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1 - Metabolism > Lipids and lipid metabolism > Flashcards

Lipids and lipid metabolism Flashcards

1
Q

Why are lipids carried in association with proteins?

A

Because they’re insoluble in plasma

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2
Q

What are the two ways in which lipids are carried in blood, and in what proportions does this occur

A

~98% carried as highly specialised non-covalent assemblies called lipoprotein particles~2% mostly fatty acids are carried bound non-covalently to albumin.

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3
Q

What is the significance of albumin bound fatty acids?

A

fatty acids released from adipose tissue during lipolysis and are used as a fuel by tissues

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4
Q

Why can only a limited amount of fatty acids be carried on albumin?

A

Albumin has limited capacity for fatty acids, therefore blood fatty acid levels do not normally exceed ~3mM.

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5
Q

What two diseases do disorders of lipoprotein metabolsim have significance in?

A

atherosclerosis and coronary artery disease.

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6
Q

Give five types of lipid

A

Cholesterol (transports fatty acids)Cholesterol EsterPhospholipidsTriacylglycerolFatty Acids

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7
Q

Give four functions of cholesterol

A

Major component of membranesPrecursor of steroid hormonesPrecursor of bile acidsCan be esterified with a fatty acid, which elminates the only polar part.

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8
Q

Where does cholesterol come from? What is it synthesised from? What enzyme is used?

A

Some from diet, but mostly synthesied in liverHydroxymethylglutaric acid, a product of acetyl CoA catabolism via “synthase” enzyme. Reductase enzyme helps convert hmga to cholesterol.

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9
Q

Give three features of phospholipids

A

Diacylglycerl with phosphate groupMajor component of membranesPhosphate is polar

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10
Q

How do lipoproteins differ?

A

in the lipid being transported, the origins of the lipid and its destination

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11
Q

What are the protein components of a lipoprotein known as?

A

apoproteins

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12
Q

What is the structural role of apoproteins in lipoproteins? What two features allow them to fulfill this role?

A

apoproteins are involved in packaging non-water soluble lipids into soluble form. This is possible as they contain hydrophobic regions that interact with lipid molecules and hydrophilic regions that interact with water.

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13
Q

What is the functional role of apoproteins?

A

activation of enzymes or the recognition of cell surface receptors.

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14
Q

What does apoprotein composition determine?

A

Function of a lipoprotein particle

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15
Q

What is the macrostructure of a lipoprotein?

A

Spherical particles that consist of a surface coat (shell) and a hydrophobic core.

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16
Q

What does the surface coat of a lipoprotein contain?

A

phospholipids, cholesterol and apoproteins

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17
Q

What does the hydrophobic core of a lipoprotein contain?

A

Triacylglycerol and cholesterol esters

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18
Q

What must occur when core lipids are removed, and why?

A

the surface coat must be reduced, as lipoproteins are only stable if they maintain their spherical shape

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19
Q

What is the difference between core and surface components in terms of transferability?

A

Many components of the surface coat are free to transfer. The core components can only be removed by special proteins e.g. lipases and transfer proteins.

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20
Q

Give the transport function of chylomicrons. How long are they present after a meal?

A

Transport dietary triacylglycerols from the intestine to tissues such as adipose tissue. Normally only present in blood 4-6 hours after meal (see below)

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21
Q

Give the transport function of VLDL’s

A

Transport of triacylglycerols synthesised in the liver to adipose tissue for storage. Combine TAGs synthesised in liver with specific apoproteins.

22
Q

Give the transport function of LDLs

A

Transport of cholesterol synthesised in the liver to tissues. Combine synthesised cholesterol in liver with specific apoproeins.

23
Q

Give the transport function of HDL

A

Transport of excess tissue cholesterol to the liver for disposal as bile salts.

24
Q

What does higher levels of LDLs signify?

A

Higher risk of atherosclerosis

25
Q

What does a low HDL/LDL ratio lead to?

A

Cardiovascular disease

26
Q

Why are TAGs transported in Chylomicrons?

A

Because they cannot be absorbed directly

27
Q

Give the digestive path of TAGs and their consituents

A

TAGs hydrolysed in SI by pancreatic lipase, which releases fatty acids and glycerolFatty acids enter epithelial cells of SI where they’re re-esterified to TAGs using glycerol phosphate from glucose metabolism.The TAGs are then packaged with other dietary lipids into chylomicrons.

28
Q

How are chylomicrons released from epithelial tissues into blood stream?

A

The lymphatic system

29
Q

What tissues are chylomicrons transported to?

A

Tissues such as adipose tissue which express extracellular enzyme lipoprotein lipase.

30
Q

What does extracellular lipoprotein lipase do, and where is it located?

A

Attached to inner surface capillaries of tissues such as adipose and muscle. Hydrolyses TAGs in lipoproteins, releasing fatty acids and glycerol. Then takes up fatty acids and glycerols go to liver.

31
Q

What does LCAT do?

A

Restores stability of lipoproteins by coverting surface lipid to core lipid. Converts of cholesterol to cholesterol ester using fatty acid lethicin.

32
Q

What does deficiency of LCAT do?

A

Results in unstable lipoproteins of abnormal structure, so failure of lipid transport. Lipid deposits occur in many tissues, causing atherosclerosis.

33
Q

What three things are produced from VLDL metabolism?

A

1.Glycerol – remains in circulation2.Fatty acids – enter tissues for metabolsim 3.VLDL remnants - Usually removed by liver or converted to other types of lipoprotein particles

34
Q

What process is used in LDL metabolism?

A

receptor-medicated endocytosis. LDL particles are taken up by the cell and the cholesterol released inside the cell.

35
Q

What two ways can cells receive cholesterol?

A

able to synthesise cholesterol from acetyl~CoAuptake of pre-formed cholesterol circulating in plasma lipoproteins.

36
Q

How do cells uptake preformed cholesterol?

A

Cells requiring cholesterol synthesise LDL receptors that are exposed on the cell surface.These receptors recognise and bind to specific apoproteins (Apo B100) on the surface of the LDL. The LDL receptor with its bound LDL is then endocytosed by the cell and subjected to lysosomal digestion.Cholesterol esters are converted to free cholesterol that is released within the cell.

37
Q

What happens to cholesterol once inside a cell?

A

The cholesterol can be stored (as cholesterol esters) or used by the cell

38
Q

What is hyperlipoproteinaemias?

A

Raised levels of one or more lipoprotein classes

39
Q

What three things can Hyperlipoproteinaemias be caused by?

A

defectiveEnzymesReceptorsApoproteins

40
Q

Describe type 1 Presentation Disease linksCause

A

Chylomicrons in fasting plasmaNo link to coronary artery diseaseCaused by defective lipoprotein lipase

41
Q

Describe type IIa (familial hypercholesterolamia) Presentation Disease linksCause

A

Raised LDLAssociated with coronary artery disease that may be severeCaused by defective LDL receptor

42
Q

Describe type IIbPresentation Disease linksCause

A

Raised LDL and VLDLAssociated with coronary artery diseaseDefect unknown

43
Q

Describe type III Presentation Disease linksCause

A

Raised IDL and chylomicrons remnantsAssociated with coronary artery diseaseCaused by defective apoprotein (Apo. E)

44
Q

Type IV
Presentation Disease links Cause
Type V
Presentation Disease links Cause

A

Raised VLDL
Associated with coronary artery disease
Defect unknown

Raised chylomicrons and VLDL in fasting plasma
Associated with coronary artery disease
Defect unknown

45
Q

Give six steps of atheroma formation

A

Oxidised LDL –> Macrophages –> Foam cells –> accumulate in intima of blood vessel walls –> Fatty streak → Atheroma

46
Q

What is familial hypercholesterolaemia? What is caused by? What is it characterised by? What happens to homozygotes and heterozygotes?

A

Type IIa hyperlipoproteinaemia)A condition in which there may be an absence (homozygous) or deficiency (heterozygous) of functional LDL receptors.Characterised by elevated levels of LDL and cholesterol in the plasmaHomozygotes develop extensive atherosclerosis early in life and heterozygotes develop the condition later in life.

47
Q

What are three symptoms of hyperchoesterolaemia?

A

Xanthelasma – Cholesterol deposits in eyelidsTendon Xanthoma – Cholesterol deposits in tendonsCorneal arcus – Cholesterold deposits in cornea

48
Q

How can you treat hyperlipoproteinaemias?

A

Diet and lifestyle modifications
- Aim to reduce cholesterol and TAG in diet.
Drug therapy
- Statins, Bile sequesterants
Drug therapy - Statins lower plasma cholesterol by reducing synthesis of cholesterol in tissue. Also increase expression of LDL receptors in hepatocytes.

49
Q

What is the biological mechanism of statins? Why are there side effects?

A

Statins inhibit production of other intermediates in the HMG-CoA reductase metabolic pathway, which may account for side effects. Addition of Co-enzyme Q-10 to diet my alleviate some side effects however.

50
Q

How does liver dispose of cholesterol?

A

by converting it into bile salts and secreting a small amount directly in the bile.

51
Q

How do bile salt sequestarants lower plasma cholesterol?

A

by binding to bile salts in the GI tract preventing them from being reabsorbed into the hepatic-portal circulation and promoting their loss in the faeces.

1 - Metabolism (17 decks)

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