Metabolism S5 - Lipid Transport and Byproducts of Energy Metabolism Flashcards Preview

ESA1 Callum's cards > Metabolism S5 - Lipid Transport and Byproducts of Energy Metabolism > Flashcards

Flashcards in Metabolism S5 - Lipid Transport and Byproducts of Energy Metabolism Deck (59):
1

How are lipids transported in the blood?`

98% via lipoprotein particles

2% bound to albumin

2

What are the albumin bound fatty acids in the blood used for and where do they come from?

Used as fuel by tissues

Fatty acids released from adipose tissue during lipolysis and bind to albumin in blood

3

What is the maximum normal level of Fatty acids in the blood and why is it limited to this value?

~3mM

Limited carrying capacity of albumin

4

Why are plasma lipoproteins significant to medicine?

Disorders in their metabolism are associated with important diseases such as athersclerosis and coronary artery disease

5

What is the term for the protein components of a lipoprotein?

Apoproteins

6

What are the functions of apoproteins?

Packaging lipids into water soluble form

Activation of enzymes

Recognition of cell surface receptors

7

Why are Apoproteins well suited to lipid packaging in plasma?

Have hydrophobic regions that interact with lipids and hydrophilic regions that interact with water

8

Describe the general structure of Lipoproteins

Spherical particles with a surface coat and hydrophobic core

9

What might a surface coat of a lipoprotein contain?

Phospholipids

Cholesterol

Apoproteins

10

What might a lipoprotein core contain?

Cholesterol esters

TAGs

11

What is a lipoprotein's stability dependent on?

Lipoproteins only stable if they maintain their spherical shape, this is dependent on the ratio of core to surface lipids

12

Explain how removal of lipids from core or coat is performed

In core, when lipids removed other lipids from coat must be removed to maintain stability of lipoprotein.

Many components of coat are free to transfer however some must be removed by special proteins (eg. Lipase or transfer proteins).

13

What are the 4 major types of lipoprotein?

Chylomicrons

VLDL

LDL

HDL

14

What is the basic function of Chylomicrons?

Transport of dietary TAGs from intestine to tissues such as adipose tissue

15

Where are chlyomicrons produced?

Epithelia of small intestine

16

How are chylomicrons transported? From where to where?

Chylomicrons released from small intestine epithelia into lymphatic vessels that drain into the bloodstream.

The bloodstream then transports them to adipose tissues

17

In the small intestine epithelia what are TAGs packaged with in chylomicrons?

Other dietary lipids such as cholesterol and ADEK vitamins

18

How are TAGs in chylomicrons converted to fatty acids and glycerol in adipose tissue?

Adipocytes express extracellular lipoprotein lipase which hydrolyses TAGs to release fatty acids into the adipose cells

19

What processes must occur to produce TAGs in the small intestine epithelia from TAGs in the intestine's lumen?

Pancreatic lipase hydrolyses TAGs to release glycerol and FAs which are absorbed by epithelia whereupon they are re-esterified using glycerol phosphate

20

What is the transport function of VLDL?

Transport of TAGs synthesised in the liver to adipose tissues for storage

21

What is the transport function of LDLs?

Transport of cholesterol synthesised by the liver to adipose tissues for storage

22

What is the transport function of HDL?

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

23

What is the function of lipoprotein lipase?

Hydrolysis of TAGs in lipoprotein (such as chylomicrons or VLDLs) core releasing fatty acids and glycerol

24

Where do the products of lipoprotein lipase go after hydrolysis?

TAGs absorbed by adipose tissue

Glycerol transported to liver for storage

25

Where is lipoprotein lipase found?

Lining capillaries inner surface in tissues such as adipose or muscle

26

What is the function of Lecithin: Cholesterol acyltransferase (LCAT)

How does it carry out this function?

Restores stability of lipoproteins by converting cholesterol to cholesterol esters using fatty acid derived from lecithin (surface to core, restoring ratio)

27

What is the result of a lecithin: cholesterol acyltransferase deficiency?

What is one serious medical issue that can result?

 

Unstable lipoproteins of abnormal structure therefore general failure of lipid transport and excess lipid deposits in tissues are made

Excess lipid deposits can cause athersclerosis

28

How do tissues obtain cholesterol?

From LDLs

29

How are LDLs in the bloodstream taken up by tissues and then released?

Receptor mediated endocytosis

LDL particles taken into the cell and cholesterol is released inside the cell.

30

Where can cholesterol synthesis occur?

All tissues except erythrocytes

31

What is cholesterol synthesised from?

Acetyl-CoA

32

How do cells prefer to satisfy their cholesterol needs?

Uptake of preformed cholesterol from lipoproteins produced in the liver as opposed to making their own (which almost all tissues can do).

33

Explain in detail the process of binding, absorption and use of LDLs and contents by tissues.

Cells requiring cholesterol synthesis LDL receptors that are exposed on the cell surface

Receptors bind to specific apoprotein on LDL surface (Apo B100)

LDL is endocytosed and subjected to lysosymal digestion which converts cholesterol esters in LDL core to cholesterol

Cholesterol is either used or stored in ester form by the cell

Cholesterol inhibits LDL receptor synthesis preventing the cell accumulating too much cholesterol.

34

What is the cause and consequences of Type 1 hyerlipoproteinaemia?

Is it associated with Coronary artery disease?

Caused by defective lipoprotein lipase

Causes chylomicrons in fasting plasma

Not associated with CAD

35

What is the cause and consequence of type 2a hyperlipoproteinaemia?

Is it linked to coronary artery disease?

Caused by defective LDL receptor

Causes raised LDL in plasma

Associated with CAD that may be severe

36

What is the cause and consequence of type 2b hyperlipoproteinaemia?

Is it linked to coronary artery disease?

Defect unknown

Causes raised LDL and VLDL

Associated with CAD

37

What is the cause and consequences of type 3 hyperlipoproteinaemia?

Is it linked to coronary artery disease?

Caused by defective apoprotein (Apo. E)

Causes raised IDL (intermediateDL) and chylomicron remnants

Associated with CAD

38

What is the cause and consequence of type 4 hyperlipoproteinaemia?

Is it linked to coronary artery disease?

Defect unknown

Raised VLDL

Associated with CAD

39

What is the cause and consequence of type 5 hyperlipoproteinaemia?

Is it linked to coronary artery disease?

Defect unknown

Causes raised chylomicrons and VLDL in fasting plasma

Associated with CAD

40

What is familial hypercholesterolaemia, what structures does it affect, what are the different forms and how does it affect the sufferer?

Another name for type 2a hyperlipoproteinaemia

Characterised by lack of LDL receptors causing raised LDL and cholesterol in plasma

Homozygotes lack LDL receptors altogether, develop athersclerosis early in life

Heterozygotes are LDL receptor deficient and develop athersclerosis later in life

41

What are the two methods of treating hyperlipoproteinaemia?

Diet/lifestyle modification

Drug control

42

Describe diet/lifestyle control of hypolipoproteinaemia

Aims to reduce TAGs (especially those with saturated fatty acids) and cholesterol in diet

Will have little effect in some patients

43

What 2 classes of drugs are used for control of hyperlipoproteinaemia?

Give examples and explain their method of action.

Statins (eg Simvastin)

Work by reducing cholesterol synthesis in tissues

Bile Acid Sequestrants (eg. Cholestyramine)

Prevent reabsorption of bile salts secreted by the liver into the intestine.

As bile salts are produced from cholesterol this is effectively increasing cholesterol excretion

44

How are superoxide radicals produced?

Leakage of electrons (0.1-2%) from transport complexes 1/3 prematurely reduce oxygen forming O2- free radicals

45

What is another name for superoxide radicals and similar extremely reactive species?

Reactive oxygen species (ROS)

46

What is the effect of ROS in the cells?

Damages DNA, proteins and the cell membrane

47

What is the first step in neutralising superoxide radicals? Give the enzyme responsible

Explain why the products of this reaction are not ideal

Superoxide dismutase (SOD) catalyses reaction of superoxides into hydrogen peroxide and oxygen

H2O2 is also an ROS

48

What reactions are used to break down hydrogen peroxide?

Catalase enzyme breaks H2O2 down into H2O and O2

The Fenton reaction can use Fe(2+) ions to produce hydroxyl radicals from H2O2

49

Describe Hydroxyl radicals

Hint: What do they do? Why are they dangerous?

Highly reactive ROS that damage cells

Particularly damaging to membranes

Cannot be eliminated via enzymatic reaction

50

What cells are capable of oxidative burst?

Monocytes and Neutrophils

51

Describe an oxidative burst

Hint: What is released? what enzyme is involved? What is the result?

Rapid release of ROS from a cell

Utilises NADPH oxidase

Cell is usually destroyed, but so are surrounding bacterial or fungal cells

52

How are oxidising agents produced if not via enzymatic or electron transport based reaction?

Can be produced via ionising radiation (UV light, X rays, Gamma rays)

Certain chemicals also produce oxidising agents

E.g. Primaquine and paraquat

53

How is Nitric oxide produced and what would we consider nitric oxide to be?

Nitric oxide is a free radical

Produced from arginine via inducible enzyme nitric oxide synthase

54

How is peroxynitrite produced and what process is it involved in?

Nitric oxide and oxygen react to for peroxynitirite

Involved in inflammation

55

What are some other methods of cellular defence against ROS apart from SOD and Catalase enzymes?

NADPH and Glutathione

Antioxidant vitamins

Flavenoids

Minerals

56

How are NADPH and Glutathione (GSH) involved in cellular protection from ROS?

GSH is a tripeptide that can donate the Hydrogen from a -SH on its cysteine residue to act as a reducing agent

The oxidised form of GSH is Gluthathione disulphate (GSSG) that can be oxidised by NADPH to regenerate GSH

57

What enzymes are involved in Glutathione and Glutathione disulphide interconversion?

Glutathione peroxidase (GSH to GSSG)

Glutathione reductase (GSSG to GSH)

58

Give 4 examples of how oxidative stress is involved in diseased states

Involved in cancer - ROS damage DNA

Involved in Diabetes Mellitus type 1 - ROS destroy beta cells

Involved in Pancreatitis - ROS damage tissues

Cardiovascular Disease - ROS cause Lipid oxidation, forming lipid peroxides, the damage caused to cell membranes thought to be involved in early stages of CV diseases.

59