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Module 103: The Heart, Lungs and Blood > Theme 3: Lecture 15 - Lipid metabolism and pathways > Flashcards

Theme 3: Lecture 15 - Lipid metabolism and pathways Flashcards

1
Q

What are the biological functions of lipids

A
  • Essential components of cell membranes e.g. phospholipids, glycolipids, cholesterol
  • Inter- and intra-cellular signalling events e.g. precursor of steroid hormones
  • Energy generation and fuel storage i.e. triglycerides
  • Metabolism e.g. bile acids
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2
Q

Describe triacylglycerols

A
  • Constitute c. 90% of dietary lipids
  • Major form of metabolic energy storage in humans
  • Hydrophobic
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3
Q

What are the 2 major metabolic pathways for TG metabolism

A
  • Synthesis of fatty acids from acetyl-CoA (joined to a glycerol molecule for storage)
  • TGs broken into free fatty acids and glycerol. Oxidation of fatty acids in the mitochondria to release energy in the form of ATP
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4
Q

What are the 3 stages to achieve complete oxidation of fatty acids to CO2 and H2O

A
  • Removal of glycerol and oxidation of long chain fatty acids to 2-carbon fragments in the form of acetyl-CoA: THIS IS β-OXIDATION
  • Oxidation of acetyl-CoA to CO2 in the citric acid cycle
  • Transfer of electrons from reduced electron carriers to mitochondrial respiratory chain
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5
Q

What are the 3 steps of beta oxidation

A

1st step: fatty acids activated by attachment to Coenzyme A (CYTOSOL)
2nd step: transfer of acyl-groups across mitochondrial membrane
3rd step: progressive oxidation of fatty acids by removal of 2-carbon units at a time to form acetyl-CoA which enters the citric acid cycle

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6
Q

What is the rate limiting step of beta oxidation

A

Step 2 - transfer of acyl groups across mitochondrial membrane

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7
Q

What is formed through each cycle of beta oxidation which shortens the fatty acid chain by 2C

A
  • 1 acetyl-CoA
  • 1 FADH2
  • 1NADH
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8
Q

How are acyl groups transferred across the mitochondrial membrane

A
  • The acyl group dissociates from CoA on the cytosol side of the mitochondrial membrane
  • Carnitine palmitoyl transferase I catalyses binding of the acyl group to Carnitine
  • Carnitine carrier protein transfers the acyl group bound to carnitine across the membrane
  • The acyl group dissociates from carnitine and recombines with another CoA on the mitochondrial side of the membrane catalysed by carnitine palmitoyl transferase II
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9
Q

Where does fatty acid synthesis occur

A

Mainly in the liver and adipocytes

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10
Q

Where does fatty acid synthesis occur

A

in the cytosol

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11
Q

How does acetyl CoA get out of the mitochondria to be used in fatty acid synthesis

A

Due to the citrate malate cycle

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12
Q

What is the rate limiting step of fatty acid synthesis

A

Formation of malonyl CoA from acetyl CoA, catalysed by acetyl CoA carboxylase

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13
Q

Describe fatty acid synthesis

A

-Citrate is converted into Acetyl CoA which is converted into Malonyl CoA
The conversion of acetyl CoA to Malonyl CoA is catalysed by acetyl CoA carboxylase
-Malonyl CoA and acetyl CoA both bind to fatty acid synthase
-A series of condensation reactions involving malonyl CoA adds further C2 units

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14
Q

Describe the citrate malate cycle

A
  • Acetyl CoA combines with oxaloacetate in the mitochondria to make citrate
  • This is catalysed by citrate synthase
  • Citrate is transported out of the mitochondria into the cytosol via the tricarboxylate transporter
  • Citrate is converted back into oxaloacetate and acetyl CoA
  • This is catalysed by citrate lyase
  • Oxaloacetate is converted into malate
  • Malate is converted into pyruvate
  • Pyruvate is transported back into the mitochondria via the pyruvate transporter where it can reform oxaloacetate and acetyl CoA
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15
Q

What is cholesterol’s relationship with water

A

it is amphipathic

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16
Q

What is cholesterol synthesised from

A

Acetyl CoA

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17
Q

What is cholesterol eliminated as

A

Bile salts

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18
Q

Which enzymes catalyse formation of cholesterol esters

A

Cholesterol acyltransferases

19
Q

What are the roles of cholesterol

A
  • Important lipid component of biological membranes
  • Precursor of steroid hormones
  • Source of bile acids
20
Q

What are bile acids

A

Bile acids are polar derivatives of cholesterol

21
Q

What are the roles of bile acids

A
  • lipid digestion
  • lipid absorption
  • cholesterol excretion
22
Q

Describe cholesterol synthesis

A
  • Acetyl CoA is converted into HMG-CoA
  • HMG-CoA is converted into mevalonate which is catalysed by HMG-CoA reductase
  • Mevalonate is converted into squalene
  • Squalene is converted into cholesterol
23
Q

What is the target site for statins

A

HMG-CoA reductase

24
Q

What is the rate determining step of cholesterol biosynthesis

A

Conversion of HMG-CoA into mevalonate

25
Q

What are feedback inhibitors for conversion of HMG-CoA to mevalonate

A

cholesterol and mevalonate

26
Q

Why do lipids need to be transported around the body

A
  • Bring dietary lipids to cells for energy production or storage
  • Move lipids from storage in adipose tissue for use in energy production
  • Provide lipids from the diet to cells for synthesizing cell membranes
  • Carry cholesterol from peripheral tissues to the liver for excretion
27
Q

How are short chain fatty acids transported in the blood

A

bound to blood proteins like albumin

28
Q

How are the bulk of neural lipids which are insoluble in water transported in the blood

A

Via lipoproteins

29
Q

Describe the structure of lipoproteins

A
  • Lipoproteins are composed of hydrophobic, hydrophilic and amphipathic molecules
  • Lipids are carried in the central core
  • The outer layer of amphipathic phospholipids contains cholesterol and apolipoproteins
30
Q

All classes of lipoproteins contain apolipoprotein E apart from

A

LDL

31
Q

What apolipoprotein does LDL contain

A

B-100

32
Q

Which lipoprotein carries the greatest amount of protein

A

LDL

33
Q

Where do chylomicrons transport lipids

A

deliver dietary TGs to muscle and adipose tissue + dietary cholesterol to the liver

34
Q

Where does VLDL transport lipids

A

transport endogenous TGs and cholesterol

35
Q

Where does LDL transports lipids

A

Transport cholesterol from liver to tissues

36
Q

Where does HDL transport lipids

A

Transport cholesterol from tissues to liver i.e. remove cholesterol from tissues (reverse cholesterol transport)

37
Q

What are the major steps in digestion of dietary TGs

A
  • TGs need to be first emulsified by bile acids

- TGs are then hydrolysed by the enzyme pancreatic triacylglycerol lipase

38
Q

What enzyme allows release of TG at tissues

A

Lipoprotein lipase

39
Q

Chylomicrons and VLDL particles give up lipid (TG) to tissues by the action of what

A

tissue bound lipases

40
Q

How does the liver recognise remnants of chylomicron and VLDL particles

A

By their apolipoprotein E content

41
Q

What does the liver do to remnants of chylomicron and VLDL particles

A

Takes them up for recycling

42
Q

How are LDL particles that contain apolipoprotein B-100 recognised by cells

A

By cell surface LDL receptors (LDLRs)

43
Q

Describe how LDL receptors are regulated

A

-Expression of LDL receptors increased
by SREBPs in response to low cholesterol. SREBPs are transcription factors
-The LDL receptor is then recycled back into the membrane
-PCSK9 binds to LDL receptor and results in it’s degradation so the LDL receptor is not recycled back into the membrane
-This reduces the amount of cholesterol taken into the cell meaning that there in more in the blood
-PCSK9 = proprotein convertase subtilisin/kexin type 9

44
Q

What does uptake of cholesterol into the cell result in

A

Decrease in cholesterol and LDL receptor synthesis

Module 103: The Heart, Lungs and Blood (51 decks)

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