Lipid Metabolism Flashcards

1
Q

List the lipids found in the diet and what they are used for in the body?

A

Triglycerides: Main lipid.
Cholesterol: For membranes and steroid hormone production. Cannot get energy from cholesterol.
Phospholipid: For membranes.

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2
Q

What kinds of fatty acids are found in triglycerides?

A
Saturated
Monounsaturated (C-C double bond). 
Polyunsaturated (multiple (C-C double bond). 

C-C double bond causes a kink. Loser structure e.g. oils.

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3
Q

What attaches fatty acids to the glycerol molecule in triglycerides?

A

Ester bonds.

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4
Q

Where does lipid digestion occur?

Via what enzymes?

A

Small intestine.

Pancreatic lipase and co-lipase: Break down TAG into 2 FA’s and MAG.
Bile Salts are also required to emulsify fats to micelles (tiny fat droplets to increase surface enzymes for enzymes to act).

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5
Q

How are lipids absorbed into cells?

A

TAG is broken down to MAG + 2FA’s.
They are transported into cells and then repackaged as triglyceride with cholesterol, lipoproteins and other lipids to form chylomicrons.
Chylomicrons enter lymphatic system via exocytosis.

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6
Q

Why must FFA’s be packaged as triglyceride or transported with albumin?

A

As they act as detergents and can break down cell walls.

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7
Q

How are lipids released from chylomicrons?

A

Adipose tissue ‘rips off’ triglyceride from the chylomicron using cell surface made from lipoprotein lipase.

This is upregulated in the fed state.

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8
Q

How does adipose use Fatty Acids?

A

Storage as TAG.
Structural (phospholipid).
Beta Oxidation for ATP.

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9
Q

What is Beta Oxidation?

Where does it occur?

A

Generates energy from fatty acids.
Fatty acids are added to CoA to give fatty acyl-CoA.
FACoA is degraded by oxidation at the Beta-carbon. Occurs by reducing the fatty acyl chain by 2 carbons each time.
It yeilds FADH2, NADH and acetyl CoA.
Aceytl CoA can be further oxidised in the TCA cycle to yeild ATP.

Occurs in the mitochondria, but must cross the inner mitochondrial membrane. This requires carrier molecule carnitine (high in muscle).

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10
Q

How are Fatty acyl CoA and Carnitine transported across the mitochondrial membranes?

A

By Carnitine Palmitoyl Transferase.
CPT 1 is on the outer membrane and CPT 2 is on the inner.

It swaps carnitine and FACoA for CoA and FAcarnitine, and back again in the inner membrane.
FACoA can then be used for B-Oxidation.

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11
Q

How is triglyceride synthesised?

Draw diagram of the cell.

A

Esterification of 3 Fa’s and glycerol.
Lipoprotein Lipase (LPL) hydrolyses TAG in chylomicrons/VLDL.
Diacylglycerol Acyl Transferase (DGAT) re-esterifies to TAG.

The glycerol is formed from glycolysis.

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12
Q

How is triglycerol broken down (lipolysis)?

A

TAG is broken down to glycerol and 3 FA’s by Hormone Sensitive Lipase (HSL) in adipose cells.
HSL is activated by cAMP-dependant phosphorylation in response to adrenaline in the fasted state. It is inhibited by insulin.

Liberated glycerol goes to the liver.
Liberated FA goes to muscle.

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13
Q

How are Fatty acids synthesised?

A

Built 2 carbons at a time until 16 carbons.
Regulatory enzymes are Acetyl CoA Carboxylase: Forms Malonyl CoA.
Fatty acid Synthase.
Requires NADPH (from pentose phosphate pathway).
Occurs in cytoplasm.
Uses the vitamin biotin from gut flora.

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14
Q

How are plasma TAG’s (lipoproteins) and FFA (albumin-bound) made?

A

Dietry lipids.
Fatty acid synthesis.
TAG conversion from adipose.

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15
Q

What are plasma TAG’s (lipoproteins) and FFA (albumin-bound) used fro?

A

Ketone bodies.
Beta-oxidation.
Phospholipid synthesis.

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16
Q

How are ketones formed?

A

B-oxidation makes lots of acetyl-CoA.
Ketone body formation is an ‘overflow’ pathway for acetyl CoA.

If oxaloacetate not present, acetyl CoA wont go through TCA cycle, but will be converted to ketones.

17
Q

List 3 ketone bodies?

A

Acetoacetate.
Beta-hydroxybutyrate.
Acetone.

18
Q

How are phospholipids synthesised?

A

Same as first steps of TAG synthesis to form DAG, then dombined with an alcohol.

19
Q

What has high levels of phospholipid synthesis?

A

Rapidly-dividing cells for making membranes.

20
Q

How are essential fatty acids made?

A

Cannot be synthesised so are obtained from diet.

Polyunsaturated omega-3 or omega 6.

21
Q

What are the functions of essential fatty acids?

A

Cell membrane formation.
Required for growth and development.
Brain and nerve function.
Precursors for inflammatory molecules - eicosanoids, prostanoids and leukotrienes.

22
Q

How can essential fatty acids prevent CV disease?

A

Reduce plasma TAG (omega-3).

May lower LDL and HDL (omega-6).

23
Q

How is lipid metabolism regulated?

A

Insulin;

  • Stimulates FA synthesis and TAG synthesis and supresses lipolysis.
  • Stimulates Glut 4 ediated transport of glucose
  • Stimulates ACC activity
  • Increases expression of FAS
  • Increses LPL activity in adipose.

(Nor)adrenaline: Stimulates lipolysis;

  • stimulates cAMP synthesis.
  • stimulates cAMP-dependent protein kinase (PKA) activation.
  • PKA-mediated phosphorylation and activation of HSL.
24
Q

How does insulin inhibit lipolysis?

A

Stimulates breakdown of cAMP, so (nor)adrenaline cant stimulate lipolysis.

25
Q

Describe regulation of lipoprotein lipase in the fed state?

A

Increased LPL synthesis and activity in adipocytes.

Decreased LPL synthesis and activity in skeletal and heart muscle.

26
Q

Describe regulation of lipoprotein lipase in the fasted and exercise state?

A

Decreased LPL synthesis and activity in adipocytes.

Increase LPL synthesis and activity in muscle.

27
Q

Describe the potential effect of elevated FA (lipotoxicity).

A

Lipolysis is overactive/adipose tissue storage capacity for TAG exceeded.
FA is taken up and stored as TG in liver and muscle.
Metabolites of FA impair insulin signalling.
Impaired insulin action in the liver, muscle and adipose.
This causes an increase in lipolysis and gluconeogenesis.
It also causes decreased glucose uptake and glycogen synthesis.
Causes impaired insulin secretion by the Beta-cell.
Results in hyperglycaemia.