Free fatty acids enter tissues

7. Muscles oxidize them for fuel/adipose tissue reesterify them for storage

insoluble, complex

___, ___ lipids are transported in the blood as components of lipoproteins

lipoprotein lipase

TAGs in lipoproteins are hydrolyzed to fatty acids by the enzyme ____ which is activated by ApoC-II sitting on surface of chylomicrons

hormone sensitive lipase

When hungry, fatty acids a released from stored TAGs by ____ enzyme in adipose tissue

glucagon, epinephrine

___ & ___ both activates adenylyl cyclase, increasing cAMP levels, activating PKA enzyme which phosphorylate and activate hormone sensitive lipase

activates, deactivates

glucagon and epinephrine ___ hormone sensitive lipase

insulin ___ hormone sensitive lipase

activated

Before fatty acids can be oxidized for energy/fuel, they need to be ___ aka they need to be attached to a CoA molecule

Fatty acyl-CoA

name of molecule of ACTIVATED fatty acids

1. Fatty acid added to a phosphate group from ATP by ___ enzyme

2. CoA is added to fatty acid with the phosphate group as leaving group (aka release AMP and fatty acyl-COA) by ___ enzyme

* pyrophosphate is a byproduct of this activation cycle and get broken down by inorganic phosphatase and make the reaction highly exergonic

** 2 steps, SAME enzyme

reaction formula for activation of fatty acids

fatty acid + CoA + ATP = fatty acyl-CoA + AMP + 2Pi

Fatty acyl-CoA synthetase

• requires 2 ATP because it converted ATP to AMP, 2 bonds were hydrolyzed, so it is the EQUIVALENT of 2 ATP

synthetase

when an enzyme is named ___ is means that requires ATP to function

cytosol

activation of fatty acids to make fatty acyl-CoA happens in the ___

carnitine shuttle

The ___ carries LONG chain fatty acids across the mitochondrial inner membrane which is impermeable to fatty acyl-CoA

mitochondrial matrix

fatty acid B-oxidation happens in the ___

carnitine acyltransferase 1

___ (CAT1) carnitine shuttle enzyme adding carnitine to fatty acyl-CoA so that it can go through transporter

transporter

carnitine ___ is the part of the carnitine shuttle that make carnitine-fatty acyl cross the inner mitochondrial membrane

carnitine acyltransferase 2

___ (CAT2) reform fatty acyl-CoA by separating carnitine and fatty acyl and adding CoA back

• carnitine goes back through the transporter

B-oxidation

1. acyl-CoA dehydrogenase creates double bond between alpha and beta carbons near CoA end of fatty acyl-CoA & produce FADH2

2. enoyl-CoA hydratase uses H2O to remove double bond and create -OH group on beta carbon

3. B-hydroxyacyl-CoA dehydrogenase remove H from -OH group making an ester at beta carbon producing NADH

4. thiolase cleaves the 2C-CoA end (making acetyl-CoA) and add CoA to the rest of the chain

step 1 of B-oxidation

Dehydrogenation

palmitoyl-CoA + FAD = trans-enoyl-CoA + FADH2

acyl-CoA dehydrogenase

step 2 of B-oxidation

hydration

trans-enoyl-CoA + H2O = B-hydroxyacyl-CoA

enoyl-CoA hydratase

step 3 of B-oxidation

dehydrogenation

B-hydroxyacyl-CoA + NAD = NADH + B-ketoacyl-CoA

B-hydroxyacyl-CoA dehydrogenase

step 4 of B-oxidation

Thiolysis

B-ketoacyl-CoA + CoA-SH = acetyl-CoA + C14-acyl-CoA

thiolase

*hydrolysis but instead of water, thiol group break down bond so remaining fatty acid chain remains attached to CoA and can enter next B-oxidation cycle again

(n/2)-1

number of B-oxidation cycle needed

• n = #C in fatty acid

n/2

number of acetyl-CoA generated 

• 2C carbon unit

4 ATP per cycle

Number of ATP generated by B-oxidation only (aka fatty acid to acetyl-CoA)

1.5

FADH2 leads to __ ATP

2.5

NADH leads to __ ATP

10

TCA cycle leads to one FADH2 and three NADH and 1 GTP, which turns out to be __ ATP molecules produced when going through the ETC

= (4*# of cycles) + (10*# of acetyl-CoA generated)

number of ATP molecules generated by ENTIRE oxidation of fatty acid to CO2 and H2O

mobilization of storage fats

1. Glucagon and epinephrine are major hormones to activate adenylyl cyclase on the membrane of adipocytes, leading to elevation in cAMP and activation of the cAMP-dependent protein kinase PKA;

2. .PKA phosphorylates perilipin, a family of proteins around the lipid droplets, and PKA phosphorylates and activates hormone-sensitive lipase as well;

3. These phosphorylation events change the conformation of perilipin, allowing access of the activated lipases to triacylglycerols within the lipid droplets;

4.  Triacylglycerols are hydrolyzed and free fatty acids are released to the blood;

5.  Fatty acids are bound to albumin and carried to the target tissues for oxidation or re-esterification.