Lecture 8 - Fatty Acid Metabolism I

Question 1

fatty acid description and properties:

Answer 1

a molecule containing a long hydrocarbon tali (alkyl group) and a terminal carboxylate group

insoluble in water but soluble in an organic solvent

Question 2

palmitate:

Answer 2

type of fatty acid continuing a 15 hydrocarbon chain (alkyl group) and a terminal carboxylate group

Question 3

fatty acid activation (step one):

Answer 3

FA + ATP → acyl-adenylate

catalysed by: acyl-CoA-synthetase

Question 4

fatty acid activation (1):
(1) which enzyme?
(2) what does it do?
(3) what are the substrates?
(4) where in the structure is it activated?
(5) what is the final product in this process?

Answer 4

(1) acyl CoA Sythetase

(2) catalyses the covalent attachment of a (3) phosphorylation group of ATP (AMP)

(4) to the oxygen molecule of the carboxylate group of fatty acid, this reaction yields an acyl adenylate and a PPi

Question 5

fatty acid activation - step 2:

Answer 5

acyl adenylate + co-enzyme-A → Acyl-CoA

Question 6

fatty acid activation (2):
•Which enzyme?
•What does it do?
•What is the substrate(s)?
•Where in the structure is it activated?
•What is the final product in this process?

Answer 6

(1) acyl CoA synthetase
(2) replaces the AMP molecule of the acyl adenylate
(3) with a sulfhydryl group of co-enzyme-A
(5) this reaction gives one each of Acyl-CoA and AMP

Question 7

LO-1: Describe the process of FA activation by ATP and Co-EnzymeA to form acyl-CoA:

Answer 7

(1) fatty acid activation is an ATP consuming process to form acyl-CoA catalysed by an enzyme, acyl-CoA synthetase

(2) the fatty acid is first activated by ATP

(3) As a result, the carboxylate group of a Fatty acid is bound to the phosphoryl group of AMP to form an Acyl adenylate. The other phosphoryl groups of the ATP substrate are released as pyrophosphate (PPi)

(4) Subsequently, the oxygen molecule shared between AMP and an acyl adenylate is replaced by the sulfhydryl group of co-enzyme to form Acyl CoA. AMP is released.

Question 8

β Oxidation:

Answer 8

• 4 step process to release each 2C from Acyl CoA
•Acyl CoA (e.g. C16:0) are catabolised in 2C units
•First cleavage at β carbon

Question 9

LO2 - Describe the process of β-oxidation from acyl-CoA to acetyl-CoA:

Answer 9

1.Acyl-CoA dehydrogenase removes two hydrogen atoms between carbons 2 and 3, forming a trans enoyl-CoA and FADH2.

2.Water is added across the double bond by enoyl-CoA hydratase, forming 3-L-hydroxyacyl-CoA.

3.3-L-hydroxyacyl-CoA dehydrogenase removes hydrogen atoms from the 3rd carbon, forming 3-ketoacyl CoA, and generating NADH.

4.The terminal acetyl-CoA group is cleaved in a thiolysis reaction with CoA catalysed by b-ketothiolase (thiolase), forming a new acyl-CoA that is two carbons shorter than the previous one.

Question 10

LO4 - Explain the metabolic states in which ketone bodies are made:

Answer 10

•3 Acetyl CoAs are joined to form ketone bodies

•Acetoacetate and β hydroxybutyrate are used as fuel

•Acetone is lost in breath/sweat/urine and not respired

Question 11

LO3 - explain the metabolic states in which ketone bodies are made:

Answer 11

(1) under conditions of prolonged fasting or diabetes oxaloacetate is consumed to form glucose

(2) this reduces the availability of oxaloacetate in the TCA cycle resulting in accumulation of acetyl-coA

(3) When Acetyl CoA builds up in the liver beyond the capacity of the TCA cycle to consume it, ketone bodies are made

(4) these are released into the blood and used as fuels by other cells especially in the cardiac muscle cells and in the renal cortex

Question 12

degradation of odd-chained fatty acids:

Answer 12

some fatty acids have an odd number of carbons, those end up with 3-carbon CoA which is known as propionate CoA, proprionyl CoA enters the TCA cycle after being converted to succinyl CoA

Question 13

fatty acid catabolism summary:

Answer 13

(1) 2 carbons in the form of acetyl-CoA are removed from the FA in every cycle of beta-oxidation

(2) 1 molecule each of NADH & FADH2 are released in every cycle of beta-oxidation yielding 4 molecules of ATP per cycle

Question 14

depredation of unsaturated FA:

Answer 14

• mono-unsaturated fatty acids such as palmitoleate are transported across the mitochondrial inner membrane, just like saturated fatty acids
• on the mitochondrial outer membrane, mono-unsaturated palmitoleate is activated with ATP and co-enzyme A by acyl CoA synthetase to give palmitoleoyl CoA
• Palmitoleoyl CoA undergoes 3 rounds of beta-oxidation inside mitochondria