Beta oxidation Flashcards
What is Step 2 of Beta Oxidation
- water is added across double bond
- produced alcohol at btea carbon
- hydration of alkene to alcohol
Begins with : Trans Δ^2 Enol CoA
Enzyme: Enol CoA hydratase
Cofactor: none only H2O added
Produces: L-B- Hydroxy acyl CoA
How are fatty acids prepared for catabolism?
- activating them to fatty acyl CoA
Fatty Acid + CoA +ATP -> Fatty Acyl-CoA + AMP + PPi
PPi -> 2Pi
NET RXN: Fatty Acid + CoA +ATP -> Fatty Acyl-CoA + AMP + 2Pi
-higherly endergonic reaction
*thioester bond, high energy bond so need ATP to create the bond
Note: conversion of one mole of ATP to AMP +2Pi is equivalent to hydrolysis of 2 moles of ATP to ADP +Pi
Where does beta oxidation take place
matrix of mitochondria
What is Step 1 of Beta oxidation
- oxidation by FAD
- forms double bond between alpha and beta carbons of fatty acyl CoA (Alkance to Alkene)
Starts with : Palmitoyl CoA
enzyme: oxidoreductase called acyl CoA dehydrogenase
Cofactor: FAD ->FADH2
Produces: Trans Δ^2 Enoyl CoA
*trans makes is “enoic acid”
* note why are we using FAD
What is an overview of the Beta Oxidation Pathway?
- fatty acyl CoA molecules once in mitochondrion are committted to undergo beta oxidation
- occurs in 4 steps: Oxidation, hydration, oxidation, thiolysis
- each pass thorugh beta oxidation removes one acetyl moiety in form of acetyl CoA,
*if start with 16 carbon fatty acid, goes thorugh beta oxidation and get 14 fatty acid and actyl CoA*
What is the enzyme involved in fatty acid activation
acyl-CoA synthetase
- inorganic phosphatase (to convert pyrophosphate into 2Pi)
What is Beta hydroxyacyl CoA dehydrogenase used for
Step 3 beta oxidation
- uses NAD+ as cofactor
What is compartmentalization
- beta oxidation takes place in mitochondrial matrix
- outer mitochondrial membrane is freely permeable to small molecules and ions
- inner mitochondrial membrane is highly impermeable to most solutes
- matrix has differy chemical position from bulk of cytosol
How are fatty acids transported into mitochondrial matrix?
- if smaller than 12 carbonds can pass in freely into inner mitochondrial membrane
- if larger than 12 carbons transported via acyl carnitine/ carnitine transporter in form on Fatty acyl carnitine esters
- acyl CoA is not able to travel thorugh with carnitine
- uses CoA from the matrix
*if deficiency of carnitine fatty acid oxidation will not occur
What is Enol-CoA hydratase used for?
Step 2 of Beta oxidation
What is the intermediate of fatty acid activation
acyl adenylate
What is Step 4 of Beta oxidation?
- lysis of bond between alpha and beta carbons (thiolysis)
- all this was to break this carbon carbon bond (had to be oxidized to a ketone)
*Overall goal is to synthesise ATP
Begins with: B-Ketoacyl CoA
Enzyme: thiolase
Cofactor: CoAS- and H+
Produces: myristoyl CoA and Actyl CoA
What is step 3 of Beta oxidation
- oxidation by alcohol and NAD+
Starts with: L-B- Hydrozy acyl CoA
Enzyme: B-hydroxyacyl CoA dehydrogenase
Cofactor: NAD+ -> NADH + H+
produces: B ketoacyl CoA
What is the overall stoichiometry for oxidation of palmitoyl CoA (C16:0) thorugh beta oxidation
How are fatty acids activated
- two step process
Step 1
- nucleophilic oxygen atom of the fatty acid (nucleophile) attacks the alpha phosphate of ATP (electrophile) forming PPi and an acyl adenylate.
- PPi is immediatly hydrolyzed to 2Pi
Step 2
- Thiolate anion fromm of coenzyme A, as nucleophile, reacts with the acyl adenylate
- AMP is the leaving group and fatty acid acyl- CoA thioester is formed
- Delta G for reaction is -15, but breaking pyrophosphate releases -19 kJ/mol therfore overall delta G = -34 kJ/mol
