Lipid metabolism and pathways Flashcards

1
Q

Lipid function

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

TG

A

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

Metabolite = reactants, intermediates and products

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4
Q

Metabolite

A

reactants, intermediates and products

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5
Q

TG - digestion and absorption

A

TG emulsified by bile acids

TGs are hydrolysed by enzyme Pancreatic Triacylglycerol lipase

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6
Q

Pancreatic triacylglycerol lipase

A

Hydrolyse Gs

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7
Q

TG metabolism

A

Oxidation in mitochondria to release energy in ATP form

Synthesis of TG from acetyl-CoA

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8
Q

Oxidation of TGs

A

Oxidation of long chain fatty acids to 2C fragments (acetyl-CoA)

Oxidation of acetyl-CoA to CO2 in citric acid cycle

Transfer electrons from reduced electron carriers to mitochondrial respiratory chain

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9
Q

B-oxidation

A

Process releases free energy - successive removal of 2C fragments from fatty acids

Mitochondria and peroxisomes

Fatty acids activated by attachment to CoA (Cytosol)
Transfer Acyl-CoA across mitochondrial membrane (rate limiting)
Progressive oxidation of FA by removal of 2C units to form A-CoA

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10
Q

Each cycle (shorten by 2C) produces:

A

A-CoA
FADH2
NADH

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11
Q

Fatty acid synthesis

A

Occurs mostly in liver and adipocytes

Longer chain carbon molecules built from 2C

Occurs in cytosol (A-CoA in mitochondrial)

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12
Q

FA biosynthesis

A

Citrate -> Acetyl CoA -> Malonyl CoA

Both A-CoA and M-CoA bind to FA synthase
Condensation reaction adds to 2C - involves M-CoA

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13
Q

Rate limiting steps

B-oxidation
FA synthesis

A

B-oxidation: transfer A-CoA into mitochondria

FA synthesis: Form M-CoA from A-CoA (acetyl CoA carboxylase)

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14
Q

Activation of A-CoA carboxylase

A

Insulin favours dephosphorylation of A-CoA carboxylase

Complex control of gene expression of lipogenic enzymes

Excess dietary intake of some polyunsaturated fatty acids can repress the synthesis of these enzymes in the liver

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15
Q

Cholesterol

A

Amphipathic
Synthesised by A-CoA and eliminated as bile acids
Storage = cholesterol esters

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16
Q

Cholesterol role

A

Important lipid membrane component

Precursor of steroid hormones

Source of bile acids

17
Q

Bile acids role

A

Lipid digestion
Lipid absorption
Cholesterol excretion

18
Q

Statins

A

Competitive inhibitor of HMG-CoA reductase

Bulky - prevent binding with substrate

Lovastatin (Mevacor), Compactin, Pravastatin (pravachol), Simvastatin (Zocor).

Synthetic Statins: Atorvastatin (Lipitor), Fluvastatin (Lescol)

19
Q

Lovastatin

A

Natural

Mevacor

20
Q

Mevacor

A

Lovastatin

Natural

21
Q

Compactin

A

Natural

22
Q

Pravastatin

A

Pravachol

Natural

23
Q

Pravachol

A

Pravastatin

Natural

24
Q

Simvastatin

A

Zocor

Natural

25
Q

Zocor

A

Simvastatin

Natural

26
Q

Atorvastatin

A

Lipitor

Synthetic

27
Q

Fluvastatin

A

Lescol

Synthetic

28
Q

Transport of lipids around body

A

Dietary lipids to cells - 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 tissue to liver for excretion

29
Q

Transport lipids in blood

A

Short Chain FA transported bounded to blood proteins

Bulk transport (neutral lipids) insoluble in water, require special carrier proteins (lipoprotein)

Lipoproteins are composed of hydrophilic, hydrophobic and amphipathic molecules

30
Q

Lipid transport

A
  • Chylomicrons: deliver dietary TGs to muscle and adipose tissue + dietary cholesterol to the liver
    • VLDL: transport endogenous TGs and cholesterol
    • LDL: transport cholesterol from liver to tissues
    • HDL: transport cholesterol from tissues to liver i.e. remove cholesterol from tissues
31
Q

Tangier disease

A

Cells laden with cholesterol and few HDL are formed bc of mutation in ABCA1 enzyme - allows cholesterol efflux from cells

32
Q

ABCA1 enzyme

A

Allows cholesterol efflux from cells

33
Q

Lipid uptake in cells

A
  • Chylomicrons and VLDL particles give up lipid (TG) to tissues by the action of tissue-bound lipases
    • The liver recognises remnants of these particles by their ApoE content, and takes them up for re-cycling
    • LDL particles contain ApoB-100, which is recognised by cell surface LDL receptors
34
Q

ApoB-100

A

Recognised by cell surface LDL receptors

35
Q

Further regulation of cholesterol uptake - control LDL receptors

A

PCSK9 binds to LDL receptor and results in its degradation

PCSK9: Less LDL receptor on cell membranes and higher plasma LDL-C

36
Q

PCSK9

A

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

proprotein convertase subtilisin/kexin type 9

37
Q

Antibodies for PCSK9

A

Evolocumab (Repatha) and alirocumab (Praluent) are monoclonal antibodies that bind to PCSK9 - produce profound reduction in circulating LDL cholesterol