Fatty Acid Oxidation Flashcards
1
Q
Metabolism of fats
A
- Store fat in the body as Tri Acyl Glycerides (TAGs)
- Triglycerides – triesters of fatty acids and glycerol.
- Fatty acids can be of any type.
- Phospholipids (PL)
2
Q
Phospholipids (PL)
A
- Glycerol esterifed with two FAs; the third hydroxyl group of glycerol is linked by phosphate group to other molecules – the polar part of phospholipids – different classes of PL
3
Q
Triacylglycerides (TAG) as a source of fatty acids
A
- digested in the small intestine
- pancreatic lipase
- releases fatty acids and monoacylglycerol
- these diffuse into enterocytes (facilitated by bile salts) where TAG are resynthesised
4
Q
Enterocytes
A
- export TAGs and cholesterol as chylomicrons (a type of lipoprotein) first into lymph vessels (lacteals in the intestinal villi), then they reach the blood – used by tissues
- Adipose tissue cells – store TAGs
- Muscle tissue, liver cells and other tissues – use the FAs from TAGs as sources of energy
5
Q
Liver cells export what?
A
- Excess of nutrients (glucose, FA) is exported as TAGs in lipoprotein particles – VLDLs from liver to the adipose tissue cells (for storage) and muscle cells; liver cells also produce HDLs
- As TAG from VLDLs are used -> IDLs -> LDLs
6
Q
TAG breakdown
A
- TAG from chylomicrons hydrolysed in blood capillaries by Lipoprotein lipases (LPL) – attached to the outside of cells lining the capillaries – glycerol and free FA are produced and can enter the cells supplied by those capillaries
- Enzymes are Lipoprotein lipases LPL (hormone-sensitive).
- Insulin - increase adipocyte LPL and placement capillary endothelium, decreased muscle LPL
- glucagon, adrenalin - increase Muscle and Myocardial LPL
- When FA are released from adipose tissue cells (low insulin, high glucagon) – hormone sensitive lipase enzyme – free fatty acids (FFA) - transported by serum albumin to the cells that need them as source of energy (muscle, liver, etc – not brain – where the uptake of FFA is very slow due to the blood brain barrier)
7
Q
Activation of fatty acid
A
- Formation of fatty acyl-CoA
- Requires ATP hydrolysis
- Acyl-CoA synthetase (Thiokinase)
- ATP convert to AMP.
- AMP is substrate for Adenylate kinase: ATP is needed to phosphorylate to ADP – overall 2ATP molecules are required per molecule of FA activated
- occurs on the outer mitochondrial membrane
8
Q
B-oxidation strategy
A
- sequence of four reactions (4 steps) that removes a 2-Carbon atom fragment from the long hydrocarbonate chain of a fatty acid (an activated fatty acid – fatty acyl~CoA)
- 2-Carbon atom fragment is removed as Acetyl~CoA
- (n-2) fatty acyl~CoA produced undergoes another round of beta-oxidation steps until two Acetyl~CoA are formed in the last round
9
Q
Step 1 of b-oxidation
A
- formation of an enoyl-CoA (incorporation of a trans double bond).
- Enzyme, Acyl-CoA dehydrogenase requires FAD cofactor.
- FAD cofactor regenerated via the Electron Transport Chain (1.5ATP)
- Electron Transport Flavoprotein – transfers electrons to ubiquinone pool inner mitochondrial membrane
- Deficiency in medium chain acyl-CoA dehydrogenase – linked to SIDS (sudden infant death syndrome)
10
Q
Step 2 of b-oxidation
A
- formation of 3-L-hydroxyacyl-CoA
- Enzyme - Enoyl-CoA hydratase (various isoforms depending on FA length).
- Involves the addition of water across the double bond
11
Q
Step 3 of b-oxidation
A
- formation of b-Ketoacyl-CoA
- Enzyme – 3-L-hydroxyacyl-CoA dehydrogenase.
- Requires NAD+ - formation of C=O
12
Q
Step 4 of b-oxidation
A
- Cleavage of Ca-Cb bond – release of acetyl-CoA
- Enzyme – b-Ketoacyl-CoA thiolase.
- Requires an additional molecule of CoA.
- Acetyl-CoA enters TCA cycle, Fatty acyl-CoA renters oxidation pathway.
13
Q
Yield from b-oxidation
A
- a new FA CoA: 2 carbons shorter than parent
- 1 acetyl CoA (citric acid cycle)
- 1 NADH + H+
- 1 FADH2
14
Q
B-oxidation of unsaturated fatty acids
A
- Unsaturated fatty acid contain one or more cis C=C bonds
- Monunsaturated – 1 double bond
- Polyunsaturated – several double bonds
- Most contain first double bond between C9-C10 (D9).
- Additional double bonds occur at 3 carbon intervals
- Problem occurs at first double bond.
- Not a substrate for enoyl-dehydratase
- Requires bond rearrangement
15
Q
Convert from cis-3 bond to a trans-2 bond in b-oxidation
A
- Enzyme is Enoyl-CoA isomerase – changes the location of the double bond from C 3 and 4 (beta and gamma) to C 2 and 3 (alpha and beta)
- Now a substrate for Enoyl-CoA hydratase – another round of beta-oxidation takes place – and another;
- Then the first reaction of the next round introduces a C 2=3 double bond – but there is also a C4=5 double bond (D4 bond)
