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103: Theme 3 > Lipid metabolism > Flashcards

Lipid metabolism Flashcards

1
Q

Biological functions of lipids

A

Essential components of cell membranes

Energy generation and storage

Inter and intra-cellular signalling events

Metabolism

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2
Q

Triacylglyverols

A

Consider 90% of dietary lipids

Major form of metabolic energy storage in humans

Hydrophobic in nature

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3
Q

Metabolic pathways

A

Series of connected enzymatic reactions that produce specific products

Reactants, intermediates and products are known as ‘metabolites’

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4
Q

Triacylglycerols: digestion and absorption

A

TGs need to first be emulsified by bile acids

TGs then hydrolysed by pancreatic triacylglycerol lipase

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5
Q

Products of lipid digestion

A

Mixture of fatty acids and mono and diacylglycerols

Can be absorbed by intestinal mucosa

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6
Q

TG metabolism

A

2 major metabolic pathways:

  • oxidation in the mitochondria to release energy in the form of ATP
  • synthesis of TG from acetyl-CoA (for storage)
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7
Q

Oxidation of TGs

A

3 stages oxidation of fatty acids to CO2 and H2O:

  1. Oxidation of long chain fatty acids to 2-carbon fragments in the form of acetyl-CoA: beta oxidation
  2. Oxidation of acetyl-CoA to CO2 in the citric acid cycle
  3. Transfer of electrons from reduced electron carriers to mitochondrial respiratory chain
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8
Q

Beta oxidation

A

Successive removal of 2-carbon fragments from fatty acid

Occurs in mitochondria and peroxisomes

  1. fatty acids activated by attachment to CoA (cytosol)
  2. transfer of acyl-CoA across mitochondrial membrane (rate-limiting step)
  3. progressive oxidation of fatty acids by removal of 2-carbon units to form acetyl-CoA which enters the citric acid cycle

2 pools of CoA as it does not cross the inner membrane

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9
Q

Fatty acid synthesis

A

Occurs mainly in liver and adipocytes

Long carbon chain molecules built up from 2-carbon units derived from acetyl CoA

Occurs in the cytosol

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10
Q

Overview of fatty acid biosynthesis

A

Citrate-> acetyl coA -> malonyl CoA

Malonyl CoA and acetyl CoA both bind to fatty acid synthase

Series of condensation reactions involving amnolyl CoA adds further C2 units

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11
Q

Control of fatty acid oxidation and synthesis

A

Rate limiting steps:

  • beta oxidation: transfer of acyl-CoA into mitochondria
  • fatty acid synthesis: formation of malonyl CoA from acetyl-CoA, catalysed by acetyl CoA carboxylase
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12
Q

Cholesterol

A

Amphipathic lipid- OH

Synthesised from acetyl CoA and eliminated as bile acids

Storage form is cholesterol ester found in most tissues

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13
Q

Physiological roles of cholesterol

A

Important lipid component of biological membranes

Precursor of steroid hormones

Source of bile acids

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14
Q

Bile acids are polar derivatives of cholesterol and aid in

A

Lipid digestion

Lipid absorption

Cholesterol excretion

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15
Q

Cholesterol deposition in arteries

A

Associated with heart disease and stroke

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16
Q

Stage 1 of cholesterol biosynthesis

A

Acetyl CoA ->

HMG-CoA -> (NADPH- NADP+)(HMG-CoA reductase)

Mevalonate

17
Q

Stage 2 of cholesterol synthesis

A

Mevalonate -> (3ATP-3ADP)( CO2)

Active isporenoids -> (NADPH- NADP+)

Squalene (C30)

18
Q

Step 3 of cholesterol synthesis

A

Squalene (C30) -> (O2)(NADPH- NADP+) (squalene epoxidase/ cyclas)

Lanosterol (C30) (4-ring structure)

19
Q

Stage 4 of cholesterol synthesis

A

Lanosterol (C30)-> (O2) (NADPH -NADP+) (3CH3)

Cholesterol (C27)

20
Q

Cholesterol biosynthesis

A

Major sites: liver and intestine

Acetyl CoA ->
HMG-CoA -> (HMG reductase)
Mevalonate ->
Squalene ->
Cholesterol
21
Q

Statins

A

Competitive inhibitors of HMG-CoA reductase

Prevents enzyme from binding with HMG-CoA

Two classes:

  • natural statins
  • synthetic statins
22
Q

Natural statins

A

Lovastatin (mevacor)

Compactin

Pravastatin (pravachol)

Simvastatin (zocor)

23
Q

Synthetic statins

A

Atorvastatin (lipitor)

Fluvastatin (lescol)

24
Q

Transport of lipids around the body

A

Bring dietary lipids to cells for energy production or storage

Provide lipids from diet to cells for synthesising cell membranes

Move lipids from storage in adipose tissue for use in energy production

Carry cholesterol from peripheral tissues to liver for excretion

25
Q

Transport of lipids in the blood

A

Short chain fatty acids transported bound to blood proteins like albumin

Bulk transport of neutral lipids, which are insoluble in water, requires special carrier proteins: lipoproteins

26
Q

Lipoproteins

A

Composed of hydrophilic, hydrophobic and amphipathic molecules

27
Q

Structure of lipoproteins

A

Outer layer of amphipathic phospholipids contains cholesterol and has apoliporoteins associated with it

Lipids carried in central core

28
Q

Classes of lipoproteins

A

Chylomicrons (dietary TGL transport)

VLDL (endogenous TGL transport)

LDL (cholesterol transport)

HDL (reverse sterol transport)

29
Q

Chylomicrons

A

Deliver dietary TGs to muscle and adipose tissue and dietary cholesterol to the liver

30
Q

VLDL

A

Transport endogenous TGs and cholesterol

31
Q

LDL

A

Transport cholesterol from liver to tissues

32
Q

HDL

A

Transport cholesterol from tissues to liver i.e. remove cholesterol from tissues

33
Q

Lipid uptake by cells

A

Chylomicrons and VLDL particles give up TG to tissues by the action of tissue bound lipases

Liver recognises remnants of these partiles by ApoE content, takes them up for recycling

LDL particles contain ApoB-100 which is recognised by cell surface LDL receptors

34
Q

PCSK9

A

Binds to LDL receptor and results in its degradation

35
Q

Effects of PCSK9

A

Less LDL receptor on cell membranes and higher plasma LDL-C

103: Theme 3 (17 decks)

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