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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
What is the effect of glucagon on gluconeogenesis and how is it achieved?
Stimulates gluconeogenesis, increases amount of PEPCK and increases amount and activity of Fructose 1,6-bisphosphatase
26
What is the time course of glucose utilization from after feeding?
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
27
Where is dietary triacylglycerol metabolized before being used or stored?
``` Small intestine (TAG to fatty acid + glycerol) Intestinal epithelial cell - TAG to chylomicron ```
28
What is the effect of excess glycogen storage?
Tissue damage
29
What is the effect of diminished glycogen stores?
Hypoglycaemia and poor exercise tolerance
30
What is the function of glycogen in liver?
Buffer of blood glucose levels
31
What is the function of glycogen in muscle?
Enters glycolysis for energy production
32
Where is triacylglycerols stored?
Adipose tissue
33
Why is triacylglycerols an efficient energy store?
Energy content per gram is twice that of carbohydrates or proteins
34
What happens to triacylglycerols when they are metabolized before being stored or used?
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
35
What are the 5 steps in lipogenesis?
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
What is the key regulatory enzyme in lipogenesis?
Acetyl-CoA carboxylase
37
What are the 2 molecules that increase activity of acetyl-CoA carboxylase?
Insulin and citrate
38
What are the 2 molecules that decrease activity of acetyl-CoA carboxylase?
Glucagon and AMP
39
What enzyme is used for fat mobilization?
Hormone sensitive lipase
40
What is the effect of glucagon and adrenaline on lipolysis?
Activates hormone sensitive lipase
41
What is the effect of insulin on lipolysis?
Inhibits hormone sensitive lipase
42
What are 3 key differences between fatty acid synthesis and fatty acid beta oxidation?
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
What are the 2 ways that lipids are transported in blood?
Bound to albumin | Carried as lipoprotein particles
44
Where is cholesterol synthesised?
Liver
45
How is cholesterol transported around body?
As cholesterol ester
46
How does cholesterol form cholesterol ester?
Using LCAT or acyl-coenzyme A cholesterol acyltransferase
47
What is the structure of lipoproteins?
Micelles
48
What are the 4 components of the structure of lipoproteins?
Peripheral apolipoproteins Integral apolipoproteins Phospholipid mono layer with some cholesterol Cargo
49
What are the 5 distinct classes of lipoproteins?
``` Chylomicrons VLDL IDL LDL HDL ```
50
What are the 2 main carriers of fat?
Chylomicrons and VLDL
51
What are the 3 main carriers of cholesterol esters?
IDL LDL HDL
52
What is the relationship between particle diameter and density of lipoproteins?
Inverse
53
What apolipoprotein is present in VLDL, IDL and LDL?
ApoB
54
What apolipoprotein is present in HDL?
apoAI
55
What are the three roles of apolipoproteins?
Packaging water insoluble lipid Cofactor for enzymes Ligands for cell surface receptors
56
How do chylomicrons transport dietary fat?
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
What happens after chylomicrons releases its fats?
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
What is the function of lipoprotein lipase?
Hydrolysis triacylglycerol in lipoproteins using ApoC-II
59
Where can lipoprotein lipase be found?
On capillary walls of muscle and adipose
60
What is the function of VLDL?
Transporting triacylglycerol to other tissues
61
What are the 3 apolipoproteins are used by VLDL?
apoB109 added during formats, apoC and apoE added from HDL particles in blood
62
How does VLDL transport TAG to other tissues?
VLDL binds to LPL on endothelial cells in muscle and adipose and releases triacylglycerol
63
How are IDL particles led formed?
If VLDL a content depletes to 30% it becomes short lived IDL
64
How does a LDL particle form?
IDL loses apoC and E when content depleted to 10% and becomes LDL
65
What is the function of LDL?
Provide cholesterol from liver to peripheral tissues
66
How do peripheral cells take up LDL?
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
Why do LDL have longer half lives than VLDL or IDL?
They don’t have apoC and apoE so are not efficiently cleared by liver LDL receptor
68
What is the effect of LDL having a longer half life than VLDL or IDL?
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
What are 3 ways to synthesize HDL?
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
How do nascent HDL mature?
Accumulate phospholipids and cholesterol from cells lining blood vessels, filling hollow core and become more globular
71
What does HDL do?
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
What are the 3 possible fates of mature HDL?
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
What is the function of chylomicrons?
Transport dietary triacylglycerol from intestine to tissues
74
What is the function of IDL?
Short lived precursor of LDL, transports cholesterol made in liver to tissues
75
What is hyperlipoproteinaemia?
Raised level of one or more lipoprotein classes caused by over production or under removal
76
What is type I hyperlipoproteinaemia?
Raised plasma level of chylomicrons, caused by defective lipoprotein lipase
77
What is type IIa hyperlipoproteinaemia?
Defective LDL receptor - raised level of lipoproteins
78
What is type III hyperlipoproteinaemia?
Defective apoproteinE leads to raised IDL and chylomicron remnants
79
What is hypercholesterolaemia?
High levels of cholesterol in blood
80
What are 3 symptoms of hypercholesterolaemia?
Xanthelasma - yellow patches on eyelids Tendon Xanthoma - nodules on tendon Corneal arcus - obvious white circle around eye
81
How does raised serum LDL form plaques ?
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
How does serum LDL increase the chance of stroke and myocardial infarction?
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
What are the 4 ways elements in the first approach of treatment of hyperlipoproteinaemia?
Reduce cholesterol and saturated lipids in diet Increase fibre intake Increase exercise Stop smoking
84
What are the 2 drugs to use if lifestyle changes are not effective at treating hyperlipoproteinaemia?
Statins and Bile salt sequestrants
85
How do statins treat hyperlipoproteinaemia?
Reduce cholesterol synthesis by inhibiting HMG-CoA reductase
86
How do bile salt sequestrants treat hyperlipoproteinaemia?
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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