Lipids Flashcards

(107 cards)

1
Q

What is the general structure of fatty acids

A

Straight hydrocarbon chain (-CH2 units) terminating in methyl- (-CH3) and carboxyl group (–COOH)
Polar (hydrophilic, ‘water-loving’, -COOH) and non-polar (hydrophobic, ‘water-hating’, -CH3) ends
Chain length = 2 to 26 carbons
May contain up to 6 double bonds between carbons

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2
Q

What are the two types of conformation produced by double bonds in fatty acids

A

Cis and trans

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3
Q

Which conformation inserts a 30 degree angle and takes up more space/ is more fluid

A

Cis

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4
Q

Which two fatty acids are essential

A

Alpha linolenic acid and linoleic acid

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5
Q

How is the position of the double carbon bond indicated in fatty acids

A

The n- or ω- sign followed by the carbon atom from the methyl (CH3) end, stating that the FA belongs to either the n-3, n-6 or n-9 family of fatty acids (i.e. the first double bond starts on the third (n-3), sixth (n-6) or ninth (n-9) C atom from the methyl (CH3) end of the fatty acid
The D sign followed by the number of the carbon atom(s) at which the double bond(s) start from the -COOH end, e.g. D6,9,12,15

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6
Q

How many carbon atoms and double binds does this fatty acid have: 18:2 n-6

A

18 carbon atoms, 2 double bonds

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7
Q

What is the position of the 1st double bond from the methyl end in this fatty acid c18:2 n-6

A

6

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8
Q

What is the formula for alpha linolenic acid

A

C18:3 🔼9,12,15
n-3 or w-3

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9
Q

What is the formula for linoleic acid

A

C18:2 🔼9,12
n-6 or w-6

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10
Q

Describe short chain fatty acids

A

(C<6) occur free. Acetic, propionic, butyric most common

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11
Q

Describe long chain fatty acids

A

Long chain FA (C>12) either saturated (SFA), monounsaturated (MUFA) or polyunsaturated (PUFA)

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12
Q

What are fattty acids the building blocks for

A

A cylglycerols (MAG, DAG, TAG)

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13
Q

What is the normal end point for fatty acid synthesis in the cell cytoplasm

A

C16:0 SFA (palmitic) normal end point for FA synthesis in cell cytoplasm (malonyl pathway)

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14
Q

Where does chain lengthening and desaturation take place

A

Chain lengthening and desaturation take place in smooth endoplasmic reticulum

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15
Q

Describe chain lengthening

A

Elongase enzymes add 2C (from acetyl CoA) to the carboxyl end of the FA chain

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16
Q

Describe desaturation

A

Desaturase enzymes remove 2H in the presence of O2
Specific desaturases for inserting specific double bonds: D9, D6, D5 desaturases insert double bonds at C9, C6 and C5 respectively

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17
Q

Describe fatty acid synthesis in full

A

Formation of malonyl CoA: Carboxylation (add COO-) of acetyl CoA by acetyl CoA carboxylase (contains biotin to carry COO-). Requires ATP. Occurs in cell cytoplasm.
Sequential addition of a molecule of acetyl CoA to 7 molecules of malonyl CoA to yield palmitate (C16:0) by FA synthase. Requires NADPH (niacin)

Elongation via elongase enzyme – Addition of acetyl-CoA (donor of C2 units) to palmitate (and other LCFA after palmitate) to form FA-acyl-CoA, NADH and NADPH + 2H+ is the donor of 4H atom (i.e. 2 x CH2)

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18
Q

What are essential fatty acids

A

PUFAs which are essential for maintenance of health
Cannot be synthesised through normal synthetic pathways in animals further than 9 (lack Δ12, Δ15 desaturase enzymes)
Must be present in the diet so called Essential Fatty Acids (EFAs)
There are two EFAs - one in the n-6 family and one in the n-3 family

Linoleic acid 18:2 D9,12 (n-6)
a-linolenic acid 18:3 D9,12,15 (n-3)

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19
Q

What do cells that have requirements for FA with more than 18 carbon atoms and double bonds further from carboxyl group than C9 do

A

Synthesise them from the two Essential FA

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20
Q

Which fatty acids synthesised from EFA are most important

A

acid (the n-6 series) are g-linolenic acid (C18:3), dihomo-g-linolenic acid (C20:3) and arachidonic acid (C20:4)
The most important synthesised from a-linolenic acid (the n-3 series) are EPA (20:5) and DHA (22:6)

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21
Q

What are TAGs

A

Triacylglycerols (TAGs) are energy storage lipids in plants and animals
Esters of glycerol and FAs
Major dietary lipids

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22
Q

What are Phosphoacylglycerols (phospholipids) (PAG)

A

Major components of all biological membranes
Esters of glycerol with 2 FA and phosphoric acid
Additionally highly polar molecules bond to the phosphate group

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23
Q

Describe the role of PAG in the cell membrane

A

Amphipathic (Hydrophilic phosphate head
Hydrophobic FA hydrocarbon tail)
Fluidity of membrane determined by the component FAs – more PUFA more fluid. Important for cell

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24
Q

What are sterols

A

Amphipathic ring structures
Synthesised from Acetyl CoA

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25
What is the most important sterol in animals
Cholesterol
26
How are sterols stored
As cholestrol esters
27
What is the function of cholesterol
Cholesterol needed for bile acid production Steroid hormones derived from cholesterol Present in diet and synthesised in liver
28
What are the major lipids in the diet
Triacylglycerols (TAGs) – oils and fats Phosphoacylglycerols (phospholipids) Cholesterol, cholesteryl esters
29
Describe lipid digestion in the mouth
Digestion started by lingual lipase secreted from serous glands under the posterior tongue Lingual lipase present at birth, and stimulated by feeding pH optimum of ~4.5-5.4 so not active until reaches stomach
30
Describe lipid digestion in the stomach
Gastric lipase secreted by chief cells in stomach pH optimum ~4.0-5.0 Lingual and gastric lipases both active in stomach. In humans gastric lipase probably most important. Gastric and lingual lipases remove FA at the sn-3 position (or sn-1). Primarily get DAG formed (FA either at 1,2-DAG or 2,3-DAG positions) Do not need bile salts or colipase Primarily active against short and medium chain FA The DAG and FA formed together with PAG from the diet form an emulsion as a result of mechanical mixing in the stomach
31
Describe lipid digestion in the small intestine
More mechanical mixing and emulsification before further digestion Bile synthesised in liver and secreted into SI via bile duct in response to cholecystokinin (CCK) Bile salts are amphipathic so emulsify lipid (micelles) Lipolytic enzymes secreted by pancreas include: Pancreatic lipase (TAG), Phospholipase A1 and A2 (PAG), cholesterol esterase (CE) Pancreatic lipase attacks sn-1 and sn-3 position of TAG and DAG giving sn-2 MAG and FFA Needs colipase for full activity
32
Describe the role of cck in lipid digestion
Fat entering the duodenum stimulates CCK release by enteroendocrine cells CCK stimulates secretion of pancreatic enzymes and procolipase CCK also stimulates gall bladder contraction to expel bile into the duodenum
33
Describe how procolipase is activated to colipase
A 5 amino acid peptide fragment removed from N terminus of procolipase by trypsin to give active colipase
34
Describe the role of colipase in lipid digestion
Colipase (about 100 amino acids) thought to bind to pancreatic lipase causing a conformational change which makes it more active and/or act as anchor to keep lipase adjacent to micelles and/or possibly change surface of micelle to allow lipase access to TAG
35
What is the function of phospholipases
Phospholipases remove FA at sn-1 (A1) and sn-2 (A2) giving lysophopholipids (LPAGs)
36
Describe the role of cholesterol esterase
Cholesterol esterase hydrolyses cholesteryl esters to release free cholesterol
37
Describe the role of bile in lipid digestion
Derived from cholesterol in liver and are amphipathic so assist in formation of micelles (polar to surface, non-polar to centre) Reabsorbed in ileum and recirculated
38
Describe absorption of lipids into the enterocyte
Micelles containing lipid digestion products pass through unstirred water layer and can be adjacent to enterocytes Some passive absorption – able to pass through non-polar part of lipid membrane Some dependent on specific transport proteins e.g. FABP (fatty acid binding protein) and FAT (fatty acid transport protein)
39
Describe what happens after lipids are absorbed into the enterocyte
Within the enterocyte the FA re-incorporated into TAG Either esterify with glycerol or with MAG Incorporated into chylomicrons (or VLDL – very low density lipoproteins) (covered in lipids) Secreted across basolateral membrane and enter lymph
40
Describe microbial lipid digestion
Microbes digest nutrients to provide energy for their own growth Gut microbes are anaerobes or facultative anaerobes Generate energy through fermentation rather than oxidative phosphorylation (low ATP yield) Over 30% of dry weight of microbes is protein End products of fermentation (waste products for microbes) excreted to their surroundings Symbiotic relationship in gut: Host provides ‑ nutrients, warmth, region suitable for growth Microbes provide ‑ waste products which have nutrient value to the host produced from material which otherwise would have no nutrient value
41
How are lipids transported in the blood
Transported either bound to specific transport protein (retinol binding protein, vitamin D binding protein) or as lipoprotein complexes as cannot be transported freely in the blood
42
What determines the different classes/ functions of lipoproteins e.g. LDL, VLDL
Varying proportions of: triacylglycerols (TAG), phosphoacylglycerols (PAG, phospholipids), free cholesterol (FC), cholesteryl esters (CE) and apoproteins
43
What is the main function of apoproteins
Mediate lipoprotein remodelling/ type of lipoprotein
44
Which lipoproteins contain apoproteins Apo B-100
VLDL, IDL, LDL
45
What is the functions of Apo B-100 apoprotein
Ligand for LDL receptor (LDLR)
46
What type of lipoproteins contain Apo B-48
Chylomicrons, remnants of
47
What is the function of Apo B-48
Secretion of chylomicrons from intestines
48
What lipoproteins contain Apo E
Chylomicrons, VLDL, IDL, HDL
49
What is the function of Apo E
Ligand for binding of IDL and remnants to LDLR and LRP (for lipoprotein recognition)
50
What lipoproteins contain Apo C-II
Chylomicrons, VLDL, IDL, HDL
51
What is the function of Apo C-II
Activator of lipoprotein lipase (allows uptake of TAG from chylomicrons and LDL)
52
Where are Apoproteins found in lipoproteins
Withinin phospholipid monolayer
53
What does the density of the lipoprotein suggest
The lower the density the higher the ratio of lipid:protein
54
What are chylomicrons
Lipoprotein produced in enterocytes that transport of dietary TAG from small intestine to adipose tissue and heart and skeletal muscle
55
What are the main apoproteins in chylomicrons
ApoB-48 core structural protein ApoC-II allows recognition and binding to lipoprotein lipase (LPL) on capillary wall. Lipoprotein lipase is activated
56
How does chylomicron gain apoproteins
Peripheral apoproteins are gained from exchange of PAG with HDL
57
What is the function of lipoprotein lipase (LPL)
LPL hydrolyses TAGs in the chylomicron core to yields free fatty acids (FFA) which pass across capillary wall and into target cells
58
What happens to the during lipid exchange of the chylomicron with HDL
Surface PAG, free cholesterol, ApoC and ApoE picked up by HDL Chylomicron remnant, high in cholesterol esters, goes to liver
59
What are VLDL
Very low density lipoproteins produced in liver hepatocytes that are secreted via exocytosis into circulation and transport de novo TAG and free cholesterol from liver to adipose tissue, the heart and skeletal muscle
60
Describe the action of LPL on the VLDL
LPL hydrolyses TAGs in the VLDL core to yield FFA which pass across capillary wall and into target cells
61
What are the main apoproteins in VLDL
ApoB-100 core structural protein ApoC-II allows recognition and binding to lipoprotein lipase (LPL) on capillary wall
62
How does VLDL gain peripheral apoproteins
Peripheral proteins gained from exchange of PAG with HDL
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What happens during lipid exchange of VLDL
Surface FC, PAG picked up by HDL ApoC and ApoE transferred to HDL. The remaining lipoprotein, high in CE, now called VLDL remnant [or intermediate density lipoproteins (IDL)]. IDL retain ApoB-100 and ApoE.
64
What are chylomicron and VLDL remnants
Chylomicron and VLDL remnants [IDL] are particles which have lost TAG and some of their peripheral proteins but still have ApoE (via lipid exchange with HDL) ApoE allows recognition and uptake by liver High in CE, pro-atherogenic (higher risk of plaque)
65
What is LDL
Low density lipoprotein formed from VLDL and IDL that contains high levels of CE for transport to liver or peripheral tissues, and ApoB-100 (integral protein)
66
What allows LDL to bind to LDLR receptors
ApoB-100 allows recognition and binding to LDL receptors (LDLR)
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What happens when ApoB-100 in LDL binds to LDLR
Binding of ApoB-100 to LDLR initiates endocytosis giving vesicles with LDL inside pH drop releases LDLR which recycle to cell membrane Vesicles containing LDL fuse with lysosomes
68
What is LDLR
LDLR is glycoprotein present on surface of target cells
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Describe degradation of LDL
Degradation of lipids (remaining TAG, CE, PAG) and apoprotein from LDL occurs in lysosome Amino acids and free fatty acids released for cell metabolism Free cholesterol can enter cell FC pool (use for membranes or steroid synthesis) Free cholesterol may be converted to Cholesterol esters by enzyme ACAT (acyl CoA: cholesterol acyl transferase) for storage
70
What is HDL
High density lipoproteins produced in the liver that are involved in reverse cholesterol transport and contain integral structural proteins ApoA-I and ApoA-II
71
How do HDL receive PAG, ApoC and ApoE
Via lipid exchange with chylomicron and VLDL remants [IDL]
72
What is reverse cholesterol transport
Excess FC from cell membranes in peripheral tissue taken up by HDL FC is converted into CE via lecithin:cholesterol acyl transferase (LCAT) Some CE delivered directly to liver [anti-atherogenic] (reduces risk of plaque) ApoE recognised by liver facilitate uptake of HDL
73
What is the function of CETP
cholesteryl ester transfer protein (CETP) is secreted into plasma, mainly bound to HDL CETP enables the exchange of TAG and CE between lipoproteins CETP promotes the transfer of CE from HDL to VLDL, VLDL remnants [IDL] and LDL*, and enables HDL to take up TAG from VLDL and chylomicrons.
74
What enhances reverse cholesterol transport
Initial uptake of cholesterol by HDL enhances reverse cholesterol transport via indirect pathway whereby HDL and CE are delivered to liver via VLDL, IDL and LDL
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Where is CETP synthesised
Liver
76
What could be a potential therapy for atherosclerosis (plaques)
Inhibiting CETP
77
Why is HDL anti-atherogenic
Anti-atherogenic (enriched in cholesterol, PAG) Cholesterol transported from peripheral cells to liver for excretion in faeces via bile Also: anti-oxidant anti-inflammatory anti-thrombotic anti-apoptotic
78
What is the primary role of HDL in cholesterol transport
Transports excess cholesterol from cells to liver
79
What is the association between cholesterol and cardiovascular diseases
High plasma cholesterol is a risk factor for CVD. More particularly - combination of high LDL-cholesterol, low HDL-cholesterol and high TAG in plasma LDL-cholesterol associated with development of atherosclerosis: Linked to oxidation of LDL cholesterol by Reactive Oxygen Species (ROS)
80
How does oxidative stress in LDL lead to cardiovascular disease
Damaged LDLs by oxidative stress/ reactive oxidation species accumulate beneath ‘leaky’ endothelial monolayer of arterial walls Oxidised LDL removed by macrophages (WBC) Causes high concentration of cholesteryl esters in macrophages – lipid droplets. These are called foam cells and give rise to fatty streaks Cells in fatty streaks produce collagen as extra-cellular protein. Gives rise to fibrous plaque which narrows arterial lumen Reduced blood flow encourages blood to clot
81
How can we reduce the risk of atherosclerosis
by reducing total fat consumption and altering fatty acid composition e.g. more MUFA, n-6 PUFA, n-3 PUFA (high HDL cholesterol and low LDL cholesterol) and less trans FA (high LDL cholesterol and low HDL cholesterol)
82
What is the metabolic function of glycerol (from chylomicrons, VLDL)
Glycerol mainly metabolised in liver (kidney, muscle, brain), converted to glyceraldehyde 3-phosphate and can be used in glycolysis or gluconeogenesis depending on the energy state of individual Glycerol within cell cytosol are reincorporated into TAG and PAG PAG used membrane biosynthesis TAG energy store liver and adipose tissue
83
What is the metabolic function of free FA (from chylomicrons, VLDL)
FFA can undergo β-oxidation in mitochondria to yield acetyl-CoA which enters TCA (Krebs/citric acid) cycle (not erythrocytes, CNS) In the starved state (CHO and protein insufficiency) FFA can undergo ketogenesis in the liver to form ketone bodies as energy supply for the brain, heart and skeletal muscle following depletion of glycogen stores FFA within cell cytosol are reincorporated into TAG and PAG PAG used membrane biosynthesis TAG energy store liver and adipose tissue
84
What is the metabolic function of FFA from TAG
Long-chain FA (LCFA) derived from the essential fatty acids (EFA) linoleic acid (C18:2 n-6) and α-linolenic acid (C18:3 n-3) used in synthesis of: Eicosanoids (classic and non-classic) Endocannabinoids (affect mood, behaviour) Lipoxins and resolvins (inflammation) Formation of lipid rafts (cell signalling)
85
What are Eicosanoids
Large group of compounds derived from C20 PUFA
86
What are examples of eicosanoids
Arachidonic acid (AA, C20:4 n-6) Eicosapentanoic acid (EPA, C20:5 n-3) Docosahexanoic acid (DHA, C22:6 n-3) (Derived from essential FA)
87
How are eicosanoids synthesised
Synthesised by oxidation reaction catalysed by either cyclooxygenase (COX) or lipoxygenase.
88
What does cyclooxygenase form
Prostaglandins Prostacylins Thromboxanes (Types of eicosanoids)
89
What does lipoxygenase form
Leukotrienes (eicosanoids)
90
Which eicosanoids are derived from arachidonic acid via COX
2- series prostaglandins and 2-series thromboxanes
91
Which eicosanoids are derived from arachidonic acid via lipoxygenase
4 series leukotrienes
92
Which eicosanoids are derived from Eicosapentanoic acid via COX
3 series prostaglandins and 3-series thromboxanes
93
Which eicosanoids are derived from Eicosapentanoic acid via lipoxygenase
5 series leukotriene
94
What are the functions of thromboxanes
Thromboxanes (platelets) Act as vasoconstrictors Stimulate platelet aggregation Increase blood pressure
95
What are the functions of prostaglandin
Prostaglandins Affect smooth muscle contraction Act as vasodilators Reduce blood pressure Inhibit gastric secretion Are locally inflammatory
96
What is the function of prostocyclins
Prostacyclins (arterial wall) Act as vasodilators Inhibit platelet aggregation Reduce blood pressure
97
What is the function of leukotrienes
Leukotrienes Potent muscle contractants Are inflammatory Constrict airways in lungs
98
What is the difference between eicosanoids from the EPA (n-3) family to those from the arachodonic acid (n-6) family
Eicosanoids from the EPA (n-3) family are thought to be less potent/have opposite effects to those from the arachidonic acid (n-6) family. Effect varies with concentration.
99
What is conjugated linoleic acid (CLA)
Conjugated linoleic acid (CLA) is a group of polyunsaturated fatty acids—specifically, isomers of linoleic acid—distinguished by a unique conjugated double bond structure within the fatty acid chain (C18:2 FA where double bonds are conjugated i.e. with no –CH2- between) Often mix of cis- and trans- double bonds CLA is found in the meat and dairy products of ruminant animals such as cows and sheep, formed as intermediates during the biohydrogenation of dietary unsaturated FA (linoleic acid) by rumen bacteria Classified as functional food (‘beneficial effect beyond nutritive value’).
100
What are the claimed properties of CLA
Inhibit carcinogenesis Decrease body fat, increase protein deposition Modulate immune system Prevent atherosclerosis Reduce incidence of diabetes May function by conversion into C20 derivatives from which inhibitors of eicosanoid action may be produced
101
What are PPARS
PPARs (Peroxisome Proliferator Activated Receptors) are receptors which some PUFA can bind to They interact with specific sites on DNA and modify proteins produced
102
What is the influence of PPARs
Influence: synthesis of lipid and apoproteins in liver differentiation of adipocytes effect of insulin on adipose tissue metabolism
103
What is leptin
Hormone secreted by adipose tissue (Larger adipocytes produce more leptin)
104
What are the functions of leptin
An inhibitor of food intake A stimulator of energy expenditure A signal to the reproductive system Haematopoiesis Growth of new blood vessels
105
What are the UK DRVs for fats
Total fat intake (as TAG): 33% total energy intake (incl. alcohol) 35% of total food energy Total FA intake: 30% total energy intake (incl. alcohol) SFA ~10% total dietary energy cis-MUFA ~12% total dietary energy cis-PUFA ~6% total dietary energy trans-FA ~2% total dietary energy
106
What is the average cholesterol intake
100-400mg/day
107
Is cholestrol required in the diet
No dietary requirements as tissues can synthesise cholesterol - liver and intestinal epithelium particularly Dietary cholesterol has relatively little influence on plasma cholesterol