Fatty Acid Breakdown and Ketone Bodies

Question 1

Describe two pathways that fatty acids in adipose tissue can follow.

Answer 1

. 1 FAs can be esterified to glycerol, 3 FAs esterified to triacylglycerol
. FAs can undergo beta-oxidation in mitochondria to form acetyl CoA

Question 2

Which tissues can oxidise FAs? Which tissues cannot?

Answer 2

. FAs can be oxidised by the liver and muscles

. Can’t be oxidised by brain (due to blood brain barrier)and erythrocytes (due to no mitochondria)

Question 3

Which hormones stimulate the metabolism of FFAs?

Answer 3

Glucagon and adrenaline

Question 4

Describe the processes that occur when glucagon and adrenaline activate fatty acid breakdown.

Answer 4

. Glucagon/adrenaline activate hormone-sensitive lipase
. Hormone-sensitive lipase hydrolyses TAGs in adipose to produce glycerol and FFAs

. FFAs released into circulation, bound to plasma albumin, and travel to target cells e.g. skeletal muscle cells
. In skeletal muscle cells, FFAs undergo beta-oxidation to form acetyl CoA, which enters the TCA cycle to eventually produce ATP

. Glycerol is transported to the liver, converted to glycerol-3-phosphate, then to DHAP
. DHAP used in glycolysis or gluconeogenesis to yield ATP/glucose

Question 5

Name the products generated by beta-oxidation of fatty acids.

Answer 5

Acetyl CoA, NADH, FADH2

Question 6

What happens during beta-oxidation of fatty acids? What is the importance of carnitine in this process?

Answer 6

. LCFAs activated in cytosol to form thiol esters with CoA (uses ATP)
. LCFAs transported to mitochondria for beta-oxidation
. However, CoA esters can’t cross inner mitochondrial membrane, so carnitine is required
. LCFA group of thiol ester transferred to carnitine, and complex crosses inner mitochondrial membrane into mitochondrial matrix
. LCFA group rejoins with CoA in the matrix and now can undergo beta-oxidation in mitochondrion
. (Small/medium FAs can just cross the IMM without carnitine)

Question 7

How is carnitine obtained?

Answer 7

From meat in the diet

Question 8

Where is carnitine synthesised?

Answer 8

Synthesised by liver and kidney, transported from kidney to muscles via blood

Question 9

What is the main problem that carnitine deficiency causes?

Answer 9

Build up of toxic LCFAs can lead to neurological damage

Question 10

What is the role of malonyl CoA in the regulation of beta oxidation of fatty acids?

Answer 10

. Malonyl CoA inhibits CPTI (carnitine palmitoyltransferase I), which means that LCFAs can’t be transported into the mitochondria to undergo beta-oxidation

Question 11

How are fatty acid synthesis and fatty acid oxidation linked?

Answer 11

They are linked reciprocally

Question 12

Where are ketone bodies synthesised?

Answer 12

In mitochondria in the liver

Question 13

Name the three ketone bodies formed.

Answer 13

Acetoacetate, b-hydroxybutyrate, acetone (can’t be used, excreted in breath)

Question 14

What happens to acetoacetate and b-hydroxybutyrate?

Answer 14

. Acetoacetate is converted to acetyl CoA and enters the TCA cycle
. b-hydroxybutyrate is oxidised to acetoacetate, which is then converted to acetyl CoA to enter the TCA cycle

Question 15

Ketone bodies are especially important for which organ during starvation?

Answer 15

The brain, as brain can’t use FFAs because FFAs are bound to albumin, which is too large to cross the blood brain barrier

Question 16

Why can babies quickly become ketotic?

Answer 16

They have small glycogen stores

Question 17

Which organs can use ketone bodies?

Answer 17

. Brain adapts to use ketone bodies during starvation
. Heart and kidneys preferentially use ketones under all conditions to spare glucose
. Liver can’t metabolise ketone bodies

Question 18

What is the effect of using ketone bodies on protein breakdown?

Answer 18

Lots of ketone bodies means reduced protein breakdown in muscle during starvation

Question 19

What is the normal plasma concentration of ketone bodies?

Answer 19

0.1 mM

Question 20

What is ketonuria and under what conditions does it occur?

Answer 20

. Ketonuria is when ketones are excreted in the urine
. Occurs when blood concentration of ketones is above 7 mM, as utilisation of ketones by tissues is saturated
. E.g. in uncontrolled diabetes this can happen often

Question 21

When does ketoacidosis occur?

Answer 21

. When there’s lots of acidic ketones (acetoacetate and acetone, not b-hydroxybutyrate) in the blood
. This causes the blood pH to drop, which can be life-threatening.

Question 22

How can ketonuria/ketoacidosis be detected?

Answer 22

. Detected with ketotest (dipstick with colour changes)

. Ketotest colour changes quite subtle, so can confirm with Acetest

Question 23

Can we make glucose from triacylglyerol?

Answer 23

Yes, we can make a bit from glycerol (glycerol is converted to glycerol-3-phosphate, then to DHAP, and enters gluconeogenesis just before F16BP is converted to F6P)

Question 24

Can we make glucose from FFAs?

Answer 24

No, because FFAs undergo beta-oxidation to form acetyl CoA and acetyl CoA cannot form glucose (no step/enzymes in gluconeogenesis allow this conversion)

Question 25

Which molecule are ketone bodies synthesised from?

Answer 25

Acetyl CoA