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Metabolism, Endocrinology and Haematology > Session 2 - Energy Storage & Lipid Transport > Flashcards

Session 2 - Energy Storage & Lipid Transport Flashcards

1
Q

What are the 3 types of energy storage in humans?

A

Triacylglycerols
Glycogen
Muscle protein

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2
Q

When a person is obese, where is the additional energy stored in?

A

Triacylglycerols

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3
Q

What is gluconeogenesis?

A

Synthesis of glucose

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4
Q

What are the 2 types of bonds linking glucose residues together to form glycogen?

A

alpha1-4 and alpha1-6

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5
Q

What is the difference between alpha1-6 and alpha1-4 bonds?

A

Alpha1-6 bonds are branch points while alpha1-4 bonds join chains

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6
Q

Where and how is glycogen stored?

A

Stored in granules in liver and skeletal muscle

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7
Q

What are the 4 steps of glycogenesis?

A

Glucose to glucose 6 P
Glucose 6 P to glucose 1 P
Glucose 1 P to UDP glucose
Glycogen + UDP glucose to glycogen+1

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8
Q

What are the 4 enzymes involved in glycogenesis?

A

Hexokinase
Phosphoglucomutase
Glycogen synthase
Branching enzyme

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9
Q

What is the function of glycogen synthase?

A

Links glucose residues in series to glycogen primer by alpha1-4 bonds

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10
Q

What is the function of branching enzymes?

A

Links a glucose residue by alpha1-6 bond introducing a branch point

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11
Q

What is glycogenolysis?

A

Glycogen degradation

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12
Q

What are the 3 steps of glycogen degradation or glycogenolysis?

A

Glycogen to glucose 1 P
Glucose 1 P to glucose 6 P
Glucose 6 P to glycolysis (skeletal) OR to glucose (liver)

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13
Q

What are the 4 enzymes involved in glycogenolysis?

A

Glycogen phosphorylase
Debranching enzyme
Phosphoglucomutase
Glucose 6 phosphatase (liver)

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14
Q

What are the 2 enzymes regulating synthesis and degradation of glycogen?

A

Glycogen synthase

Glycogen phosphorylase

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15
Q

What does insulin do to regulate synthesis and degradation of glycogen?

A

Insulin de-phosphorylates enzymes - hormone of plenty, so it will increase glycogen synthesis, activating glycogen synthase and decrease glycogen degradation, inhibiting glycogen phosphorylase

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16
Q

What does glucagon do to regulate synthesis and degradation of glycogen?

A

Glucagon phosphorylates, it is opposite of insulin so it will increase glycogen degradation, activating glycogen phosphorylase and decrease glycogen synthesis, inhibiting glycogen synthase

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17
Q

Where does gluconeogenesis occur?

A

Liver

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18
Q

What causes glycogen storage diseases?

A

Deficiency or dysfunction of enzymes of glycogen metabolism

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19
Q

What are 2 examples of glycogen storage diseases?

A

glucose 6 phosphatase deficiency - von Gierke’s disease

muscle glycogen phosphorylase deficiency - McArdle disease

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20
Q

What are the 3 major precursors of gluconeogenesis?

A

Lactate
Glycerol
Amino acids (mainly alanine)

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21
Q

Why can’t acetyl-coA be converted to glucose?

A

It cannot be converted to pyruvate bc PDH reaction is irreversible with the release of CO2

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22
Q

What are the 3 main enzymes involved in gluconeogenesis?

A

Phosphoenolpyruvate carboxykinase PEPCK (oxaloacetate to phospheonolpyruvate)
Fructose 1,6-bisphosphatase
Glucose-6-phosphatase

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23
Q

What are the 2 key enzymes involved in gluconeogenesis that are regulated by hormones?

A

Fructose 1,6-bispnosphatase

PEPCK

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24
Q

What is the effect of insulin on gluconeogenesis and how is it achieved?

A

Insulin is hormone of plenty, so inhibits gluconeogenesis, decreases amount of PEPCK and decreases amount and activity of fructose 1,6-phosphatase

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25
Q

What is the effect of glucagon on gluconeogenesis and how is it achieved?

A

Stimulates gluconeogenesis, increases amount of PEPCK and increases amount and activity of Fructose 1,6-bisphosphatase

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26
Q

What is the time course of glucose utilization from after feeding?

A

Glucose from food 2h after feeding
Glycogenolysis from glycogen up to 8-10h after feeding
Gluconeogenesis using lactate, glycerol and amino acids 8-10h onwards

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27
Q

Where is dietary triacylglycerol metabolized before being used or stored?

A 
Small intestine (TAG to fatty acid + glycerol) 
Intestinal epithelial cell - TAG to chylomicron
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28
Q

What is the effect of excess glycogen storage?

A

Tissue damage

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29
Q

What is the effect of diminished glycogen stores?

A

Hypoglycaemia and poor exercise tolerance

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30
Q

What is the function of glycogen in liver?

A

Buffer of blood glucose levels

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31
Q

What is the function of glycogen in muscle?

A

Enters glycolysis for energy production

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32
Q

Where is triacylglycerols stored?

A

Adipose tissue

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33
Q

Why is triacylglycerols an efficient energy store?

A

Energy content per gram is twice that of carbohydrates or proteins

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34
Q

What happens to triacylglycerols when they are metabolized before being stored or used?

A

Using pancreatic lipase in small intestine, TAG becomes fatty acids and glycerol, travels across intestinal epithelial cells and becomes chylomicrons which travels in lymph through thoracic duct, to blood through left subclavian vein

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35
Q

What are the 5 steps in lipogenesis?

A

Glucose to pyruvate through glycolysis in cytoplasm
Pyruvate enters mitochondria and forms acetyl-coA and oxaloacetate which condense to citrate
Citrates enters cytoplasm and cleaves back to acetyl-coA and oxaloacetate Acetyl-CoA becomes malonyl-CoA through acetyl-CoA carboxylase
Malonyl-CoA forms fatty acids through fatty acid synthase complex

36
Q

What is the key regulatory enzyme in lipogenesis?

A

Acetyl-CoA carboxylase

37
Q

What are the 2 molecules that increase activity of acetyl-CoA carboxylase?

A

Insulin and citrate

38
Q

What are the 2 molecules that decrease activity of acetyl-CoA carboxylase?

A

Glucagon and AMP

39
Q

What enzyme is used for fat mobilization?

A

Hormone sensitive lipase

40
Q

What is the effect of glucagon and adrenaline on lipolysis?

A

Activates hormone sensitive lipase

41
Q

What is the effect of insulin on lipolysis?

A

Inhibits hormone sensitive lipase

42
Q

What are 3 key differences between fatty acid synthesis and fatty acid beta oxidation?

A

Fatty acid oxidation occurs in mitochondria, synthesis in cytoplasm
Fatty acid oxidation is oxidative, synthesis is reductive
Fatty acid oxidation inhibited by insulin, synthesis stimulated

43
Q

What are the 2 ways that lipids are transported in blood?

A

Bound to albumin

Carried as lipoprotein particles

44
Q

Where is cholesterol synthesised?

A

Liver

45
Q

How is cholesterol transported around body?

A

As cholesterol ester

46
Q

How does cholesterol form cholesterol ester?

A

Using LCAT or acyl-coenzyme A cholesterol acyltransferase

47
Q

What is the structure of lipoproteins?

A

Micelles

48
Q

What are the 4 components of the structure of lipoproteins?

A

Peripheral apolipoproteins
Integral apolipoproteins
Phospholipid mono layer with some cholesterol
Cargo

49
Q

What are the 5 distinct classes of lipoproteins?

A 
Chylomicrons 
VLDL 
IDL 
LDL 
HDL
50
Q

What are the 2 main carriers of fat?

A

Chylomicrons and VLDL

51
Q

What are the 3 main carriers of cholesterol esters?

A

IDL
LDL
HDL

52
Q

What is the relationship between particle diameter and density of lipoproteins?

A

Inverse

53
Q

What apolipoprotein is present in VLDL, IDL and LDL?

A

ApoB

54
Q

What apolipoprotein is present in HDL?

A

apoAI

55
Q

What are the three roles of apolipoproteins?

A

Packaging water insoluble lipid
Cofactor for enzymes
Ligands for cell surface receptors

56
Q

How do chylomicrons transport dietary fat?

A

Chylomicrons loaded in small intestine and apoB-48 added
Enters thoracic duct then left subclavian vein into blood, getting apoC and apoE
apoC binds lipoprotein lipase on adipocytes and muscle and chylomicrons release fats

57
Q

What happens after chylomicrons releases its fats?

A

ApoC dissociates and chylomicron becomes chylomicron remnant
Chylomicron remnants return to liver
LDL receptor on hepatocytes binds apoE
chylomicron remnant taken up by receptor mediated endocytosis

58
Q

What is the function of lipoprotein lipase?

A

Hydrolysis triacylglycerol in lipoproteins using ApoC-II

59
Q

Where can lipoprotein lipase be found?

A

On capillary walls of muscle and adipose

60
Q

What is the function of VLDL?

A

Transporting triacylglycerol to other tissues

61
Q

What are the 3 apolipoproteins are used by VLDL?

A

apoB109 added during formats, apoC and apoE added from HDL particles in blood

62
Q

How does VLDL transport TAG to other tissues?

A

VLDL binds to LPL on endothelial cells in muscle and adipose and releases triacylglycerol

63
Q

How are IDL particles led formed?

A

If VLDL a content depletes to 30% it becomes short lived IDL

64
Q

How does a LDL particle form?

A

IDL loses apoC and E when content depleted to 10% and becomes LDL

65
Q

What is the function of LDL?

A

Provide cholesterol from liver to peripheral tissues

66
Q

How do peripheral cells take up LDL?

A

They express LDL receptors and LDL has apoB-100 which is a ligand for the receptors and take up LDL via receptor mediated endocytosis, fuses with lysosomes for digestion to release cholesterol and fatty acids

67
Q

Why do LDL have longer half lives than VLDL or IDL?

A

They don’t have apoC and apoE so are not efficiently cleared by liver LDL receptor

68
Q

What is the effect of LDL having a longer half life than VLDL or IDL?

A

It’s more susceptible to oxidative damage and when oxidized, macrophages take them up and transform to foam cells which can form atherosclerotic plaques

69
Q

What are 3 ways to synthesize HDL?

A

In liver and intestine
Bud off from chylomicrons and VLDL as they are digested by LPL
Free apo-I acquire cholesterol and phospholipid from other lipoproteins and cell membranes to form HDL

70
Q

How do nascent HDL mature?

A

Accumulate phospholipids and cholesterol from cells lining blood vessels, filling hollow core and become more globular

71
Q

What does HDL do?

A

Remove cholesterol from cholesterol-laden cells and return to liver, facilitated by ABCA1 protein, converting cholesterol to cholesterol ester by LCAT hence reducing likelihood of foam cell and atherosclerotic plaque formation

72
Q

What are the 3 possible fates of mature HDL?

A

Taken up by liver via specific receptors

cells requiring additional cholesterol can use scavenger receptor to obtain cholesterol from HDL

HDL can also exchange cholesterol for TAG with VLDL via action of cholesterol exchange transfer protein

73
Q

What is the function of chylomicrons?

A

Transport dietary triacylglycerol from intestine to tissues

74
Q

What is the function of IDL?

A

Short lived precursor of LDL, transports cholesterol made in liver to tissues

75
Q

What is hyperlipoproteinaemia?

A

Raised level of one or more lipoprotein classes caused by over production or under removal

76
Q

What is type I hyperlipoproteinaemia?

A

Raised plasma level of chylomicrons, caused by defective lipoprotein lipase

77
Q

What is type IIa hyperlipoproteinaemia?

A

Defective LDL receptor - raised level of lipoproteins

78
Q

What is type III hyperlipoproteinaemia?

A

Defective apoproteinE leads to raised IDL and chylomicron remnants

79
Q

What is hypercholesterolaemia?

A

High levels of cholesterol in blood

80
Q

What are 3 symptoms of hypercholesterolaemia?

A

Xanthelasma - yellow patches on eyelids
Tendon Xanthoma - nodules on tendon
Corneal arcus - obvious white circle around eye

81
Q

How does raised serum LDL form plaques ?

A

Oxidized LDL, recognized and engulfed by macrophages, lipid laden macrophages become foam cells accumulate in intima of blood vessel walls to form a fatty streak, which evolve into atherosclerotic plaque, grows and blocks the lumen of the artery

82
Q

How does serum LDL increase the chance of stroke and myocardial infarction?

A

Formation of atherosclerotic plaque which grows and encroaches on artery lumen, increasing chance of rupture, triggering acute thrombosis by activating platelets and clotting cascade

83
Q

What are the 4 ways elements in the first approach of treatment of hyperlipoproteinaemia?

A

Reduce cholesterol and saturated lipids in diet
Increase fibre intake
Increase exercise
Stop smoking

84
Q

What are the 2 drugs to use if lifestyle changes are not effective at treating hyperlipoproteinaemia?

A

Statins and Bile salt sequestrants

85
Q

How do statins treat hyperlipoproteinaemia?

A

Reduce cholesterol synthesis by inhibiting HMG-CoA reductase

86
Q

How do bile salt sequestrants treat hyperlipoproteinaemia?

A

Bind bile salts in GI tract, forcing liver to produce more bile acids using more cholesterol

Metabolism, Endocrinology and Haematology (8 decks)

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