Lipid transport an function Flashcards

1
Q

What does a triglyceride contain?

A

Glycerol and 3 fatty acid chains

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2
Q

What does it mean when a fatty acid is saturated?

A

No double bond

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3
Q

Why do we need lipids?

A

Lipids are good for you
-Energy and energy store
-Vitamins antioxidants (transport)
-Insulation
-Protects organs
-Structure (brain)
-Phospholipids - bilayer cell membrane integrity
-Hormones prostaglandins
-Gene expression
-Essential fatty acids (hormones and cell membrane)

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4
Q

How is fat absorbed into the body?

A

1) Droplet
2) Bile emulsifies in the intestine into smaller droplets *increase in SA is good for enzyme activity
3) Monoglycerides and pre fatty acids formed
4) These enter the epithelial of the small intestine as micelles
5) Triglyceride again
6) Aggregate into protein

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5
Q

What is the name of lipids and cholesterol which are transported into the blood as complexes of lipids and proteins?

A

Lipoproteins

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6
Q

What part of a lipoprotein is hydrophobic?

A

Core with triglycerides

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7
Q

What part of the lipoprotein is hydrophilic and why?

A

Coating - to help facilitate in cell uptake. Cholesterol/Polar phospholipids

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8
Q

What are the FIVE classes of lipoproteins?

A

-Chylomicrons
-Very low density lipoproteins (VLDL)
-Low density lipoproteins (LDL)
-Intermediate density lipoproteins (IDL)
-High density lipoproteins (HDL)

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9
Q

What does HDL do?

A

‘GOOD’
Reverse cholesterol transport, takes free cholesterol to the liver to prevent build up of plaques

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10
Q

What does LDL do?

A

‘BAD’
Tries to deposit in cells and tissues and then drops into arteries and a plaque is formed (atherosclerosis) = stroke / mi

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11
Q

What is ApoB100?

A

Apolipoprotein
-In VLDL, IDL, LDL, main physiological ligand for LDL receptor and made in the liver.
LDL - which interacts with the LDL receptors, and is highly expressed in the liver, peripheral and is uptaken into cells

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12
Q

What is HDL like?

A

More dense, has a higher amount of protein

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13
Q

What is the pathway for exogenous lipids?

A

1) Cholesterol and TG from the diet are absorbed in the ileum, transports in the chylomicrons to the lymph, blood then capillaries to the muscle and adipose tissue.
2) TG is hydrolysed by lipoprotein lipase, glycerol and free fatty acids are released which are taken up into tissues
3) Remaining chylomicrons remnants with cholesteryl esters travel to the liver, bind to receptors and are endocytosed
4) Cholesterol is stored, oxidised to bile acids or enters the endogenous pathway

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14
Q

What is the pathway for endogenous lipids?

A

1) Cholesterol from diet and newly made TG in liver travels as VLDL to muscle and adipose tissue
2) TG is hydrolysed in tissues by lipoprotein lipase, then glycerol and FFA is liberated
3) Lipoprotein partciles become smaller but retain cholesterol esters and become LDL, which binds to LDL receptors on cells - (LDL receptors recognise apopB100 on LDL particles)
4) Cholesterol deposited in tissues for cell membranes and other functions
5) Cholesterol can return to plasma and liver for tissues via HDL (reverse cholesterol transport) - Plasma -> Liver -> excretion
6) Cholesterol is esterified with LCFA in HDL and transferred to VLDL or LDL in plasma by cholesteryl ester transfer protein (CETP)

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15
Q

What is the LDL receptor pathway?

A

1) LDL attached to the liver
2) pH is less than 5, –> LDL dissociates from the receptor
3) Vescile pinches apart = 2 vesciles
1= LDL which fuses with lysozyme - cholesterol release in cytosol - cell membrane formation
2= receptors, recycle to cell surface –>fuses to cell membrane, –> turns inside out (exocytosis) –> return cell surface process begins again!

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16
Q

How does the reverse cholesterol transport system work?

A

HDL is made in the liver and small intestine,
1) Taken up and esterfies
2) HDL more spherical
3) Transfer to liver cells
4) Excretion

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17
Q

What is the role of ACAT-acyl CoA.

A

Cholesterol acyltransferase
-Catalyses intracellular synthesis of cholesterol ester in macrophages, adrenal cortex, gut and liver

18
Q

What is a potent ACAT inhibitor?

A

Tamoxifen

19
Q

What is the function of LCAT?

A

Lecithin cholesterol acyltransferase
-Catalyses cholesteryl ester synthesis in HDL particles

20
Q

What is the function of CETP?

A

Cholesteryl ester transfer protein
-Transfer of cholesteryl ester between HDL to IDL or VLDL

21
Q

What is the function of PLTP?

A

Phospholipid transfer protein
-Transfer of cholesterol and TG between different classes of lipoprotein particles in plasma
-CETP inhibition is a potential therapeutic strategy

22
Q

What is dyslipidaemia?

A

A disorder of lipid metabolism including lipoprotein overproduction and deficiency

23
Q

What causes dyslipidaemia?

A

-Increased total cholesterol (TC)
-Increased low density lipoprotein (LDL)
-Increased triglyceride (TG)
-Decreased high density lipoprotein (HDL)

24
Q

What are the stages of Atherosclerosis?

A

1) Epithelial cell injury from smoking, DM, or HTN
2) Adhesion molecules bind to epithelial cells
-monocytes and oxygenated LDL form foam cells and then stick to blood vessels and cause plaque formation and an inflammatory response occurs
3) This causes a fibrotic cap, which is thin and can rupture exposing the necrotic core in the plaque
4) This is what causes a MI or Stroke

25
Q

What is classed as an ok cholesterol?

A

Below 5

26
Q

What would the cholesterol level have to be, to consider using a lipid lowering agent?

A

6+

27
Q

What happens to LDL within the blood vessels?

A

It is oxidised - forming plaque and then leading to atherosclerosis

28
Q

What is the target LDL?

A

Below 3

29
Q

What causes Primary Dyslipidaemia?

A

*Diet and genetics
*5 Inherited conditions
*Diet and lifestyle

30
Q

What diet and lifestyle factors can contribute to having primary dyslipidaemia?

A

-High saturated fat diet
-Physically inactive
-Overweight or obese
-Smoking
-Large waist circumference

31
Q

What causes Secondary Dyslipidaemia?

A

There is an underlying cause!!
-Disease or certain drugs such as, diabetes, liver disease, thiazides, GC
-Natural rise as age and after menopause

32
Q

What are the 5 genetic conditions that can cause primary dyslipidaemia?

A

1)Familial hypercholesterolaeia
Mutations in LDLR or APOB or PCSK9
-Homozygous >20mmol/L
-Heterozygous -8 mmol/L
2) Familiar combined hyperlipidaemia / Type 3 hyperlipidaemia
3) Polygenic hypercholesterolaemia
4) Primary hypertriglyceridaemia
5) Lysosomal acid lipase deficiency

33
Q

What is a sign of Familiar combined hyperlipidaemia?

A

Fasting TG >1.5mmol/L
-Can happen at age 20-30

34
Q

What mutation do you have in Type 3 hyperlipidaemia?

A

ApoE

35
Q

What is there a deficiency in, in primary hypertriglyceridemia?

A

Lipoprotein lipase deficiency

36
Q

What happens when someone has lysosomal acid lipase deficiency?

A

Breaks down fat in lysosomes normally but instead fat builds up in cells

37
Q

Where may you see signs of hyperlipidaemia?

A

-Corneal arcus (eyes)
-On top of eye lids (Xanthelesma)
-Elbows (tendon xanthomas)

38
Q

How can liver damage cause secondary dyslipidaemia?

A

Can’t transport or excrete the excess

39
Q

What underlying disorders can cause secondary dyslipidaemia?

A

Diabetes, Hypothyroidism, Chronic renal failure, Alcoholism, Liver disease

40
Q

Why is Lipoprotein A a risk factor?

A

It is strongly associated with atherosclerosis, it is localised in the atherosclerosis lesions.
Apo(a) is structurally similar to plasminogen.
Lp(a) inhibits binding of plasminogen to receptors on endothelial cells and this leads to less plasmin generation and promotion of thrombosis.

41
Q

How does Apo(a) cause coagulation?

A

A clot is formed, and the clot breaks down by plasminogen, Lp(a) inhibits, meaning clots can’t be broken down.

42
Q

What are non-pharmacological treatment of dyslipidaemia?

A

Dietary modification
-Low saturated fat, low trans fat, high mono or polyunsaturated fat - to decrease LDL and increase HDL
-Oily fish twice a week
-Plant sterols and stanols to decrease cholesterol absorption from gut
-High fibre - soluble fibre (from fruit and veg) may decrease cholesterol absorption from gut
Normal measures - smoking, weight-loss, reduce alcohol, exercise