Beta oxidation

Question 1

What is Step 2 of Beta Oxidation

Answer 1

• 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

Question 2

How are fatty acids prepared for catabolism?

Answer 2

• 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

Question 3

Where does beta oxidation take place

Answer 3

matrix of mitochondria

Question 4

What is Step 1 of Beta oxidation

Answer 4

• 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

Question 5

What is an overview of the Beta Oxidation Pathway?

Answer 5

• 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*

Question 6

What is the enzyme involved in fatty acid activation

Answer 6

acyl-CoA synthetase

• inorganic phosphatase (to convert pyrophosphate into 2Pi)

Question 7

What is Beta hydroxyacyl CoA dehydrogenase used for

Answer 7

Step 3 beta oxidation

• uses NAD+ as cofactor

Question 8

What is compartmentalization

Answer 8

• 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

Question 10

How are fatty acids transported into mitochondrial matrix?

Answer 10

• 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

Question 11

What is Enol-CoA hydratase used for?

Answer 11

Step 2 of Beta oxidation

Question 12

What is the intermediate of fatty acid activation

Answer 12

acyl adenylate

Question 13

What is Step 4 of Beta oxidation?

Answer 13

• 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

Question 14

What is step 3 of Beta oxidation

Answer 14

• 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

Question 15

What is the overall stoichiometry for oxidation of palmitoyl CoA (C16:0) thorugh beta oxidation

Answer 15

Question 16

What is Acyl CoA dehydrogenase for?

Answer 16

• step 1 beta oxidation
• used cofactor FAD

Question 17

How are fatty acids activated

Answer 17

• 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

Question 18

What is the product of Beta oxidation

Answer 18

• each round produces an acetyl CoA and shortens chain by two carbons
• beta oxidation is repeated until all carbon atoms in fatty aicd are released as acetyl CoA
• complete oxidation of palmitic acid (C16) into eight molecules of acetyl CoA, requires 7 passes
• 1 FADH2 is formed in each turn (7 FADH2 in total)
• 1 NADH is formed in each turn (7 NADH in total)
• Acetyl CoA enters citric acid cycle and is furthr oxidized into CO2, making more GTP, NADH and FAHD2