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Chapter 23:Fatty AcidCatabolism (Freeing of FA From triglycerides (Hormone…
Chapter 23:
Fatty Acid
Catabolism
Freeing of FA
From triglycerides
Hormone Activation
Adrenyline
ATCH
Glucagon
Signal Pathway
A.
Activation of pathway
B.
Adenylyl cyclase make cAMP
C.
cAMP activate PKA
D.
PKA activates triacylglycerol lipase
E.
Lipase is dependent on bile salts
F.
(Pancreatic) Lipase removes the FA at C-1 & C-3
G.
Additional lipases and esterases remove the C-2 FA
L.
Long FA are secreted as chylomicrons through the blood stream and transported by serum albumin to the heart, muscle, and liver to β-oxidation.
S.
Short FA are absorbed directly into the villi and into the intestinal mucosa
β.
β-oxidation
Mapped pathway
FA Activation and Transportation into
the Mitochondria for β-oxidation
Short FA
Acitvation
Occurs within the
Mitochondria's matrix
Enzyme
: acyl-CoA synthetase
Transportation:
accepted directly into the mitochondria matrix
Long FA
Activation occurs on the
Mitochondria's outter membrane
Occurs within the
Mitochondria's matrix
Enzyme
: acyl-CoA synthetase
Transport into the Mitochondria
3 principle enzymes
Carnitine acyltransferase II
Carnitine acyltransferase I
produces
O
-acylcarnitine from FA acyl-CoA and L-carnitine
and transports
O
-acylcarnitine into the intermembrane space
Carnitine: acylcarnitine translocase
Transports
O
-acylcarnitine into the mitochondria matrix
Substrates
FA acyl-CoA
L-Carnitine
Products
FA acyl-CoA
#
L-carnitine
#
O
-acylcarnitine
#
β-Oxidation
Saturated FA
Even #-C
Length of the FA determines the
location of β-oxidation
'# Carbons < 14-C
mitochondria matrix
14+ Carbons
mitochondria membrane enzyme complex
Once short enough the FA acyl may
move to the mitochondria matrix
#
Step 1: Oxidation
Enzyme
Four types of acyl-CoA dehydrogenases
Long chain acyl-CoA dehydrogenase
LCAD
Medium chain acyl-CoA dehydrogenase
MCAD
Very long chain acyl-CoA dehydrogenase
VLCAD
Homodimer
Short chain acyl-CoA dehydrogenase
SCAD
:!:
acyl-CoA dehydrogenases contain a non-covalently bound FAD that is reduced during the oxidation of the FA acyl
Reduces FADH2 passes electrons to ETF (electron transfer flavoprotein)
ETF sends the electrons to Q in the ETC
:!:
Reaction:
Creates a double bond between the α- and β-carbons
Substrate
Fatty acyl-CoA
Product
trans
-Δ2-Enoyl-CoA
Step 2: Hydration
Enzyme
Enoyl-CoA hydratase
(a.k.a. crotonases)
:!:
Reaction:
Adds water across the double bond
Substrate
trans
-Δ2-Enoyl-CoA
#
Product
L-β-Hydroxyacyl-CoA
Step 3: Oxidation
Enzyme
L-Hydroxyacyl-CoA
Dehydrogenase
Requires the use of NAD+
as a coenzyme
:!:
Reaction:
Oxidation of the hydroxyl group at the β-position
Substrate
L-β-Hydroxyacyl-CoA
#
Product
β-Ketoacyl-CoA
Step 4: Cleavage
Enzyme
Thiolase
:!:
Reaction:
Cleavage between the α- and β-carbons
Substrate
β-Ketoacyl-CoA
#
Product 1
acetyl-CoA
:warning: Goes to the TCA cycle
Product 2
Fatty acyl-CoA minus 2-C
:warning: Starts back through the process.
Odd #-C
:warning: Will go through β-oxidation the same however, the final product will be a 3-C propionyl-CoA instead of Acetyl-CoA
Breaking Down propionyl-CoA
Step 1:
Reactants
Propionyl-CoA
ATP
Products
D-Methylmalonyl-CoA
Enzyme
: Propionyl-CoA Carboxylase
Step 2:
Enzyme:
Methylmalonyl-CoA epimerase
Products
L-Methylmalonyl-CoA
Reactants
D-Methylmalonyl-CoA
#
Step 3:
Enzyme:
Methylmalonyl-CoA
Products
Succinyl-CoA
Reactants
L-Methylmalonyl-CoA
#
Unsaturated FA
Will go through the β-oxidation process until the
double bond is at the β-C
One new
enzyme
: Enoyl-CoA Isomerase
Makes the
cis
-Δ2-enoyl-CoA into a
trans
-Δ2-enoyl-CoA.
:warning: Then it may be able to continue β-oxidation from
trans
-Δ2-enoyl-CoA.
Ketone Bodies
Homotetramers
#
#
#