Energy production: lipids

Question 1

List the fat-soluble vitamins

Answer 1

K,A,D,E

Question 2

Where is the glycerol from dietary triglycerides metabolised?

Answer 2

Liver

Question 3

Why do red blood cells not metabolise fatty acids?

Answer 3

They do not have mitochondria

Question 4

Why does the brain not metabolise fatty acids?

Answer 4

Fatty acids can not easily pass through the blood-brain barrier

Question 5

What hormones increase fatty acid mobilisation from adipose tissue?

Answer 5

Adrenaline and glucagon

Question 6

What hormone decreases fat mobilisation from adipose tissue?

Answer 6

Insulin

Question 7

How are fatty acids transported from adipose tissue to the consumer tissues?

Answer 7

Bound to albumin

Question 8

How would you describe the state of stored triglycerides in adipose tissue?

Answer 8

Dynamic state - they are constantly being broken down and recycled back to TAGs again

Question 9

What is the effect of low extracellular glucose on adipose tissue?

Answer 9

Low glucose uptake into the adipose tissue -> decreased synthesis of glycerol from glycolysis intermediates -> less TAG synthesis -> fatty acids build up in tissue -> released into blood as an alternative fuel

Question 10

What are some features of fatty acids?

Answer 10

Saturated or unsaturated

Amphipathic

Question 11

Why are some polyunsaturated fatty acids essential (i.e. required by diet)?

Answer 11

Because mammal cannot introduce a double bond beyond C9

Question 12

Name an essential fatty acid

Answer 12

Linolenic acid

Question 13

Where does fatty acid metabolism occur?

Answer 13

Mitochondria

Question 14

What has to happen to fatty acids before they can be transported into mitochondria?

Answer 14

They have to be activated by linking to coenzyme A, to create a high energy bond:
fatty acid + CoA + ATP -> fatty acyl CoA + AMP + 2Pi

Question 15

Which enzyme catalyses the linkage of CoA to fatty acids?

Answer 15

fatty acyl CoA synthase

Question 16

Activated fatty acids (fatty acly-CoA) do not readily cross the inner mitochondrial membrane. How are they transported across?

Answer 16

Carnitine shuttle:
Intermembrane space:
Carnitine + FA-CoA -> FA-Carnitine + CoA
Mitochondrial matrix:
FA-carnitine + CoA -> Carnitine + FA-CoA

Question 17

Which enzymes catalyse the transfer of fatty-acyl to carnitine and then back to CoA?

Answer 17

CAT1 and CAT2

Carnitine acyltransferases

Question 18

What is notable about the carnitine shuttle transporter?

Answer 18

It transports acetyl carnitine into the matrix whilst simultaneously transporting carnitine out of the matrix

Question 19

How is the carnitine shuttle regulated ( and therefore regulates the rate of FA oxidation?

Answer 19

Inhibited by malonyl-CoA (biosynthetic intermediate of FA synthesis)

Question 20

What do defects in the carnitine shuttle transport system cause?

Answer 20

Exercise intolerance and lipid droplets in muscle

Question 21

In fatty acid catabolism 2C (acetyl) is removed on each cycle producing which other products?

Answer 21

FADH2
NADH
H+

Question 22

What does fatty acyl-CoA require for catabolism to occur?

Answer 22

H2O (one per cycle)
FAD (one per cycle)
NAD+ (one per cycle)
CoA

Question 23

What are the products of fatty acid catabolism used for?

Answer 23

acetyl-CoA -> TCA cycle

FADH2 + NADH + H+ -> oxidative phosphorylation

Question 24

What happens to fatty acid oxidation in the absence of O2?

Answer 24

It stops as NAD+ and FAD are required in their oxidised forms for the fatty acid cycle

Question 25

Glycerol from adipose tissue or from enterocytes (dietary TAGs) can be transported to the liver in the blood. In the liver it is activated by what enzyme into glycerol phosphate?

Answer 25

Glycerol kinase

Question 26

What are the two metabolic routes that glycerol phosphate can go down in the liver?

Answer 26

Glycolysis: conversion to DHAP + NADH

TAG synthesis: esterification with fatty acyl-CoA

Question 27

Linkage of acetyl to CoA has what effect?

Answer 27

Creates a high energy of hydrolysis bond (linked via S-atom), therefore activates the acetyl group

Question 28

Why do we require vitmain B5 in our diet?

Answer 28

It cannot be synthesised in the body and is used in the synthesis of CoA

Question 29

Acetyl is an important intermediate in which anabolic and catabolic pathways?

Answer 29

1. Fatty acid synthesis (TAGs, phospholipids)
2. TCA cycle
3. HMG synthesis (ketone bodies, cholesterol (steroid hormones))

Question 30

Where are the three ketone bodies synthesised in the body?

Answer 30

1. Liver - acetoacetate and beta-hydroxybutyrate

2. Liver? blood - acetone (by non-enzymatic spontaneous decarboxylation)

Question 31

How is HMG-CoA synthesised?

Answer 31

From acetyl-CoA by HMG-CoA synthase (+ acetoacetly CoA)

Question 32

How are ketones synthesised from HMG-CoA

Answer 32

HMG-CoA lyase converts to acetoacetate. Acetoacetate can be spontaneously converted to acetone or enzymatically converted to beta-hydroxybutyrate

Question 33

How is cholesterol synthesised from HMG-CoA?

Answer 33

By the enzyme HMG-CoA reductase:

HMG-CoA -> Mevalonate -> cholesterol

Question 34

How do statins work?

Answer 34

Inhibit the enzyme HMG-CoA reductase and therefore the synthesis of cholesterol in the liver

Question 35

Why does increased fatty acid oxidation divert acetyl CoA into ketone body synthesis?

Answer 35

Fatty acid oxidation uses lots of NAD+ and therefore high levels can lower the [NAD+] (low substrate availability) and increase [NADH] (product inhibition) so much that it inhibits the two irreversible steps (isocitrate dehydrogenase and alpha-ketoglutarate dehydrogenase) of the TCA cycle. This causes acetyl CoA to be diverted from the TCA cycle into ketone body synthesis

Question 36

beta-hydroxybutyrate and acetoacetate are transported in the blood to tissues (with mitochondria). How are they used as fuel molecules?

Answer 36

Converted back to acetly CoA.

1. Acetoacetate -> acetyl CoA
2. Beta-hydroxybutyrate + NAD+ -> acetoacetate + NADH (and then converted to acetly CoA as in 1.)

Question 37

When does cholesterol synthesis occur?

Answer 37

When high insulin:glucagon ratio -> lyase inhibited, reductase activated

Question 38

When does ketone body synthesis occur?

Answer 38

When insulin: glucagon ratio low -> lyase activated, reductase inhibited
E.g. in starvation or diabetes

Question 39

What is the use of ketone bodies in starvation/diabetes?

Answer 39

Spares glucose (for brain) by converting fatty acids into ketone bodies in the liver which can then circulate in the blood and provide tissue with mitochondria acetly CoA for the TCA cycle.
Later on in starvation when glycogen stores have been depleted, protein will need to be broken down to produce glucose by gluconeogenesis

Question 40

How are fatty acid with an odd number of carbon atoms oxidised?

Answer 40

Beta-oxidation until 3C unit (proprionyl CoA), which can undergo:

1. Carboxylation by carboxylase -> methyl malonyl CoA (biotin cofactor)
2. Rearrangement by mutase -> succinyl CoA (Vitamin B12 cofactor)

Question 41

How do ketone bodies conserve glucose for utilisation in the brain?

Answer 41

Ketone bodies are converted to acetyl CoA which:

1. inhibits pyruvate dehydrogenase
2. inhibits PFK (via production of citrate in TCA cycle) -> [glucose-6-P] increases which:
   (i) inhibits hexokinase (product inhibition)

Question 42

What happens to the rate of lipolysis as ketone body concentration increases?

Answer 42

It decreases to conserve fatty acids