Energy Production: Lipids

Question 1

Describe some lipid characteristics, what do they derive from?

Answer 1

Structurally diverse, generally insoluble/hydrophobic, most contain C H O (phospholipids contain P&N), more reduced than carbohydrates so release more energy when oxidised and complete oxidation requires more oxygen.
Either fatty acid derivatives or hydroxy-methyl-glutaric acid (HMG) derivatives (including water soluble ketone bodies, cholesterol and vitamins.

Question 2

Fill in the blanks:
Hydroxy-methyl-glutaric acid has ____ carbons. It’s derivative, ketone bodies have ___ carbons. Other derivatives include cholesterol, used in _____ salts and the fat soluble vitamins: __, __, __ and __.

Answer 2

6
4
Bile
A, D, E and K.

Question 3

How are triacylglycerols stored, why and when are they used?

Answer 3

As they are hydrophobic, they’re stored in an anhydrous form in specialised adipose tissue. Triacylglycerols are utilised in prolonged exercise/starvation/pregnancy. Storage and utilisation are under hormonal control.

Question 4

What occurs in stage 1 of lipid metabolism and where?

Answer 4

Lipids/triacyglycerol –> glycerol + fatty acids, extracellularly in the GI tract, with the hydrolysis in the small intestine by pancreatic lipases.

Question 5

What is the function of chylomicrons?

Answer 5

Lipoproteins that transport triacylglycerol after it has been recombined from its products in the epithelial cells.

Question 6

In consumer tissues, fatty acid oxidation leads to energy release, which cells do not contribute to consumer tissues?

Answer 6

Red blood cells as they don’t contain mitochondria, white blood cells or the brain,since fatty acids don’t pass easily through the blood-brain barrier.

Question 7

What happens to the lipid in adipose tissue under hormonal stimulation?

Answer 7

Fatty acids stored as triacylglycerol in adipose tissue, is allowed to be mobilised by adrenaline/glucagon, which allows it to be transported by fatty acid albumin to consumer tissues.
Fatty acids are released into circulation via the lymphatics.

Question 8

Fill in the blanks:
Triacylglycerol/fatty acid cycle in _____ tissue breaks it down. Glycerol goes into _____ and glycerol-1-phosphate from _____ of transported glucose joins to reesterified _____.

Answer 8

Adipose
Blood
Glycolysis
Fatty acyl-CoA

Question 9

Why does low extracellularly [glucose] result in fatty acid release?

Answer 9

As an alternative fuel.

Question 10

Fatty acids may be saturated or unsaturated, they are amphipathic and certain polyunsaturated fatty acids are essential. What does this mean?

Answer 10

Mammals can’t introduce C=C bonds beyond C9, so fatty acids such as linoleic acid must be obtained from the diet.

Question 11

What is the purpose of the carnitine shuttle in stage 2 of lipid metabolism?

Answer 11

It transports activated fatty acids (after linking to coenzyme A), across the inner membrane of the mitochondrion.
Fatty acyl CoA synthase, for the activation, requires ATP. The transport is regulated with acyl joining carnitine, crossing and then rejoining. As it’s CoA regulated, it controls the rate of fatty acid oxidation.

Question 12

What’s the activation of fatty acids inhibited by?

Answer 12

The biosynthetic intermediate malonyl-CoA.

Question 13

What are the consequences in defectsbin the transport system of activated fatty acids occur?

Answer 13

Exercise intolerance and lipid droplets in muscle.

Question 14

What happens once the activated fatty acids are inside the mitochondria?

Answer 14

Beta-oxidation removes C2 from the chain and reduces NAD+ and FAD. It uses water and repeats.

Question 15

What happens to the carbon lost in beta oxidation of triglycerides?

Answer 15

It may join CoA and then enter the TCA cycle.

Question 16

Fatty acid oxidation does not directly produce any ATP, so what is the point?

Answer 16

Produced reduced carrier molecules, which go on to contribute to oxidative phosphorylation. More energy is derived from fatty acid oxidation than that of glucose.

Question 17

Where/when does beta-oxidation of fatty acids occur?

Answer 17

In most tissues (not the brain, RBCs or WBCs), but it stops in the absence of oxygen.

Question 18

What happens to the glycerol drivered from triacylglycerol?

Answer 18

It is transported in the blood to the liver where it is metabolised. Glycerol kinase, uses a molecule of ATP to produce glycerol phosphate which can go on to triacylglycerol synthesis or reduce an NAD+ to produce DHAP, which can enter glycolysis.

Question 19

CoA contains vitamin B5 - panthenoic axid. What is the importance of acetyl-coenzyme A in metabolism?

Answer 19

It is the main convergent point for catabolic pathways and an important intermediate in catabolic and anabolic pathways.

Question 20

What are the 3 ketone bodies produced in the body?

Answer 20

1. Acetoacetate
2. Acetone (acetoacetate after spontaneous decarboxylation)
3. Beta-hydroxybutyrate

Question 21

What are the implications of different plasma ketone levels?

Answer 21

The normal plasma ketone level is <1mM. Physiological ketosis may occur during starvation, with a plasma ketone level of 2-10mM. Untreated diabetes (acts as a pseudo-starvation), can lead to plasma ketone levels > 10mM, meaning pathological ketosis.

Question 22

Ketones are synthesised in the mitochondria of hepatocytes from acetyl-CoA, first using synthase to produce what before which enzyme to produce the ketone bodies. What could be made from the intermediate instead and how is this avoided?

Answer 22

Synthase first produces HMG-CoA, which could go on to produce cholesterol, which can be avoided by the use of statin drugs to inhibit the enzyme HMG-CoA Reductase.

Question 23

How are ketone bodies made when there’s low NAD+ substrate availability or NADH product inhibition of TCA cycle enzymes, meaning oxaloacetate is not regenerated.

Answer 23

Acetyl-CoA cannot be derived from the TCA cycle to make ketone bodies.
… they’re not.

Question 24

In starvation or diabetes, insulin:glucagon ratio may be low, lyase will be activated and reductase inhibited, with what outcome?

Answer 24

Ketone body synthesis provides alternative, soluble fuel molecule (no need for blood carrier), so glucose can be used where it’s needed, such as the brain.

Question 25

When a person is fed, what’s the affect on acetyl-CoA?

Answer 25

Insulin means that it’s converted into HMG-CoA, which goes on to produce cholesterol, instead of ketone bodies.

Question 26

What happens when the level of ketone bodies in the blood is above renal threshold?

Answer 26

It is excreted in the urine = ketonuria. This is a test for diabetes.

Question 27

What may happen if the concentration of ketone bodies gets really high and why?

Answer 27

Acetoacetate and beta-hydroxybutyrate are strong organic acids, so large amount of them can lead to ketoacidosis.
Volatile acetone may be excreted via the lungs (nail varnish remover smell).