Lipid Metabolism Flashcards

1
Q

What are the uses of fat in the body?

A
  1. As an energy source.
  2. For essential fatty acids: some polyunsaturated fatty acids cannot be made in the body.
  3. For fat-soluble vitamins: A, D, E and K.
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2
Q

What can essential fatty acid deficiencies lead to?

A

Membrane disorders, increased skin permeability and mitochondrial damage.

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3
Q

What are the 3 main groups of lipids?

A

Simple (e.g. fatty acids, triglycerides, waxes).
Compound (associated with other groups e.g. phospholipids, glycolipids, lipoprotein).
Steroids (cholesterol, steroid hormones).

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4
Q

What is another name for triglycerides?

A

Triacylglycerols.

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5
Q

What is the main energy storage form in adipose tissue?

A

Triglycerides.

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6
Q

What does compact mean when talking about triglycerides?

A

They don’t require concomitant storage of water.

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7
Q

Do fatty acids normally contain an odd or even number of carbons?

A

Even.

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8
Q

What configuration are the double bonds normally in?

A

The cis configuration.

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9
Q

What are the main natural fatty acids and how many carbon atoms and bonds do they contain?

A

Palmitic acid: 16:0.
Stearic acid: 18:0.
Oleic acid: 18:1 (monounsaturated).

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10
Q

Can the body synthesise many polyunsaturated fatty acids?

A

No.

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11
Q

What are the 2 naming systems of fatty acids?

A

Either carboxyl group is C-1 or C adjacent to carboxyl carbon is alpha carbon e.g. C-2 and C furthest away is omega carbon.

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12
Q

Why are omega 3 fatty acids called that?

A

It has a double bond 3 carbons away from the last carbon in the chain (omega carbon).

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13
Q

What is the maximum number of carbons a fatty acid can have before it becomes a solid?

A

8.

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14
Q

What are the 3 main products of fat digestion?

A

Glycerol (readily absorbed in intestinal epithelial cells), fatty acids, monoglycerides.

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15
Q

What happens to short and medium length fatty acids absorbed into the intestine?

A

They enter portal blood.

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16
Q

What happens to longer length fatty acids and monoglycerides absorbed into the intestine?

A

They are re-synthesised into triglycerides (then coated with layer of protein, phospholipid and cholesterol to form chylomicrons which are transportable in the bloodstream).

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17
Q

What decides what will happen to the free fatty acids when they reach adipose tissue or skeletal muscle?

A

The amount available.

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18
Q

What enzymes breakdown triglycerides and when does this occur?

A

Hormone-sensitive lipases e.g. adrenaline-sensitive. Occurs when energy is needed.

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19
Q

In fatty acid oxidation, what is the first step?

A

Combining the fatty acid with CoA to form acyl-CoA (requires 2ATP).

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20
Q

Once formed, where does acyl-CoA need to be transported?

A

To the mitochondrial matrix.

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21
Q

What allows the transport of acyl-CoA across the mitochondrial membrane?

A

The carnitine shuttle.

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22
Q

Describe how the carnitine shuttle works.

A
  1. In cytoplasm, fatty acids are transferred from acyl-CoA to carnitine to form acyl carnitine.
  2. Acyl carnitine antiports with carnitine through antiporter in inner membrane.
  3. CoA inside matrix removes fatty acid from the carnitine to form acyl CoA in the mitochondrion.
  4. Carnitine transported out via the antiporter.
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23
Q

How many steps are there in beta-oxidation?

A

4 steps in each cycle.

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24
Q

What is produced after each cycle of beta-oxidation?

A

1 acetyl-CoA, 1 acyl-CoA (shortened by 2 carbons), 1 FADH2, 1 NADH + H+ (electron carriers).

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25
Q

Instead of an acetyl-CoA and an acyl-CoA, what is formed after the last cycle of beta-oxidation?

A

2 acetyl-CoAs.

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26
Q

What is the P/O ratio?

A

Amount of ATP gained per reduction of single oxygen atom to water.

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27
Q

How does beta-oxidation yield energy?

A

Acetyl-CoA can enter TCA cycle, electron carriers can enter oxidative phosphorlylation.

28
Q

What is the energy yield from a complete beta-oxidation of stearic acid?

A

120 ATP.

29
Q

What is the difference in beta-oxidation with unsaturated fatty acids?

A

They are already partially oxidised to yield less FADH2.

30
Q

What is the difference in beta-oxidation with odd-chain fatty acids?

A

They yield propionyl-CoA in last step (3 carbon atoms), converted to succinyl-CoA which enters TCA cycle directly.

31
Q

What is the difference in beta-oxidation with branched-chain fatty acids?

A

C-1 carbon oxidised to CO2, acetyl-CoA and propionyl-COA released in equal numbers.

32
Q

What are the downsides of these additional pathways of beta-oxidation?

A

They require several additional enzymes and less energy can be derived.

33
Q

What are the 2 steps in the breakdown of glycerol?

A
  1. Activated to glycerol-3-phosphate by glycerol kinase.

2. Dehydrogenated to dihydroxyacetone phosphate: normal intermediate of carbohydrate metabolism.

34
Q

Where is glycerol kinase located?

A

Liver and kidney, absent from adipose tissue, skeletal and heart muscle.

35
Q

How are ketone bodies formed and where?

A

In liver mitochondira from acetyl-CoA from beta-oxidation.

36
Q

What do ketone bodies contain?

A

Ketone groups.

37
Q

What are the 3 ketone bodies?

A

Acetoacetate, acetone and hydroxy-butyrate.

38
Q

Where are ketone bodies important molecules for energy metabolism and how?

A

Heart muscle and renal cortex. They are converted back to acetyl-CoA which enters TCA cycle.

39
Q

What is the overall function of ketone bodies?

A

They are an alternative way for the body to move energy around.

40
Q

Why are there high levels of ketone bodies in the blood during starvation or diabetes?

A

Oxaloacetate is consumed for gluconeogenesis. Oxidation of fatty acids produces lots of acetyl-CoA which cannot eneter TCA cylce due to lack of oxaloacetate. Acetyl-CoA is converted into ketone bodies leading to high levels in blood.

41
Q

Why does a large concentration of ketone bodies in the blood lead to severe acidosis?

A

They are moderate acids and accumulation means that blood can’t buffer anymore.

42
Q

What are the effects of ketoacidosis?

A

Impairs tissue function esp CNS (can lead to acidotic coma and death).

43
Q

What smell can be detected on the breath of someone with ketoacidosis?

A

Acetone.

44
Q

Where does lipogenesis occur?

A

Mainly liver, kidney, mammary glands, adipose tissue and brain.

45
Q

What happens when excess carbohydrate is taken in?

A

Conversion to fatty acids and triglycerides in the liver, free fatty acids are transported in plasma bound to albumin, triglycerides formed in the liver are transported to adipose tissue by VLDL for storage.

46
Q

Is lipogenesis oxidative or reductive.

A

Reductive (electrons are required).

47
Q

Give an overview of lipogenesis.

A

Dietary starch -> glucose -> pyruvate -> acetyl-CoA -> fatty acids -> triglycerides.

48
Q

Where does synthesis of fatty acids from acetyl-CoA occur and why does this require a new transport mechanism?

A

In the cytoplasm of liver cells. Acetyl-CoA is generated in mitochondrial matrix. Inner mitochondrial membrane is impermeable to acetyl-CoA.

49
Q

How is acetyl-CoA transported to the cytoplasm for lipogenesis?

A

Citrate transports acetyl groups into the cytoplasm: citrate is formed by combo of acetyl-CoA and oxaloacetate, when present in high concentrations is transported into the cytoplasm.

50
Q

What is the vital first step of lipogenesis?

A

Conversion of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase.

51
Q

What does acetyl-CoA carboxylase do?

A

Makes a 3 carbon malonyl group out of an acetyl group and a bicarbonate (requires 1 ATP).

52
Q

What is the function of malonyl-CoA?

A

It donates carbon atoms to the new lipid.

53
Q

Describe the structure of fatty acid synthase.

A

Consists of a dimer of identical polypeptides: single polypeptide chain with seven distinct enzyme activities.

54
Q

What part of fatty acid synthase carried the growing fatty acid chain?

A

Acyl-carrier protein (ACP).

55
Q

What are the precursors to the fatty acid synthase reaction?

A

Acetyl-CoA and malonyl-CoA.

56
Q

What happens with each cycle of reactions?

A

2 carbon atoms are added to the growing acyl chain (derived from malonyl-CoA).

57
Q

What is the growing acyl chain attached to?

A

ACP (acyl-carrier protein).

58
Q

What is the electron donor in lipogenesis?

A

NADPH.

59
Q

At what length of fatty acid is the fatty acid released and what is the longest fatty acid produced by fatty acid synthase?

A

C-16. Palmitic acid.

60
Q

What would be required to elongate the chain further or add unsaturated bonds?

A

Further enzymes.

61
Q

What is the enzyme that plays a key role in regulating fatty acid synthesis and degradation?

A

Acetyl-CoA carboxylase.

62
Q

How do hormones affect the activity of Acetyl-CoA carboxylase?

A

Insulin: stimulates storage of fuels and synthesis of proteins.
Glucagon: switches fatty acid synthesis off.
Adrenaline: mobilises glycogen stores.

63
Q

What can allosterically modify the action of acetyl-CoA carboxylase?

A

Citrate: stimulates as levels are high when acetyl-CoA and ATP are abundant.
Palmitoyl-CoA: antagnoises acetyl-CoA carboxylase as is abundant when fatty acids are in excess.

64
Q

What form of glycerol is required for synthesis of triglycerides?

A

Glycerol-3-phosphate (G3P).

65
Q

What does the liver and adipose tissue produce G3P from?

A

Liver: glycerol.

Adipose tissue: glucose.

66
Q

When does adipose tissue produce triglycerides?

A

During the fed state as insulin stimulates adipose tissue uptake of glucose.

67
Q

What other lipids does the liver make?

A

Phospholipids, cholesterol and lipoproteins.