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Medicine Year 2 > Endocrine Topic 7 - Lipid Metabolism > Flashcards

Endocrine Topic 7 - Lipid Metabolism Flashcards

1
Q

List the types of dietary lipids

A

Triglycerides
Cholesterol
Phospholipids

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2
Q

Describe the structure of triglycerides

A

Glycerol bound to three fatty acids by ester bonds, fatty acids can be saturated (no double bonds), monounsaturated (one double bond) or polyunsaturated (many double bonds)

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3
Q

Where does lipid digestion primarily occur?

A

In the small intestine

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4
Q

Which enzymes break down triglycerides? What is their clinical significance?

A

Pancreatic lipase and colipase break down TAG into 2 fatty acids and monoglyceride - targets of orlistats

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5
Q

What is the first stage in lipid metabolism?

A

Emulsification of large lipid droplets into small droplets by bile salts (emulsifiers)

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6
Q

How are lipids absorbed?

A
  1. Water soluble micelles of fatty acids and monoglycerides and absorbed into intestinal cells
  2. TAG reformed in intestinal cell
  3. TAG packaged with cholesterol, lipoproteins and other lipids to form chylomicrons
  4. Chylomicrons released into lymphatic system by exocytosis
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7
Q

How are fatty acids used once absorbed by adipose cells?

A

Storage as triglycerides, formation of structural phospholipids, oxidation to form ATP

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8
Q

What is the function of lipoprotein lipase?

A
  1. Hydrolyses triglycerides in lipoproteins (e.g. in chylomicros and VLDL) into two free fatty acids and one monoglyceride
  2. Promotes cellular uptake of chylomicron remnants, cholesterol-rich lipoproteins and free fatty acids
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9
Q

Where is lipoprotein lipase found?

A

On the luminal surface of endothelial cells in capillaries

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10
Q

Describe the transport of lipids in chylomicrons

A
  • Triglyceride component of chylomicrons is hydrolysed by lipoprotein lipase, allowing the released FFA to be absorbed by the tissues
  • When a large portion of the triacylglycerol core have been hydrolysed, chylomicron remnants are formed and taken up by the liver, transferring dietary fat to the liver
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11
Q

Describe the features of fat metabolism which alter plasma TAG (lipoproteins) and FFA (albumin-bound) concentration

A
  • Increased by fatty acid synthesis, dietary lipids and release of TAG from adipose tissue
  • Decreased by storage of TAG in adipose tissue, phospholipid synthesis, beta-oxidation and ketone body formation
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12
Q

What is the first step in beta-oxidation of fatty acids?

A

Fatty acids added to acetyl coA to form fatty acyl-coA

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13
Q

What is beta-oxidation?

A

Generation of energy from fatty acids

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14
Q

Where does beta-oxidation of fatty acids occur?

A
  • Within the mitochondrion - must cross the inner mitochondrial membrane
  • Requires carrier molecule - carnitine
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15
Q

From what is carnitine derived?

A

Derived from lysine and methionine

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16
Q

Where is carnitine found in high concentrations?

A

High in muscle

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17
Q

Describe the process of beta oxidation

A
  • Fatty acyl coA degraded by oxidation at the beta-carbon
  • Occurs in rounds reducing size of fatty acyl chain by 2 carbons each time
  • Produces 1 FADH2, NADH and acetyl coA (2 carbons) per turn
  • Ends up with final acetyl coA
18
Q

How does beta oxidation lead to ATP production?

A
  • Acetyl CoA can be further oxidised to yield ATP (TCA cycle/oxidative phosphorylation)
  • Fatty acids are an excellent source of ATP
19
Q

Describe triglyceride synthesis

A
  • Esterification of 3 fatty acids and glycerol
  • Diacylglycerol acyl transferase re-esterifies
  • Glycerol obtained from glycolysis
20
Q

Describe the regulation of hormone-sensitive lipase

A

Activated by cAMP-dependent phosphorylation in response to adrenaline in fasted state, inhibited by insulin

21
Q

How are fatty acids synthesised?

A
  • Fatty acids built 2 carbons at a time (limit is 16 carbons)
  • Key regulatory enzymes are acetyl coA carboxylase (forms malonyl coA) and fatty acid synthase
22
Q

What is the effect of malonyl coA?

A

Inhibits fatty acid oxidation

23
Q

Describe the process of fatty acid synthesis

A
  • Acetyl coA carboxylase forms malonyl coA
  • Acetyl coA couples to malonyl coA
  • 7 successive steps by multifunctional enzyme (fatty acid synthase) - active in tissues that make fatty acids
  • Requires NADPH from the pentose phosphate pathway
  • Occurs in the cytoplasm
24
Q

Why are ketone bodies formed?

A
  • Beta-oxidation leads to substantial amounts of acetyl coA production
  • Ketone body formation is an overflow pathway for acetyl coA use
  • If oxaloacetic acid is not present, acetyl coA does not go through TCA cycle and will by converted to ketones
25
Q

Give examples of ketone bodies

A

Acetoacetate, beta-hydroxybutyrate, acetone

26
Q

Describe ketone body formation

A

Acetyl coA + acetyl coA = acetoacetyl coA

Acetoacetyl coA - coA = acetoacetate

Acetoacetate can be converted to acetone and beta-hydroxybutyrate

27
Q

Describe formation of phospholipids

A

Same as first steps of triglyceride synthesis to form DAG, then combined with an alcohol
High levels of phospholipid synthesis in rapidly-dividing cells

28
Q

List different phospholipids

A 
Phosphatidylethanolamine
Phosphatidylglycerol
Phosphatidylserine
Phosphatidylinositol
Phosphatidylcholine
29
Q

What are essential fatty acids?

A

Cannot be synthesised, obtained from diet (originally vitamin F)
Polyunsaturated omega-3 or omega-6

30
Q

What is the function of essential fatty acids?

A

Cell membrane formation

Required for proper growth and development

Required for brain and nerve function

Precursors for eicosanoids - prostanoids and leukotrienes (inflammatory response)

31
Q

How are essential fatty acids related to cardiovascular disease?

A

Omega-3:
Protect vs heart and circulatory disease
Reduce plasma TAG
Not clear whether sources of omega3 fatty acids other than oily fish provide the same benefits

Omega-6:
May lower LDL
High intakes may also lower HDL

32
Q

What are the key hormones which regulate lipid metabolism?

A

Key regulation by insulin and (nor)adrenaline

33
Q

What is the effect of insulin in lipid metabolism?

A

Stimulates fatty acid and TAG synthesis

Suppresses lipolysis

34
Q

What is the effect of (nor)adrenaline in lipid metabolism?

A

Stimulates lipolysis

35
Q

How does insulin influence lipid metabolism?

A

Stimulates:
GLUT4-mediated transport of glucose
Acetyl coA carboxylase activity
Increases expression of fatty acid synthase
Increases activity of lipoprotein lipase (in adipose)

36
Q

How does (nor)adrenaline influence lipid metabolism?

A

Stimulates:
cAMP synthesis
cAMP-dependent protein kinase (PKA) activation
PKA-mediated phosphorylation and activation of hormone sensitive lipase

37
Q

How does insulin inhibit lipolysis?

A

Insulin stimulate breakdown of cAMP, therefore (nor)adrenaline is no longer able to stimulate lipolysis

38
Q

Describe the regulation of lipoprotein lipase in a fed state

A

Increased LPL synthesis and activity in adipocytes

Decreased LPL synthesis and activity in skeletal and heart muscle

39
Q

Describe the regulation of lipoprotein lipase in a fasted/exercise state

A

Decreased LPL synthesis and activity in adipocytes

Increased LPL synthesis and activity in muscle

40
Q

What are the potential effects of elevated fatty acids?

A

Lipotoxicity:
Lipolysis overactive/adipose tissue storage for TAG exceeded
FA taken up and stored as TG in liver, muscle
Metabolites of FA impair insulin signalling
Impaired insulin action in liver, muscle adipose - increased lipolysis and gluconeogenesis, decreased glucose uptake and glycogen synthesis
Impaired insulin secretion by beta-cell
= HYPERGLYCAEMIA

Medicine Year 2 (41 decks)

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