Lipids Flashcards
(104 cards)
1
Q
What are lipids
A
Heterogeneous organic molecules - hydrophobic (soluble in organic solvents)
2
Q
Where do lipids exist
A
- cell membranes
- as lipid droplets in adipocytes (adipose tissue)
- in blood lipoproteins
3
Q
What are the biological functions of lipids (6)
A
- Stored form of energy
- structural element of membranes
- enzyme cofactors
- steroid hormones
- vitamins A,D,E,K
- signalling molecules
4
Q
What can imbalances/deficiencies in lipid metabolism lead to
A
Major clinical problems e.g. obesity, metabolic diseases…
5
Q
Lipid classes (5)
A
- Fatty acids
- Triacylglycerol
- Phospholipid
- Glycolipid
- Steroids
6
Q
What can FA be classed as?
A
- Saturated - no C=C double bonds
- Unsaturated - one/more C=C double bonds that kink the hydrocarbon chain
7
Q
What “types” of FA are there
A
- Essential FA
- Good fats (cardiovascular)
- bad fats (cardiovascular)
- really bad fats
8
Q
Essential FA
A
Must get these from plants - linoleic and a-linolenic
9
Q
“goof fats” (cardiovascular)
A
high in polyunsaturated fatty acids (e.g. vegetable oils; sunflower/olive oil etc.)
10
Q
“bad fats” (cardiovascular)
A
high in saturated FA (e.g. stearic (beef))
Saturated fats play a role in myelination of nerve fibres and hormone production.
11
Q
“really bad fats”
A
trans FA, results from hydrogenation of vegetable oils (e.g. hard margarine (man-made))
12
Q
Why must we ingest essential FA
A
Humans cannot introduce double bonds beyond carbon 9
13
Q
Omega-3 FA (essential FA)
A
Derived from linolenic acid as essential FAs. Lowers plasma cholesterol, prevents atherosclerosis, lowers TAG, prevents obesity, reduces inflammation.
14
Q
Arachindonic acid (essential FA)
A
Precursor of eicosanoids that can be synthesized from linoleic acid
15
Q
Essential FA deficinecies
A
Rare, occuring mostly in infants caused by bad diet. Signs: scaly dermatitis, alopecia, thrombocytopenia, and intellectual disability.
can result in depresssion - deficincy of lipid signalling molecules
ADHD - lower levels of omega3 lead to behavioral problems.
16
Q
Triacylglycerols (TAG)
A
Esters of fatty acids and glycerol. Dietary fuel and insulation. Water soluble TAG coalesce into lipid droplets in adipose tissue (major component)
17
Q
Phospholipids
A
Amphiphatic - glycerol bound to two fatty acids and phosphate. Hydrophilic head and hydrophobic tail.
18
Q
What are phospholipids critical for
A
Aqueous/non-aqueous interfaces:
* Membranes
* Lipid droplets
* Local signalling molecules
19
Q
Steroids (inc 3 main classes)
A
Lipids with ring system, 3 main classes:
* Cholesterol - tarting material for synthesis of bile salts, steroid hormones and other components
* Steroid hormones - chemical messengers (sex hormones…)
* Bile salts - sodium salts of steroids used for emulsification
20
Q
Cholesterol
A
Component of cell membranes, precursor to sterol hormones, bile acids and vitamin D. Made in liver, found only in animal foods.
21
Q
What can cholesterol be made from
A
Acetyl CoA
22
Q
how is synthesis of cholesterol regulated?
A
Statins inhibit HMG-CoA reductase that is essential in cholesterol synthesis, lowers LDL levels, reduce risk of cardiovascular disease.
23
Q
LDL
A
Low Density Lipoprotein
24
Q
Eicosanoids
A
Class of lipids derived from 20 carbon unsaturated fatty acids and are synthesized throughout body. Signaling molecules derived from omega 3/6 FAs. Precursors to prostaglandins, thromboxanes, leukotrienes. Short half life (metabolised rapidly), produced and act locally
25
What do eicosanoids regulate
* Lipid infalmatory response
* Other... (see more questions on sub-types of eicosanoids)
26
What do prostaglandins regulate
Pain and fever, reproductive functions, mucus production in stomach.
27
What do prostacyclin regulate
Blood pressure
28
What do thromboxanes regulate
Blood clotting induction / platelet homeostatis
29
What do leukotrienes regulate
SMC constrictions and bronchioconstriction
30
What dose asprin do?
Inhibits COX enzymes and prostaglandin synthesis which reduces inflammation and fever. Also inhibits thromboxanes which cause clotting.
31
Zadirlukast
orally administered leukotriene receptor antagonist
32
Zileuton
orally active inhibitor of 5-lipoxygenase (inhibits leukotrines formation)
33
How does degree of unsaturation affect melting point of FA
More unsaturated = lower mp (less intermolecular forces)
34
Whats a glycolipid
lipids with a carbohydrate attached by a glycosidic (covalent) bond
35
What are steroids synthesised from
cholesterol
36
What are eicosanoids precursers of?
Prostaglandins, thromboxanes and leukotrienes
37
What are our diatery lipids
**TAG** (main one), phospholipids, cholesterol, cholesterol ester, free FA
38
What is the main site of **lipid digestion**
small intestine
39
Lipid digestion of pancreatic enzymes (lipases)
Promoted by emulsification (dispersion) by bile salts and peristalsis (mixing)
40
Bile salts
Derivative of cholesterol, act as biological detergents to form emulsions and micelles, saves lipids coalescing in aqueous environment
41
Digestion of TAG
Degraded in small intestine by pancreatic lipase to monoacylglycerol and two fatty acids
42
Digestion of cholesterol esters
Digested to cholesterol and free fatty acids.
43
Digestion of phospholipids
Hydrolysed to fatty acids and lysophospholipids.
44
Summarise the process of the digestion of lipids
Fat --*bile acids (duodenum)*--> emulsified fats --*lipases(small/large intestine)*--> FA and glycerol
45
Uptake of digested lipids
Products of lipid digestion form **mixed micelles with bile salts**. Mixed micelles approach brush border membranes of enterocytes and release lipid products which enter cells by diffusion. However, (short/med chain) fatty acids don't need micelles for absorption
46
Steatorrhea
Illness caused by lipid malabsorption due to defects in bile secretion, pancreatic function or intestinal cell uptake. **Excess fat in faeces** - float
47
Effect of removal of gall bladder
inhibits digestion/absorption of fats
48
What do intestinal cells do to TAG/PL/CE
resynthesise them for export
49
How are **insoluble** FA utilised/digested
Packaged with apoB-48 (solubilising protien) into **chylomicrons** for export
50
What happens with chylomicrons
Released by **exoxytosis** into lymph then blood
51
What happens when blood chylomicrons reach tissue?
TAG in chylomicrons is **hydrolysed to fatty acids and glycerol by lipoprotein lipase**. This enzyme is found mainly in capillaries of skeletal muscle and adipose tissue. Leftover FAs used for **energy or turned into TAG for storage**. Glycerol used in liver to make G3P (glycolysis and gluconeogenesis)
52
What are chylomicrons depleated of TAG called
Chylomicron remnants - go to liver
53
how are free FA transported in blood?
In complex with serum albumin (aka NEFA). This is the most abundant plasma protein with 2-7 binding sites for FA.
54
What are the majority of FA and how are they transported?
Esterified - lipoproteins
55
Why are lipoproteins necessary
TAG/cholesterol esters (CE) are insoluble in water - can't be transported in blood/lymph as free molecules
56
Structure of lipoproteins
Hydrophobic core (hold CE...) with a hydrophilic surface (unesterfied cholesterol, pholsholipids...)
57
How are lipoprotein classified and give the classes
By density (least to most):
* Chylomicrons
* VLDL
* LDL
* HDL
58
Chylomicrons
type of lipoprotien: TAG rich (take TAG from intestine to tissues)
59
VLDL
TAG rich. Transports TAG from liver to tissue
60
LDL
Cholesterol rich. Brings cholesterol to extrahepatic tissue - Bad cholesterol but dec with staffin drugs
61
HDL
Protein and cholesterol rich. Brings cholesterol from tissue to liver for elimination - Good cholesterol
62
What happens if you have too much LDL
Caused by obesity or genetic defect. Leads to **artherosclerosis** - lipid develops into **fatty straks and plaque in artery**
63
Summarise lipid digestion/absorption
Ingested lipids (e.g TAG) are cleaved by enzymes (e.g., pancreatic lipase), absorbed in the small intestine, and then transported in chylomicrons via the lymphatic system into the bloodstream, where they reach the liver (for lipoproteins), peripheral tissues (energy) and adipose tissue (storage)
64
How are lipids transported?
Circulating lipids are transported in lipoproteins (contain hydrophilic apolipoproteins) because the hydrophobic lipids are insoluble in plasma.
65
What else is broken down and released in lipolysis
breakdown and release of adipocyte triglyceride (TAG to free FA and glycerol)
66
Where does liver take up FA from
Plasma
67
2 major fates of FA taken up from plasma in the **liver**
1. Oxidation - energy source for liver and production of ketones - **burn**
2. TAG or lipid formation - local store for liver energy, distributed to other tissues like VLDL - **store**
68
What is reqired for long chain FA transport to michochondria
Carnitine shuttle
69
Lipid metabolism/oxidation summary
FA + CoA ---> Fatty acyl CoA ---- TAG (synthesis) **or** B-oxidation to CO2/ketone bodies
70
How are lipids metabolised in the **fed** state
Insulin elevated, stimulates ACC to convert acetyl CoA to malonyl CoA, which inhibits CPT-1 and means fatty acids accumulate and esterify to TAGs in cytosol.
71
how are lipids metabolised in the **fasted** state
Glucagon is elevated which stimulateds CPT-1 expression increasing fatty acid transport to mitochondria. FA oxidation is favoured.
72
Steps of Beta-oxidation
Dehydrogenation, hydration, dehydrogenation, thiolysis.
73
What happens each B-oxidation cycle
1 acetly CoA and a species **2 carbons shorter** than origional produced + 4 ATP
74
where does beta oxidation primarily occur
mitochondria
75
What is the purpose of B-oxidation
breakdown of FA for energy
76
Explain B-oxidation in the peroxisomes
Less ATP efficient, only happens to very long chain fatty acids, shortened fatty acids then move to mitochondria for further oxiidation
77
Can we use FA to make glucose?
No. Also can't convert acetyl CoA into glucose due to irreversible reaction pathway to make acetyl CoA
78
Ketone bodies
* Metabolites of fat
* energy source while fasting
* excess production if no insulin
* impaired use without insulin
* leads to diabetic ketaoacidosis
79
What happens when we have high levels of ketone bodies
Acidic - so make blood acidic (ketoacidosis)
80
What are ketone bodies
metabolites that replace glucose as the main fuel of the brain in situations of **glucose scarcity**, including prolonged fasting, extenuating exercise, or pathological conditions such as diabetes
81
When do we make ketone bodies
**fasting (used by tissues as energy source** - if not, then have sufficeint glucoes for glycolysis
82
Breakdown of ketone bodies for energy
Oxidised in mitochondria to give 2 GTP and 22 ATP. Transported from liver to other tissues (brain/skeletal muscle) and reconverted to acetyl CoA. Ketone bodies **can't be used by liver as fuel**, as liver lacks b-ketoacyl-CoA transferase (however, brain does have it)
83
What can happen when insulin is absent (diabetes)
Diabetic ketosis
84
How is fatty acid oxidation regulated
The rate-limiting step of fatty acid oxidation is the transport of fatty acyl-CoA to the mitochondria matrix through the carnitine system. - **entry into mitochondria and carnitine shuttle**
85
Where are ketone bodies made
liver
86
Where does FA synthesis occur
(tissues not cellular location)
* Liver
* Lactating mammary gland
* adipose tissue
87
De novo synthesis of fatty acids
* Occurs in cytosol, uses ADP and NADPH
* Acetyl CoA formed in mitochondria needs to be transferred to **cytosol**
* FA synthesised from acetyl CoA, derived from excess protein, fat and carbohydrate
88
What controls formation of malyonyl CoA?
Acetyl CoA Carboxylase (ACC)
89
Why is formation of Malonyl CoA important
It is a committed step in FA synthesis (stimulated by insulin) so no going back
90
Describe ACC
* Key regulatory enzyme
* Activated by citrate (signals enough glucose so make FA)
* deactivated by palmitoyl COA (enough FA made)
* insulin signalling activates (phosphorylation)
* glucagon, epinephrine deactivates (dephosphorylation) - inc levels of gucagon in fasting, want to break down FA, not synthesise them, hence deactivates
91
Is the synthesis pathway of FA different from the degredation?
Yes, uses different intermediates too - allows for better/easier control
92
Synthesis of fatty acids
* Every time 2 carbons are added in cycle
* carbons must come from malonyl CoA each time...
93
Elongation and desaturation
Further modification of palmitate or dietary FAs (e.g. ybsaturation/elongation/branching) occur in mitochondria and ER by diverse enzymes
94
What can't happen to essential FA?
| in terms of elongation and desaturation
Can't be **synthesised** but are required to make other lipids (eicosanoids)
95
Where are triglycerides generated
In the endoplasmic reticulum (ER) membrane
96
Compare FA synthesis and degredation
* **Synthesis** - cytosol, CoA, multiple enzymes used, Acetyl-CoA, NAD+/FAD
* **Degredation** - mitochondrial matrix, ACP, Enzyme complex, Malonyl-CoA, NADPH
97
Describe synthesis of free FA
fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes called fatty acid synthases. This process takes place in the cytoplasm of the cell.
98
essential fatty acid definition
polyunsaturated fatty acids (PUFA) that must be provided by foods because these cannot be synthesized in the body yet are necessary for health.
99
What kind of reaction is beta-oxidation
Catabolism
100
Structure of cholesterol
Cholesterol is a 27 carbon compound with a unique structure with a hydrocarbon tail, a central sterol nucleus made of four hydrocarbon rings, and a hydroxyl group
101
Function of cholesterol
helps your body make cell membranes, many hormones, and vitamin D. The cholesterol in your blood comes from two sources: the foods you eat and your liver. Your liver makes all the cholesterol your body needs.
102
How many carbons at a time are FA degraded and where?
2C at a time in the mitochondrial matrix
| (B-oxidation)
103
3 main steps of B-Oxidation
| Not dehydration... ect.
1. Fatty acid activation
2. transport into the mitochondrial matrix by the carnitine shuttle
3. degradation which has 4 main enzyme reactions.
104
What is cellular glycogen (in terms of movement)
Osmotically inactive - important benifit of storage
