Week 9 - Lipid Metabolism Flashcards
(106 cards)
1
Q
What are the ways in which lipids are categorised?
A
FA
Triacylglycerols
PL
Sterols
2
Q
Are lipids hydrophobic or hydrophilic?
A
Hydrophobic
But some are amphiphatic
3
Q
Describe carboxylic acids
A
Contain long alkyl chain w/ a carboxylic-acid group at 1 end.
4
Q
How many C atoms do the majority of fatty acids contain
A
16
5
Q
How many C atoms do short chain FA generally have
A
4-6 C
6
Q
How many C atoms do medium chain FA generally have
A
8-12 C
7
Q
How many C atoms do long chain FA generally have
A
14 or + C
8
Q
Double C bonds in sat + unsat FA
A
Sat = NO C=C bonds
Unsat = 1 or more C=C bonds
9
Q
What does the 1st no. of a FA represent?
i.e linoleum acid 18:2 (9,12)
A
No. of C atoms in FA
10
Q
What does the 2nd no. of a FA represent?
i.e linoleum acid 18:2 (9,12)
A
No. of double bonds
11
Q
What is the configuration of double bonds in naturally occurring FA?
A
Almost always cis
12
Q
How are unsat FA ID
A
By the position of the double bond closest to the methyl group
13
Q
How are trans double bonds introduced?
A
Manufacturing process
– Unsat FAs are hydrogenated to make them more solid.
14
Q
What are the 3 most common FAs
A
Palmitic acid
Oleic acid
Stearic acid
15
Q
What is palmitic acid called at a pH of 7
A
Palmitate
16
Q
What are the FAs that humans can’t make
A
Linoleic acid
𝛼-linolenic acid.
17
Q
Why are TAGs insoluble in H20
A
Due to large degree of hydrophobic hydrocarbon components.
18
Q
How many Kcal/g does fat provide
A
9Kcal/g
19
Q
How many kJ/g does fat provide
A
37kJ/g
20
Q
How many Kcal does 1kg of adipose tissue provide
A
7000Kcal
21
Q
Describe glycerol
A
3C mol
w/ 3 alcohol groups
22
Q
Define an ester
A
Comb. Of an acid + alcohol
23
Q
What does the physical state of a TAG depend on?
A
Length of C chain
No. of double bonds
24
Q
What does it mean in regards to melting points if the lengths of the FA chains re short + there’s more double C bonds
A
Lower melting points
25
Summarise TAG catabolism
TAG -- (HSL + H20) --> Diacylglycerol -- (HSL + H20) --> monoacylglycerol -- (H20 + monoglyceride lipase + HSL) --> Glycerol + 1 FA
26
Are PL diglycerides
YES
27
What is on the 3rd position of a PL
Phopshoric acid residue to which 1 of 4 different base groups attaches.
28
What are the 4 different base groups that can attach to the phosphoric acid on a PL
Choline
Inositol
Serine
Ethanolamine
29
What is the most abundant PL
Lecithin
30
Where are dietary fats mainly digested + by what?
Small intestine
By action of bile salts + pancreatic lipase
31
Briefly describe how the dietary fats are digested
Bile salts break large globules of fat --> smaller micelles (making them more accessible to lipase)
Pancreatic lipase converts TG--> monoglycerides, free FA + glycerol.
32
What is lipolysis
Hydrolysis of triacylgycerols (TAG) found in adipose tissue
33
When is lipolysis favoured?
In cond. of:
- ⬆️ energy need
- Low calorie dieting
- Fasting
- Cold body
34
What hormones enhance TG breakdown
Epinephrine
Norepinephrine
35
When are epinephrine + norepinephrine released
When sympathetic tone ⬆️
i.e during exercise
36
List other lipolytic hormones
Cortisol
Thyroid hormones
Insulin
37
What is the enzyme req for the hydrolysis of the 1st ester bond in TAG?
Adipose TG lipase
38
What is intramuscular TAG
TAG stored in skeletal muscle
39
What happens to intramuscular TAG when hydrolysed
FA generated are oxidised w/ in contracting fibre.
40
How is glycerol (from lipolysis) catabolised:?
Glycerol --> glyceraldehyde 3-phosphate
Then to glucose (if ATP supply in a cell is high = gluconeogenesis)
OR
Enters catabolic pathway to pyruvic acid (If ATP supply is low)
41
How are FA (from lipolysis) catabolised:?
In matrix of mit.
Enzymes remove 2C from long chains + attach it to CoA to form Acetyl-CoA which enters the TCA cycle.
Hepatocytes can take 2 Acetyl-CoA mol at a time + condense them to acetoacetic acid. The CoA is liberated but can't diffuse out of cells.
Some acetoacetic acid --> β-hydroxybutyric + acetone.
= The formation of these 3 ketone bodies is ketogenesis.
42
What % of energy from TAG comes from the FAs
95%
43
Are ketone bodies able to leave hepatocytes + enter blood stream?
Why?
Yes as they can freely diffuse through plasma membranes
44
What do other cells do after up taking acetoacetic acid
Attach its 4C (from acetoacetic acid) to 2 CoA mol to form...
2 Acetyl-CoA mol which can enter the TCA cycle for oxidation.
45
Can hepatocytes use the acetoacetic acid they make for ATP production?
Why?
No
As they lack the enzyme that transfers acetoacetic acid back to CoA.
46
Where does lipolysis take place
Locations other than in fat cells:
i.e, hydrolysis of dietary TAG in small intestine, by pancreatic lipase.
Hydrolysis of TAG in blood lipoproteins by lipoprotein lipase.
Intramuscular TAG is hydrolysed by a muscle-specific HSL, which generates FAs that are immediately available as a fuel for that fibre.
47
How many Kcal of H20 soluble fuel does the brain req per day?
500Kcal
48
Can FA be converted into glucose for the brain(i.e) to use?
no
49
Can CHO be converted into FA?
yes
50
Can aa be converted into FA?
YES
51
Can FA be converted into aa?
NO
52
What are the effects of insulin in the blood on muscle?
Inhibits muscle lipoprotein lipase = no fat breakdown
53
What are the effects of insulin in the blood on adipose tissue?
Stimulates lipoprotein lipase
Inhibits hormone sensitive enzyme lipase to prevent fat from being released into bloodstream.
⬆️ in chylomicrons = ⬆️ TAG, glycerol + FAs go into adipose tissue to be stored.
54
What are the effects of insulin in the blood on the liver?
Synthesis of new FAs, TAG + cholesterol
55
What is the feeding state?
Storing fat - feeding state
Just eaten.
Incr. blood glucose levels, incr. in lipids.
Stimulation of insulin = incr. insulin in blood which has an effect on 3 diff. organs:
Muscle, adipose tissue + liver
56
What is the fasting state?
Using Fat for Energy — Fasting State
Blood glucose levels start to drop, as been time since eating.
= Inhibits secretion of insulin = decr. Insulin in blood.
Glucagon release is stimulated.
57
What are the effects of glucagon in the blood on adipose tissue?
inhibits lipoprotein lipase to prevent breakdown of chylomicrons.
But stimulates thehormone sensitive enzyme lipase which breaks down fat —> bloodstream.
58
What are the effects of glucagon in the blood on muscle?
Stimulates the muscle lipoprotein lipase
59
What are the 2 pathways
Exogenous
Endogenous
60
Exogenous pathway
Cholesterol from dietary + biliary sources is absorbed in the intestine + enter circulation as a component of chylomicrons.
61
Endogenous pathway
Cholesterol is synth. by the liver + extra hepatic tissues + enters circulation as a component of lipoproteins or is secreted into bile.
62
What are the main lipid transport molecules
Chylomicrons
Lipoproteins
Albumin
63
Describe chylomicrons
Large lipoprotein particles containing TG packaged w/ cholesterol.
64
Where are chylomicrons synthesised
Small intestine
65
What happens once the chylomicrons have left the enterocytes?
Enter the lymphatic capillaries
Pass into blood stream
Deliver fats to tissues
66
Examples of lipoproteins
HDL
LDL
VLDL
67
What do lipoproteins allow the transport of
H20-insoluble fats w/in aqueous env.
68
Where can lipoprotein lipase be found
Capillary walls
69
What does lipoprotein lipase do
Hydrolyses TG --> FA + glycerol
70
What happens once lipoprotein lipase has hydrolysed TG?
FA + glycerol pass through capillary wall to tissues where they're oxidised for energy or re-esterised for storage.
71
What happens to fats that are synthesised endogenously in the liver?
Packaged into another type of lipoprotein = VLDL
To be transported to tissues where TG are extracted in the same way.
72
What happens when FA undergo β-oxidation?
Generates Acetyl-CoA.
Each round removes 2C from FA chain.
73
What does albumin transport
Un-esterified FA
74
What are the 3 main steps req. for the mobilisation of stored fat + oxidation of FFAA
Release of FFAA from TAG
β-oxidation of FFAA —> TCA cycle —> ATP
𝜶- oxidation of FFAA —> TCA cycle
75
Explain the release of FFAA from TAG
In order for lipolysis to occur, HSL needs to be activated by epinephrine or glucagon. -- Triggering a reaction that req. ATP.
Also activated protein kinase which also req ATP.
TAG breakdown by triglyceride lipase.
76
Fate of glycerol after the release of FFAA from TAG
β-oxidation can't occur in the adipose tissue
Glycerol can't be phosphorylated due to lacking glycerol kinase.
So, glycerol is transported in blood to liver.
77
Fate of glycerol after the release of FFAA from TAG
What happens once glycerol has been transported to the liver
Phosphorylated + converted to GLYCEROL PHOSPHATE then to DIHYDROXYACETONE-PHOSPHATE / DHAP which eventually becomes PYRUVATE.
-- All reversible
78
What happens once pyruvate becomes acetyl Co-A
Enters β-oxidation + not reversible
79
Fate of FFAA after the release of FFAA from TAG
Unesterified FA move through cell membrane of adipocyte.
Bind to albumin in plasma where they're transported to tissues where FA enter cells, get activated to CoA derivatives + oxidised for energy.
80
Why is it important that 2C fragments are removed from a FA at a time?
Allows 1 to calculate how much ATP is yielded from each of the FAs
81
Carnitine Shuttle
Allows Acetyl-CoA (hydrophobic) to cross inner mit. membrane from cytosol --> matrix where TCA cycle + β-oxidation occurs
82
What enzyme converts long chain FA to Acetyl CoA
CoA synthase / thiokinase
83
Carnitine
Mol. key to transporting acyl CoA into mit.
84
How is carnitine from mit. transported to cytosol?
By carrier protein translocase
85
What does CAT-1 / carnitine palmitoyltransferase I do in the cytosol
Facilitates the addition of an Acyl mol to carnitine + the regeneration of CoA.
Acyl carnitine can be transported into mit again by action of same carrier protein = translocase.
86
What does CAT-2 / carnitine palmytoyltransferase 2 do in the mitochondria
Catalyses the reaction of Acyl + CoA --> Acyl CoA + liberates carnitine
87
What size FA can cross the inner mit w/out CARNITINE
FA w/ less than 12C
88
When can FA enter the TCA cycle
Only if enough oxaloacetate has been generated from pyruvate.
89
Give a summary of the energy yielded from a 16C FA
16C broken down in 2s to become 14C, 12C...
FADH2 provides 2 ATP when oxidised w/ the ETC
NADH provides 3.
From a 16C FA = 14ATP from FADH2, 21 ATP from NADH + from the TCA cycle 96 in total == 131 ATP.
90
𝜶- oxidation
When there’s branched chain FA as they’re not substrates for Acetyl CoA dehydrogenase due to the methyl group present.
= Instead, branched chain FA are hydroxylated at the 𝜶-carbon by FA 𝜶-hydroxylase. — Product is decarboxylated + then activated to it CoA - a substrate for enzymes of β-oxidation.
91
Ketone bodies
H20 soluble, energy-rich compounds that are easily transported across cell membranes.
92
Give examples of ketone bodies
acetoacetate
β-Hyroxybutyrate
acetone
93
What are the special circumstances under which ketone bodies are only formed under?
Glucose deficiency i.e due to fasting or diabetes mellitus.
In this case, to supply extrahepatic tissues that can’t breakdown FA, the liver switches to gluconeogenesis + the breakdown of FA. — For this breakdown, β-oxidation splits FA in liver into acetyl CoA. Usually, the Acetyl CoA is further metabolised in the TCA cycle. But conversion of Acetyl CoA —> ketone bodies in ketogenesis ONLY starts when there’s a deficiency of oxaloacetate as well as low glucose.
94
What happens in diabetes mellitus
Cellular glucose uptake is inhibited, causing intracellular glucose deficiency
95
Liver doesn't use ketone bodies for its own energy supply, so what does it do with them?
Releases them into the blood for cells of the brain, skeletal + cardiac muscle cells.
96
What happens after ketone bodies have been released into the blood
They reach the extra hepatic tissues which absorb + convert them back into 2 mol of Acetyl CoA in ketogenolysis.
97
What happens with the 2 mol of Acetyl CoA after ketogenolysis in the extra hepatic tissues?
Enter TCA cycle as there's no oxaloacetate deficiency in the extra hepatic tissues so Acetyl CoA can contribute to the generation of ATP in the cells.
98
Why might there be a deficiency of oxaloacetate
Low glucose levels inhibit glycolysis so almost no pyruvate available to form oxaloacetate
FA degradation = accumulation of Acetyl CoA meaning amount of acetyl CoA is far more than the amount of oxaloacetate available to TCA cycle.
99
Describe the ketogenic diet
Very low CHO
High fat
Triggers the metabolic fasting state of the body
100
What happens in the ketogenesis process
Ketone bodies are formed from Acetyl CoA (arising mainly from breakdown of FA) in mit of hepatocytes.
101
Steps of the ketogenesis process
2 mol of Acetyl CoA -- (thiolase) --> Acetoacetyl-CoA
3rd mol of Acetyl CoA is used to convert Acetoacetyl-CoA --(HMG-CoA synthase)--> HMG-CoA
HMG-CoA -- (HMG-CoA lyase) --> Acetoacetate (ketone body). -- Acetyl CoA is cleaved from mol.
== To yield 1 mol of acetoacetate, 2 mol. of Acetyl CoA are needed.
Acetoacetate -- (β-Hyroxybutyrate dehydrogenase)—> β-Hyroxybutyrate (by being reduced).
102
What os the ketogenolysis process
Ketone bodies are converted back into acetyl-CoA which is fed into TCA cycle + used for ATP synth.
103
Steps in the ketogenolysis process
Acetoacetate -- (thiophorase)--> Acetoacetyl-CoA
Thiolase catalyses formation of AcetylCoA
104
Is acetone metabolised?
no
105
What happens instead with acetone as it isn't metabolised
Excreted as a metabolic end product in exhaled air.
106
Ketoacidosis
In type 1 diabetes mellitus
Serum pH below 7.3 — Drop is caused by acetoacetate + β-Hyroxybutyrate as they both have an acid group that cleaves its proton under physiological cond.
High levels of ketone bodies in blood + urine.
