Beta Oxidation Ctto

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LIPID METABOLISM-

Beta oxidation and ketogenesis

Dr. Hariharan, V
Assistant professor,
Department of Biochemistry,
Karpagam Faculty of Medical Sciences and Research,
Coimbatore.

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Free Fatty Acids
 Free fatty acids are fatty acids in blood in
unesterified state
 Longer chain FA are bound to albumin
and transported to many tissues
 Shorter chain FA exist without attached
to albumin
 The FA must enter mitochondria for
oxidation

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Preparatory Step 1: activation of FA
 Before oxidation the fatty acids must be
activated. This occurs in the cytosol
 Acyl CoA synthase which is a kinase
enzyme attaches a CoA to the fatty acid
making it Acyl CoA
 This is the only step requiring ATP. Two
high energy bonds of ATP is utilised, so it
becomes AMP + PPi, ensuring that the
overall reaction proceeds forward
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Preparatory Step 2: entering
Mitochondria
 Carnitine (beta hydroxy gamma trimethyl
ammonium Butyrate) is widely distributed in
the body and has a role like vitamin
 Acyl CoA cannot penetrate Inner
Mitochondrial membrane
 Carnitine Palmitoyl Transferase (present in
outer mito membrane) – I converts acyl Coa
A to Acyl Carnitine Acyl Carnitine
permeates mitochondrial membrane by
Carnitine translocase CPS- II (present in
inner mitochondrial membrane) converts it
back to Carnitine and ACYL CoA
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Overall reactions of beta oxidation

 Two Carbons at a
time are cleaved
from fatty acid as
acetyl CoA at
carboxyl end. The
chain is broken
between alpha and
Beta Carbon, so the
name beta oxidation
 Palmitoyl CoA ( 16
C) produces 8
Acetyl CoA
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Step 1: removal of 2 H

 Two H atoms from alpha and Beta Carbon


are removed by acyl CoA dehydrogenase
and accepted by FAD
Step 2: addition of water

 Δ2 enoyl CoA hydratase adds water to


saturate the double bond to form 3-hydroxy
acyl CoA
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Step 3: dehydrogenation

 3-hydroxyacyl CoA dehdrogenase removes


2H atoms using NAD to form 3-keto acyl
CoA
Step 4: splitting

 Thiolase (3-keto acyl CoA Thiolase) split 3-


ketoacyl CoA at 2,3 position forming Acetyl
CoA and acyl CoA which is 2C less

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Step 5
 The acyl CoA which is 2C less reenters at
step 1 to become completely oxidized in
a step wise manner to form acetyl CoA
 All these acetyl CoA enters TCA cycle to
give energy
 FA oxidation is strategically located inside
Mitochondria so that Acetyl CoA can
enter TCA cycle and Reducing equivalens
can be converted to ATP by ETC
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Regulation

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Oxidation Odd cahin FA
 Even chain fatty acids forms acetyl CoA.
FA containing odd number of Carbons
produces many acetyl CoA and one
Propionyl CoA( 3C)
 This is convereted to Succinyl CoA
 It enters TCA cycle

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Energetics
 One cycle of Beta oxidation produces
one NADH2 and 1 FADH2 . They enter
ETC producing 5 ATPs (old calculation).
 Palmitic acid undergoes seven cycles= 7 x
5= 35 ATP
 Palmitic acid= 16 C= 7 cycles= 8 acetyl
CoA = 8 x 12 = 96 ATP
 Total 35 + 96 = 131 ATP. 2 ATP consumed
for acyl CoA synthase=> 129 ATPs
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Oxidation of VLCFA
 Very long chain FA (C20, C22) are
oxidised by peroxisomes.
 It produces acetyl CoA and Hydrogen
peroxide
 H2O2 broken down by catalase to water

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Oxidation of unsaturated FA

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Clinical Aspects
1. Carnitine deficiency: sometimes occur in
newborn- especially in preterm infants-
due to inadequate synthesis of renal
leakage. It can also accur in chronic renal
failure patients undergoing
HemoDialysis. Hypoglycemia due less
beta oxidation and lipid accumulation,
muscular weakness
treatment- oral carnitine
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Why hypoglcemia?
Usually when blood glucose level falls, FA
oxidation produces acetyl CoA and
ketone bodies which provides energy, so
not all the blood glucose is used up, so
blood glucose remains normal
 But When FA oxdn is defective, all blood
glucose is utilized hypoglycemia

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2. CPT-1 deficiency

 Affects only liver- reduced FA oxidation and


ketogenesis- hypoglycemia

3. CPT-2 deficiency

 Affects skeletal muscle and when severe liver


also affected

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4. Diabetic drugs

 Sulfonylureas( glibenclamide, Glimepiride]


also inhibits CPT I hypoglycemia
5.Acute fatty liver of pregnancy

 Deficiency of short chain acyl CoA


dehydrogenase

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6. Jamaican vomiting sickness

 Eating unripe fruit of AKEE tree it has


hypoglycin inhibits short and medium
chain acyl coA dedrogenase
7.hypoglycemia
Dicarboxylic aciduria

 Medium chain acyl coA dehdrogenase


deficiency hypoglycemia. Urine contains
ωdiacrboxylic acids
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8. Refsum’s disease

 Some plan food stuff contain Phytanic


acid blocks beta oxidation neurologic
9. Zellweger
disorder syndrome

 Cerebrohepatorenal syndrome- absence of


peroxisosmes long chain FA
accumulate(C26-38).

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References
 Harper

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