Lipid Metabolism Flashcards
1
Q
lipids (3)
A
- small, water insoluble containing fatty acyl groups, isoprenoid/sterol groups
- usually soluble in organic solvents
- amphipathic: often predominantly hydrophobic, but have polar hydrophilic regions
2
Q
functions of lipids (4)
A
- energy storage
- cell membrane
- signalling molecules
- insulation
3
Q
fatty acids (3)
A
- carboxylic acids containing long hydrocarbon chain
- can be saturated or unsaturated
- vary in # of carbons, # of double bonds, configuration of double bonds (cis/trans) an position of double bon
4
Q
saturated FA
A
- FA with no double bonds
5
Q
unsaturated FA
A
- FA contains double bonds
6
Q
nomenclature of FAs (4)
A
- total # of carbons
- total # of double bonds
- cis or trans double bonds
- position of double bonds in numerical order
7
Q
what ending is used for protonated acids (not ionized)
A
- “-ic acid”
- oleic acid
8
Q
what ending is use for de-protonated (ionized) acids?
A
- “-oate”
- oleate
9
Q
what factors affect FA melting point? (3)
A
- chain length
- # of double bonds
- trans fat or cis fat
10
Q
how does chain length affect FA MP?
A
- longer chain -> higher MP
11
Q
how does the # of double bonds in FA affect MP? (2)
A
- more double bonds -> lower MP
- double bonds introduce kinks in hydrophobic tails so the tails cannot pack as tightly
12
Q
MP in trans FA vs cis FA
A
- having cis double bonds -> lower melting temperature
13
Q
what configuration are most double bonds in nature?
A
- cis, trans that are products of incomplete hydrogenation cause cancer and heart disease
14
Q
triacylglycerols (TAG or triglycerides) (2)
A
- glycerol with all 3 -OH esterified with different or identical FAs
- neutral fats
15
Q
function of triacylglycerol (3)
A
- main storage form of FA in animals:
- FA are almost completely reduced (less oxygen) allowing harvest of more energy per gram than for carbohydrates
- TAG is hydrophobic: can store more TAG in a given volume compare to glycogen
16
Q
glycerophospholipids
A
- composed of glycerol backbone linked to 2 FAs (C-1 and C-2) and a phosphoester linkage to phosphate and a polar alcohol group (C-3)
17
Q
glycerophospholipid function
A
- membrane lipid
18
Q
sphingolipids
A
- sphingosine as a base with head group attached by -OH and FA chain
19
Q
sphingolipid function
A
- membrane lipid
20
Q
steroids (4)
A
- molecule containing core of 4 fuses of rings (A-D)
- A - C: 6 carbons
- D: 5 carbons
- planar geometry, rigid, and amphipathic
21
Q
sterol
A
- a steroid with a OH group on the C-3
22
Q
waxes (2)
A
- chemical esters of FA linked to long-chain alcohol
- highly hydrophobic
23
Q
eicosanoids (2)
A
- derived from arachidonic acid
- signalling molecule involved in inflammation
24
Q
membranes
A
lipid bilayers
25
3 major types of lipids in membranes (3) and common characteristic
- glycerophophoslipids
- sphingolipids
- sterols
- all are amphipathic
26
permeability of membranes (2)
- impermeable to big molecules and small, but polar molecules
- permeable to gases and small hydrophobic molecules
27
fluid-mosaic model of membrane (3)
- membrane is fluid lipid bilayer with proteins floating in it
- proteins and lipids can diffuse freely, but rarely flip-flop from layer to layer
- membrane has proper fluidity that needs to be maintained to ensure proper function
28
Tm
temperature at which phase transition occurs
29
T << Tm (2)
- liquid ordered state (crystalline)
| - membrane is too rigid
30
T >> Tm (2)
- liquid disordered state (liquid solid)
| - membrane is too fluid
31
how do organisms adjust membrane fluidity (2)
- bacteria can change FA composition of membrane lipids
| - eukaryotes have sterols in membrane (cholesterol in animals)
32
cholesterol when T < Tm
- cholesterol prevents tight packing of FA tails and prevents transition to semi-solid state
33
cholesterol when T > Tm
- cholesterol prevents free rotation of FA tails (enhances tighter packing), preventing transition to fluid-like state
34
when does FA synthesis occur (2)
- when there are excessive nutrients (carbs, lipids, proteins)
- convert excessive nutrients to FA and store as TAG in adipose tissue
35
generally, how does FA synthesis occur
- carbs and amino acids can be oxidized and degraded to acetyl-CoA, which is directly use to build FAs
36
where does FA synthesis occur (2)
- main sites: liver, adipose tissue and mammary glands during breast feeing
- located in cytosol (don't need organelles)
37
What is the general mechanism for FA synthesis (2)
- FAs synthesize by adding 2 carbons at a time in each cycle
| - only use acetyl-CoA for first 2 carbons, remaining use "activated form": malonyl-CoA
38
what are the 4 main steps in each cycle of FA synthesis (4)
1. condensation
2. reduction
3. dehydration
4. reduction
39
preparatory step of FA synthesis (3)
- conversion of acetyl-CoA to malonyl-CoA using CO2 and ATP
- enzyme: acetyl-CoA carboxylase (ACC)
- irreversible second reaction step
40
acetyl-CoA carboxylase (ACC)
- initiates FA synthesis by converting acetyl-CoA to malonyl-CoA
41
fatty acid synthase (FAS) in bacteria
- each step is catalyzed by single enzyme
42
fatty acid synthase (FAS) in vertebrates
- consist of one polypeptide chain with 7 functional domains with different activities
43
What are the 2 important reaction thiol groups of FAS
- acyl carrier protein (ACP): long, flexible phosphopantetheine group (derived B5 vitamin) that contains reactive thiol group
- cys residue side chain in beta-ketoacyl-ACP synthase (KS) domain that can bind acyl-groups
44
what end does chain growth occur in FA synthesis?
- carbonyl end; original acetyl group is at the end of the tail
45
how many cycles of FA synthesis do mammals go through?
- 7 cycles
46
what happens after the 7 cycles of FA synthesis?
- thioesterase (TE) hydrolyzes C16 (palmitate) from ACP
47
how do you make an other even-chain FA after FA synthesis cycles?
- it is done by a separate enzyme (sometimes called elongases) that extend a chain via the same mechanism
48
how do you make a odd-chain FA after FA synthesis cycles?
- synthesized by alpha-oxidation: removal of CO2 or by using propionic acid instead of acetate as a primer in FA synthesis
49
in humans, where do most odd-chain fatty acids come from?
- from dairy products that are produced by bacteria
50
how do you make a branched chain FA after FA synthesis cycles?
- mostly in bacteria, made by special branching enzymes
51
how do you make unsaturated FAs after FA synthesis cycles? (2)
- special enzymes called denaturases introduce double bonds
| - humans lack enzymes to introduce double bonds beyond C-9
52
which FAs are essential and why? (2)
- linoleic and linolenic acids are essential
| - they have double beyonds C-9, which is unable to be synthesized in humans
53
what is the first step of lipid catabolism?
- TAG in adipose tissue is broken down to glycerol and free fatty acids during starvation
54
what is the second step of lipid catabolism? (2)
- free FA are transported via bloodstream complexed with albumin
- tissues pick up FA from bloodstream
55
what is the third step of lipid catabolism? (2)
- FA oxidation: FAs are broken down into acetyl-CoA
- electrons from FA oxidation or from acetyl-CoA catabolism in Krebs cycle are "captured" in NADH/FADH2 form that go to ETC to produce ATP (oxidative phosphorylation)
56
where does FA oxidation take place?
- occurs in mitochondria of most tissues (except brain and RBCs)
57
acetyl-CoA carboxylase (ACC) (2)
- catalyzes committed step of FA synthesis
| - regulated allosterically and hormonally
58
how is ACC regulated allosterically? (2)
- citrate activates ACC (more citrate = more acetyl-CoA for FA synthesis)
- palmitoyl-CoA inhibits CoA (more palmitoyl-CoA = enough FA inside cell already, so less FA synthesis)
59
how is ACC regulated hormonally?
- hormones activate signalling cascades that lead to changes in phosphorylation status of ACC
- regulated by glucagon, insulin, and ATP:AMP levels
60
what is the activation of phosphorylated ACC?
- inactive
61
what is the activation of dephosphorylated ACC?
- active
62
when is glucagon released and how does it affect ACC regulation? (3)
- glucagon is released when blood glucose is low (not enough energy)
- glucagon binds receptor and activates signalling cascade that leads to activation of protein kinase A (PKA)
- PKA phosphorylates ACC (inhibits)
63
when is insulin released and how does it affect ACC regulation? (3)
- released when blood glucose is high (lots of energy)
- insulin binds to receptor and activates signalling cascade that leads to activation of phosphatase
- phosphatase dephosphorylates ACC (activates it)
64
how does ATP:AMP levels regulate ACC? (2)
- low ATP: high AMP (low energy state) activates special enzyme, AMPK
- AMPK phosphorylates ACC (inhibits FA synthesis)
65
how is carnitine-acyl-transferase (CAT I) regulated?
- malonyl-CoA allosterically inhibits CAT I, preventing beta-oxidation during FA synthesis
66
how is beta-hydroxyacyl-CoA dehydrogenase regulated?
- allosterically inhibited by NADH (product inhibition)
67
how is thiolase regulated?
- allosterically inhibited by acetyl-CoA (product inhibition)
68
cholesterol
- 27C molecule derive from acetyl-CoA
69
functions of cholesterol (3)
- maintaining proper membrane fluidity
- precursor for steroid hormones
- precursor for bile acids and salts
70
what are cholesterol sources? (2)
- exogenous: mainly animal, derived products
| - endogenous: we can synthesize it de novo (from scratch)
71
how do mammals break down cholesterol and consequences? (2)
- mammals cannot break cholesterol all the way to acetyl-CoA (although some bacteria can use cholesterol catabolism for energy)
- excessive amounts of cholesterol can be deposited on blood vessel walls and lead to atherosclerosis
72
where does de novo synthesis of cholesterol occur? (2)
- mainly in the liver
| - some happens in the intestines
73
HMG-CoA reductase? (2)
- major point of regulation is HMG-CoA reductase
| - regulated both locally and hormonally
74
what are the 3 ways that HMG-CoA is regulated locally? (3)
- transcription
- translation
- degradation
75
sterol regulatory element (SRE) and SRE binding protein (SREBP) (3)
- sequence of DNA before HMG-CoA reductase gene
- binding of SREBP to SRE initiates transcription of HMG-CoA reductase
- more SREBP enzyme = more cholesterol
77
how is HMG-CoA regulated through transcription? (3)
- SREBP is anchored in the membrane
- when cholesterol levels are high, SREBP will stay anchored in membrane = no activation of transcription
- when cholesterol levels drop, SREBP is released from the membrane and diffuses to membrane to start HMG-CoA transcription
78
how is SREBP released from the membrane? (3)
- ER membrane translocates to golgi
- golgi action of two proteases release SREBP from membrane
- free SREBP diffuses to nucleus
79
how is HMG-CoA regulated through translation?
- translation of HMG-CoA is inhibited by derivatives of mevalonate
80
how is HMG-CoA regulated through degradation?
- degradation of HMG-CoA reductase is stimulated by lanosterol (and 25-hydroxy-cholesterol)
81
how is HMG-CoA regulated hormonally? (3)
- HMG-reductase is activated by insulin induced dephosphorylation
- HMG-redustase is inactivated by glucagon induced phosphorylation
82
what are the cholesterol derivatives? (3)
- cholesterol esters
- bile salts and acids
- steroid hormones
83
cholesterol ethers: how is it related to cholesterol and function (2)
- FAs can form esters with -OH of cholesterol making it more hydrophobic
- allows storage and transports of cholesterol due to tighter packing
84
how and where is cholesterol ester synthesized? (2)
- synthesized in liver: by ACAT using FA-CoA
| - in HDL particles: by LCAT using phosphatidyl choline
85
bile salts and acids: (2)
- definiton
- purpose
- polar derivatives of cholesterol
- synthesized in the liver to help emulsify lipids in intestines and a way to excrete excessive cholesterol (not efficient and accumulation occurs)
86
steroid hormones (3)
- common precursor and # of classes
- what it is
- purpose
- 5 major classes with common precursor: pregnenolone
- more oxidized and compact than cholesterol
- helps cholesterol to cross cell membranes and bind DNA or intracellular receptors
87
characteristics of ACC
- ACC has biotin (vitamin B7) as a prosthetic group that is attached to Lys residue in active site of ACC
88
What are the sources of NADPH for FA synthesis? (2)
- conversion of malate to pyruvate
| - pentose phosphate pathway
89
What are the sources of acetyl-CoA for FA synthesis?
- carbohydrate and amino acid catabolism in the mitochondrial matrix
90
how are unsaturated FA oxidized? (3)
- enzyme: delta^2,delta^3-enoyl-CoA-isomerase
- monounsaturated FA require isomerase to reposition the double bond to allow hydration
- FADH2 is NOT produced, so there will be 1.5 less ATP produced
91
how are odd-chain FA oxidized? (3)
- broken down by same mechanism until 5C-acyl-CoA
- 5C-acyl-CoA is broken down to acetyl-CoA and propionyl-CoA
- propionyl-CoA is converted to succinyl-CoA (Kreb cycle intermediate) or used in gluconeogenesis
92
how are long-chain FA oxidized?
- oxidized in peroxisome until they are short enough to be transferred into mitochondria via carnitine shuttle
