Fatty acid catabolism Flashcards

Question

How are FA activated?

Answer 1

Fatty acyl-CoA synthetase firstly uses ATP to charge a FA This charged ATP- fatty acyl-adenylate is attached to thiol group of coenzyme A by fatty acyl-CoA synthetase forming thioester fatty acyl-CoA

Answer 2

To synthesize longer membrane lipids | Beta-oxidation

Answer 3

Mitochondria

Answer 4

- Small (< 12 carbons) FA diffuse freely across mitochondrial membranes - Longer fatty acids are transported

Answer 5

Fatty acyl–CoA esters formed at the cytosolic side of the outer mitochondrial membrane

Answer 6

carnitine transport system

Answer 7

When fatty acyl-CoAs are destined to be transported into mitochondria, they are attached to hydroxyl group of carnitine to form fatty acyl–carnitine This transesterification is catalyzed by carnitine acyltransferase I (I as it in the outer membrane) This enzyme removes Acetyl CoA and attaches carnitine Fatty acyl-carnitine passes into intermembrane space through large pores in the outer membrane (moves from cytosol to the intermembrane space) The fatty acyl–carnitine ester then enters the matrix by facilitated diffusion through the acyl-carnitine/carnitine transporter of the inner mitochondrial membrane (moves from intermembrane space to matrix) Carnitine acyltransferase II (in the matrix) then transfers fatty acyl group from carnitine to intramitochondrial coenzyme A Carnitine acyltransferase II regenerates fatty acyl–CoA and releases it, along with free carnitine, into the matrix Fatty acyl-CoA is now available for b-oxidation Carnitine reenters the intermembrane space via the acylcarnitine/carnitine transporter.

Answer 8

three-step process for transferring fatty acids into the mitochondrion—esterification to CoA, transesterification to carnitine followed by transport, and transesterification back to CoA—links two separate pools of coenzyme A and of fatty acyl–CoA, one in the cytosol, the other in mitochondria.

Answer 9

Coenzyme A in the mitochondrial matrix is largely used in oxidative degradation of pyruvate, fatty acids, and some amino acids, whereas cytosolic coenzyme A is used in the biosynthesis of fatty acids

Answer 10

Conversion to the carnitine ester commits the fatty acyl to the oxidative fate

Answer 11

more carnitine, more FA can be transported

Answer 12

In b-oxidation there are 4 reactions and 4 enzymes

Answer 13

At each cycle of b-oxidation there is a product of Acetyl CoA

Answer 14

1) Dehydrogenation of fatty acyl–CoA produces a double bond between the alpha and beta carbon atoms (C-2 and C-3), yielding a trans-Δ2-enoyl-CoA- acyl-CoA dehydrogenase. The electrons removed from the fatty acyl–CoA are transferred to FAD-> FADH 2) In the second step of the β-oxidation cycle water is added to the double bond of the trans-Δ2-enoyl-CoA to form the L-stereoisomer of β-hydroxyacyl-CoA (3-hydroxyacyl-CoA)- enoyl-CoA hydratase 3) In the third step, L- β-hydroxyacyl-CoA is dehydrogenated to form β-ketoacyl-CoA, by the action of β-hydroxyacyl-CoA dehydrogenase. NAD+ is the electron acceptor. The NADH formed in the reaction donates its electrons to NADH dehydrogenase, an electron carrier of the respiratory chain, and ATP is formed from ADP as the electrons pass to O2. The reaction catalyzed by β-hydroxyacyl-CoA dehydrogenase is closely analogous to the malate dehydrogenase reaction of the citric acid cycle- 4) The fourth and last step of the β-oxidation cycle is catalyzed by acyl-CoA acetyltransferase, more commonly called thiolase, which promotes reaction of β-ketoacyl-CoA with a molecule of free coenzyme A to split off the carboxyl-terminal two-carbon fragment of the original fatty acid as acetyl-CoA. The other product is the coenzyme A thioester of the fatty acid, now shortened by two carbon atoms

Answer 15

β-oxidation occurs at carboxyl end

Answer 16

β-oxidation of 16 carbon FA yields: 8Acetyl-CoA, 7FADH2, 7NADH, 7H+ 1.5 ATP/FADH2 and 2.5 ATP/NADH-> 8Acetyl-CoA, 28ATP, 7H2O

Answer 17

``` # of AcetylCoA= #C/2 # of FADH, NADH, H+= #C/2-1 ATP=(FADH+NADH)*4 ```

Answer 18

B-oxidation occurs normally until double bond is encountered between carbons 3 and 4 They require additional enzyme 3,2-enol-CoA isomerase which transfers double bond to the carbons 2,3 from 3,4- The double bond is available- B-oxidation occurs smoothly

Answer 19

Between carbon 2 and 3

Answer 20

enzyme 3,2-enol-CoA isomerase transfers double bond to the carbons 2,3 from 3,4 Reversible reaction

Answer 21

One FADH2 less is produced as double bond didn't have to be created between carbons 2 and 3 - was already there -1st step of b-oxidation was skipped

Answer 22

2,4-dienoyl-CoA uses NADH to change cis conformation (not suitable for b-oxidation) to trans

Answer 23

3 carbon compound- propionyl CoA is formed in the last step of b-oxidation It goes through reactions forming succinyl-CoA in the end (TCA) Vitamin B12 is important in situations when cells encounter odd number FA This doesn’t occur often

Answer 24

In bactria, Enz1 and 3 are the ones that creates energy molecules in the form of FADH and NADH

Answer 25

Short chain specific enzymes float around | Long chain specific enzymes are imbedded in cell membrane

Answer 26

Regulated by both transcription factors (e.g. PPARg) and kinases (e.g. AMPK)

Answer 27

Fatty acyl-CoA synthesized in the cytoplasm is directed to β-Oxidation or TG synthesis

Answer 28

Carnitine Shuttle is the point of commitment to β-Oxidation

Answer 29

Malonyl-CoA, the first intermediate of FA synthesis, inhibits Carnitine Acetyltransferase I Malonyl-CoA is necessary for FA synthesis-> inhibits beta-oxidation process

Answer 30

Low ATP (low ATP/AMP ratio) stimulates AMPK leading to activation of Carnitine shuttle

Answer 31

High NADH/NAD+ ratio inhibits Acyl-CoA dehydrogenase

Answer 32

AMP kinase senses the amount of AMP

Answer 33

First enzyme of b-oxidation which creates an energy molecule - FADH2

Answer 34

HIGH ENERGY LEVELS

Answer 35

Oxidation of ω carbon of FAthe carbon most distant from the carboxyl group Happens in endoplasmic reticulum in liver and kidney A rare event

Answer 36

Inβ-oxidation enzymes | act at the carboxyl end of a fatty acid

Answer 37

in the endoplasmic reticulum of liver and kidneys | preferred substrates are fatty acids of 10 or 12 carbon atoms.

Answer 38

FA with carboxylic group at both ends is then broken down to Succinate and Adipic acid- yielding Acetyl CoA from both ends

Answer 39

- Acetone- usually maintained at low concentrations. Exhaled through respiration. Acetone smell is a sign of ketosis. - Acetoacetate - B-hydroxybutyrate (BHB)

Answer 40

Acetoacetate and BHB

Answer 41

Ketogenesis (ketone body synthesis) occurs when we are not eating/starvation or diabetes

Answer 42

Mitochondria within hepatocytes is the site of ketogenesis

Answer 43

Extra acetyl-CoA

Answer 44

It can either enter the citric acid cycle or undergo conversion to the “ketone bodies,”

Answer 45

transported by the blood to tissues other than the liver (extrahepatic tissues), where they are converted to acetyl-CoA and oxidized in the citric acid cycle, providing much of the energy required by tissues

Answer 46

2 acetyl-CoA | It is the enzymatic condensation of two molecules of acetyl-CoA, catalyzed by thiolase

Answer 47

Thiolase is the last enzymes of b-oxidation and first of ketogenesis. It's reaction is reversible

Answer 48

2 Acetyl-CoA are converted into acetoacetyl-CoA by thiolase Acetoacetyl-CoA is converted into HMG-COA (B-Hydroxy-B-methylglutaryl-CoA) by HMG-CoA synthase which adds a 3rd Acetyl CoA to acetoacetyl-CoA HMG CoA is then lysed/cleaved to free acetoacetate (worth 2 ketone bodies) and acetyl-CoA by HMG-CoA lyase Acetoacetate can then be converted into Acetone and β-hydroxybutyrate

Answer 49

HMG-COA synthase is present in mitochondria as ketone body synthesis occurs there Its isoform is present in the cytoplasm - place a role in cholesterol synthesis - the only enzyme that is present both in cytoplasm and mitochondria

Answer 50

All are located in the mitochondria, but HMG-CoA which also has a cytoplasmic isoform (both in the cytoplasm and in the mitochondria)

Answer 51

Ketone bodies are converted to acetyl-CoA Once ketone bodies are made -> circulation-> taken up and have to be converted back to acetyl-CoA This starts with B-hydroxybutyrate B-hydroxybutyrate is oxidized to acetoacetate by D-B-hydroxybutyrate dehydrogenase The acetoacetate is activated to its coenzyme A ester by transfer of CoA from succinyl-CoA, an intermediate of the citric acid cycle in a reaction catalyzed by B-ketoacyl-CoA transferase. The acetoacetyl-CoA is then cleaved by thiolase to yield two acetyl-CoAs, which enter the citric acid cycle.

Answer 52

In ketone body catabolism transfers CoA from Succinyl-CoA to Acetoacetate to make Acetoacetyl-CoA ABSENT in the liver If it was present - ketone bodies would never leave the liver as they would have been made and instantly catabolised

Answer 53

Odd-number fatty acids are oxidized by the b-oxidation pathway to yield acetyl-CoA and a molecule of propionyl- CoA.