lipid metabolism and pathways Flashcards

1
Q

what are the biological functions of lipids? 4

A
  • essential components of cell membranes (phospholipids, glycolipids, cholesterol)
  • intra and inter cellular signalling events (precursor or steroid hormones)
  • energy generation and fuel storage (triglycerides)
  • metabolism (bile acids)
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2
Q

what are triglycerides? 4

A
  • storage lipid
  • constitute 90% of dietary lipids
  • major form of metabolic energy storage in humans
  • hydrophobic in nature
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3
Q

describe the metabolism of triglycerides? 3

A
  • depending on metabolic requirements there are 2 major metabolic pathways
  • TGs broken into free fatty acids and glycerol. oxidation of fatty acids in the mitochondria to release energy in the form of ATP
  • synthesis of fatty acids from acetyl-CoA (joined to a glycerol molecule for storage)
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4
Q

what are the 3 stages to achieve complete oxidation of fatty acids?

A
  • removal of glycerol and oxidation of long fatty acids to 2 carbon fragments in the for of acetyl-CoA. this is beta oxidation (oxidation of a carbon atom at a particular position relative to the carboxyl group
  • oxidation of acetyl-CoA in the citric acid cycle
  • transfer of electrons from reduced electron carries to the mitochondrial respiratory chain
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5
Q

explain beta oxidation of fatty acids? 4

A
  • occurs in mitochondria and peroxisomes
  • 1st step- fatty acids activated to CoenzymeA (cytosol)
  • 2nd step- transfer of acyl groups across the mitochondrial membrane (rate limiting step)
  • 3rd step- progressive oxidation of fatty acids by removal of 3-carbon units to form acetyl-CoA, which enters the citric acid cycle
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6
Q

explain fatty acid synthesis? 4

A
  • occurs mainly in liver and adipocytes
  • long carbon chain molecule built up from 2-carbon units derived from acetyl-CoA
  • occurs in the cytosol
  • but acetyl CoA is in the mitochondria!
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7
Q

how do we get Acetyl-CoA out of the mitochondria? 2

A
  • the tricarboxylate transporter takes citrate out of the mitochondria.
  • citrate lyase then makes ATP convert to ADP and CoA convert ti Acetyl CoA and this converts citrate to OAA
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8
Q

explain fatty acid biosynthesis? 3

A
  • citrate–> ACetyl-CoA (carboxylation= rate limiting)–> malonyl CoA
  • 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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9
Q

what are the rate limiting control steps of fatty acid oxidation and synthesis? 2

A
  • beta oxidation= transfer of acyl-CoA into mitochondria
  • fatty acid synthesis= formation of malonyl CoA from acetyl CoA, catalysed by acetyl CoA carboxylase (subject to control by glucagon and insulin)
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10
Q

describe cholesterol? 3

A
  • essential to life
  • deposition in arteries is associated with heart disease and stroke
  • in healthy organisms, balance is maintained between biosynthesis, utilisation and transport keeps harmful deposition to a minimum
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11
Q

what are the physiological roles of cholesterol? 3

A
  • important lipid component of biological membranes
  • precursor of steroid hormones
  • source of bile acids
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12
Q

what are bile acids? 4

A
  • polar derivatives of cholesterol
  • aid in lipid digestion
  • aid in lipid absorption
  • aid in cholesterol excretion
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13
Q

what is the structure of cholesterol?

A
  • amphipathic lipid (hydrophobic and hydrophilic portions) the OH does this
  • synthesised from acetyl-CoA and eliminated as bile acids
  • storage form is cholesterol ester found in most tissues (formation is catalysed by cholesterol acyltransferases)
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14
Q

what is the basic order for cholesterol synthesis? 5

A
  • acetyl CoA
  • HMG-CoA + HMG-CoA reductase
  • mevalonate
  • squalene
  • cholesterol
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15
Q

what is the rate defining step for cholesterol synthesis? 5

A
  • HMG-CoA+ HMG-CoA reductase
  • cholesterol is feedback inhibitor
  • mevalonate is feedback inhibitor
  • target site for statin drugs
  • reductase activity is regulated by insulin/glucagon
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16
Q

why do we need to transport lipids around the body? 4

A
  • bring dietary lipids to cells for energy production
  • move lipids from storage in adipose tissue for use in energy production
  • provide lipids from the diet to cells for synthesising cell membrane
  • carry cholesterol from peripheral tissue to the liver for excretion
17
Q

how are lipids transported in the blood? 3

A
  • short chain fatty acids are transported bound to blood proteins like albumin
  • bulk transport of neutral lipids which are insoluble in water, requires special carrier proteins- lipoproteins
  • neutral lipids carried in a central core with an outer layer of amphipathic phospholipids and cholesterol
18
Q

give a summary of lipid transport? 4

A
  • chylomicrons: deliver dietary Tgs to muscle and adipose tissue and dietary cholesterol to the liver
  • VLDL: transport endogenous TGs and cholesterol
  • LDL: transport cholesterol from liver to tissues
  • HDL: transport cholesterol from tissue to liver= reverse cholesterol transport
19
Q

explain lipid uptake by cells? 3

A
  • chylomicrons and VLDL particles give up liquid (TG) to tissue by the action of tissue-bound lipases
  • the liver recognises remnants of these particles by their ApoE content and takes them up for recycling
  • LDL particles contain ApoB-100 which is recognised by cell surface LDL receptors