lipid metabolism & pathways

Question 1

what are the biological functions of lipids?

Answer 1

• essential components of cell membranes
• inter and intra cellular signalling events
• energy generation and fuel storage
• metabolism

Question 2

what are the 2 metabolic pathways of triglycerides?

Answer 2

1) TGs broken into free fatty acids and glycerol. oxidation of fatty acids in the mitochondria to release energy in the form of ATP
2) synthesis of fatty acids from acetyl-CoA (joined to a glycerol molecule for storage)

Question 3

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

Answer 3

1) removal of glycerol and oxidation of long chain fatty acids to 2-carbon fragments in the form of acetyl-CoA which is BETA OXIDATION
2) oxidation of acetyl-CoA to CO2 in the citric acid cycle
3) transfer of electrons from reduced electron carriers to mitochondrial respiratory chain

Question 4

what are the steps of beta oxidation within the mitochondria and peroxisomes?

Answer 4

1) fatty acids activated by attachment to coenzyme A (in the cytosol)
2) transfer of acetyl-groups across mitochondrial membrane (rate limiting step)
3) progressive oxidation of fatty acids by removal of 2-carbon units to form acetyl-CoA which enters the citric acid cycle

Question 5

where does fatty acid synthesis occur?

Answer 5

• mainly in the liver and adipocytes
• occurs in the cytosol
• acetyl CoS is in the mitochondria

Question 6

give the overview of fatty acid biosynthesis

Answer 6

citrate —> acetyl CoA —> 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 7

what is the rate limiting step for beta oxidation?

Answer 7

transfer of acyl-CoA into mitochondria

Question 8

what is the rate limiting step for fatty acid synthesis?

Answer 8

formation of malonyl CoA from acetyl-CoA, catalysed by acetyl CoA carboxylase (subject to control by glucagon and insulin)

Question 9

what are the physiological roles of cholesterol?

Answer 9

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

Question 10

what are bile acids?

Answer 10

polar derivatives of cholesterol

Question 11

what do bile acids aid in?

Answer 11

• lipid digestion
• lipid absorption
• cholesterol excretion

Question 12

what is the structure of cholesterol?

Answer 12

• amphipathic lipid (hydrophobic and hydrophilic regions)
• synthesised from acetyl CoA and eliminated as bile acids
• storage form is cholesterol esters found in most tissues
• cholesterol acyltransferase catalysed formation of cholesterol esters

Question 13

where are the major sites of cholesterol biosynthesis?

Answer 13

• liver

- lesser amounts made in intestine and adrenal cortex

Question 14

what are the general steps of cholesterol biosynthesis?

Answer 14

acetyl CoA —> HMG-CoA —> mevalonate —> squalene —> cholesterol

Question 15

why do we transport lipids around the body?

Answer 15

• 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 diet to cells for synthesising cell membranes
• carry cholesterol from peripheral tissues to the liver for excretion

Question 16

how are lipids transported in the blood?

Answer 16

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

Question 17

in what type of lipids are the levels of free cholesterol and cholesterol esters the highest?

Answer 17

LDL (low density lipoproteins)

Question 18

what does VLDL, IDL, LDL and HDL stand for?

Answer 18

VLDL = very low density lipoproteins
IDL = intermediate density lipoproteins
LDL = low density lipoproteins
HDL = high density lipoproteins

Question 19

what do chylomicrons transport?

Answer 19

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

Question 20

what do VLDLs transport?

Answer 20

transport endogenous TGs and cholesterol

Question 21

what do LDLs transport?

Answer 21

transport cholesterol from liver to tissues

Question 22

what do HDLs transport?

Answer 22

transport cholesterol from tissues to liver (reverse cholesterol transport)

Question 23

what are the 2 major steps in the digestion of dietary TGs?

Answer 23

1) TGs need to be emulsified by bile acids

2) TGs are then hydrolysed by the enzyme pancreatic triacylglycerol lipase

Question 24

how are lipids uptaken by cells?

Answer 24

• chylomicrons and VLDL particles give up lipid 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

Question 25

how does cellular cholesterol homeostasis work?

Answer 25

• when cellular cholesterol levels are low, a conformation change occurs allowing SREBPs to be transported out of the ER to the Golgi apparatus for activation
• SREBPs can then transcriptionally regulate several steroid response element genes in lung HMG-CoA reductase and LDL receptors
• therefore the response to low cholesterol levels is to increase both cholesterol synthesis and uptake of cholesterol from the plasma