lipid metabolism and pathways

Question 1

what are the biological functions of lipids? 4

Answer 1

• 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)

Question 2

what are triglycerides? 4

Answer 2

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

Question 3

describe the metabolism of triglycerides? 3

Answer 3

• 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)

Question 4

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

Answer 4

• 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

Question 5

explain beta oxidation of fatty acids? 4

Answer 5

• 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

Question 6

explain fatty acid synthesis? 4

Answer 6

• 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!

Question 7

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

Answer 7

• 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

Question 8

explain fatty acid biosynthesis? 3

Answer 8

• 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

Question 9

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

Answer 9

• 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)

Question 10

describe cholesterol? 3

Answer 10

• 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

Question 11

what are the physiological roles of cholesterol? 3

Answer 11

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

Question 12

what are bile acids? 4

Answer 12

• polar derivatives of cholesterol
• aid in lipid digestion
• aid in lipid absorption
• aid in cholesterol excretion

Question 13

what is the structure of cholesterol?

Answer 13

• 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)

Question 14

what is the basic order for cholesterol synthesis? 5

Answer 14

• acetyl CoA
• HMG-CoA + HMG-CoA reductase
• mevalonate
• squalene
• cholesterol

Question 15

what is the rate defining step for cholesterol synthesis? 5

Answer 15

• 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

Question 16

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

Answer 16

• 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

Question 17

how are lipids transported in the blood? 3

Answer 17

• 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

Question 18

give a summary of lipid transport? 4

Answer 18

• 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

Question 19

explain lipid uptake by cells? 3

Answer 19

• 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