Lipids Flashcards
1
Q
What are the 5 classes of lipids
A
- Fatty Acids
- Neutral Glycerides
- Phospholipids
- Sphingolipids
- Cholesterol Derivaties
2
Q
What is the general structure of fatty acids
A
R-COOH
R group is aliphatic
12-24 carbons long
3
Q
Are double bonds on fatty acids usually cis or trans
A
Naturally there are cis.
separated by one methylene group.
CH3-(CH2)n-COOH
4
Q
At higher temperatures are fatty acids solid like or fluid like?
Do double bonds increase or decrease the Tm?
A
Fluidlike. Unsaturated have lower melting points than satruated.
5
Q
What are neutral glycerides?
A
Neutral glcerides are glycerol molecules esterfied to fatty acids. ex: if attached to three fatty acids it is a triglyceride
6
Q
What are the three main components of a phosholipid structure
A
glycerol, 2 fatty acids, phosphate (phosphate can be attached to more things)
7
Q
What is a sphingosine? What happened when it is added to a fatty acid
A
It is a long chain amino alcohol. When added to a fatty acid it becomes ceramide
8
Q
What are two things that can be added to ceramide and create new types of sphingolipids?
A
If phosphatidylcholine is added it becomes a sphingomyelin
If a carbohydrate is added it becomes a glycospingolipid (ganglioside, globoside, cerebroside)
9
Q
What are 4 functions of cholesterol?
A
- Bile salt precursor
- vitamin d prescursor
- membrane component
- steroid hormones
10
Q
What component is used to make cholesterol
A
Acetyl Coa
11
Q
What is a lipoprotein? What is its function
A
Lipid Transport
All plasma lipoproteins are spherical particles consisting of a disorganized core of triglycerides and cholesterol esters surrounded by a thin lipid monolayer of cholesterol and phospholipid. Apolipoproteins are embedded in the surface lipid shell, with their hydrophobic domains oriented toward the core and their hydrophilic domains oriented outward.
12
Q
How are fatty acids transported
A
free fatty acids are NOT transported by lipoproteins but instead bind to albumin
13
Q
What is chylomicron
A
A lipoprotein. the lightest and largest of all of them. It is made in the intestine and transports dietary triglycerides to peripheral cells and liver
They are made mostly of triacylglycerols with very little cholesterol, protein or phopholipid
14
Q
What is the main apoprotein in chylomicron? What is th emechanism of lipid delivery?
A
B48, C E
Hydrolysis by lipoprotein lipase
15
Q
VLDL
A
80 nm diameter. go form liver to circulation bringing mostly endogenously made triglyceride to cells for storage or use
16
Q
What is the main protein of apoproteins? mechanism of lipid delivery
A
apoProtein: B100 C E
hydrolysis of lipoprotein lipase
17
Q
LDLs
A
from intravascular metabolism of VLDLs. Transport cholesterol to perihperal cells
18
Q
What is the apoprotein adn method of delivery for LDLs
A
B-100 and receptor mediated endoycytosis
19
Q
HDLs
what apoprotein
A
smallest, most dense. made and secreted by the liver and small intesting. they transfer cholesterol to IDL and LDL
apoprotein A
20
Q
What are the three kinds of gallstones
A
- CHolesterol dark greent o brown over 80% cholesterol
- Pigment stones: small and dark contain other parts of bile and less than 20% cholesterol
- Mized Stones: 20-80% cholesterol
21
Q
What are the three main enzymes lipases for lipid digestion?
A
- Gastric Lipase in stomach
- Bile Salts in SI– emusilfies triaglycerides to smaller particles, reused mostly
- PTL lipase from the pancreas breaks them down to a MAG and fatty acid. then bile salts further break down in micelles
22
Q
By what transport system to eneterocytes bring in lipids
A
enterocytes are inestinal mucoasa cells and they use the FATP4 transport system to bring in the fatty acids. within these cells they make chylomicrons
23
Q
What does lipoprotein lipase do
A
LPL
it hydrolyzes chlyomicrons and VLDL from the bloodstream. it creates chylomicron remnants
24
Q
what is steatorrhe
A
excess lipids in poop
25
Abetalipoproteinamia
apo- B-100 defect so that chylomicrons, vldl, ldl cannot be made. there is no long chain fatty acid absoprtion, gi symptoms, vitamin e cant be asorbed, cognitive problem
26
What are the disordders that could cause extreme chylomicron and triglyceride plasma levels
Apo 2-C definecy (protein on chylomicrons required for LPL), LPL defnicency, low LPL activity
27
What is the emchanism of "fake fats"
These potential drugs cannot be absorbed because they are not recognized by the highly specific lipases. ex: Olestra
28
Potential targets for anti-obesity drugs
1. fake fats
2 lipase inhibitors -orlistat
3. target fatp4
29
Where does B oxidation occur
inner mt matrix
30
how do fatty acids get into the mitochondria
carnitine shuttle
31
what are the enzymes used by carnitine shuttle
there is carnitine palmitoyl 1 (CPT 1) on the mt membrane and CPT 2 on inner mt membrane. between the fattty acyl coa is temporarily esterfied to carnitine.
32
what is made at the end of every b oxidation round
2 carbon shorter fatty acyl coA, acteyl CoA, nadh, fadh2
33
What happens with odd chain FA degradation
end up with one 3 carbon: propinoyl coa which during a further series of reactions requiring biotin and vitamin b12 as coenzymes you get succinyl Coa
34
How many ATP are made in the oxidation of a saturated fatty acid
Ex: 12:0
5 FADH2= 10 ATP
5 NADH= 15 ATP
6 Acetyl CoA= 72 ATP
-2 ATP for aceyl Coa synthesis
total 95 ATP
35
Which two diseases did we learn associated with fatty acid degradation
1. Zellweger
2. Refsum
36
Zellweger SYndrome
No functional peroxisomes to break down fatty acids of certain size. affects cns and elsewhere. patients font live over a year. Shows peroxisomes responsible for breakdown of long fatty acids
37
Refsum Syndrome
Cant degrade 3 methyl branched fatty acids called phytanic acid. get a build up. change diet to exclude fat containing products from ruminant animals, high fat fish
38
What organ are ketone bodies made in
mitochondria of Liver (for use in the brain)
39
what are the three kinds of ketone bodies
3 hydroxybutyrate
acetone
acetoacetate
40
which molecule do ketone bodies make that cna feed into a cycle
they all make acetoacetate which can be turned into 2 acetyl coas which go to the tca cycle
41
What is the main regulation of ketone body formation
release fo fatty acids from adipose tissue (probably hormonally controlled)
42
What is physiological ketosis
late pregnancy, the neonatal period, high fat (low- carbohydrate) diets, starvation and severe exercise. Total blood ketone body levels are mildly elevated but extra-hepatic usage matches hepatic output reasonably well.
43
what is pathological ketosis
there is no insluin so cells dont absorb glucose and no gluconeogenesis. leads to massive build up of ketone bodies
usually from insulin, sometimes alcohol
44
What is hypoketoic hypoglycemia? cause, symptoms, treatment
symptom of startvation because of insuffiecient utlization of fatty acids as primary energy source
symptoms: muscle weakness, sleepiness, mood changes
treat thtough diet to keep blood glucose levels constantly ok
45
What is the preferred energy source for the brain?
main fuel is glucose, can't do beta oxidation so under fasting it is ketone bodies
46
what is the preferred energy for muscle
glucose, ketone bodies and fatty acids. contains large glycogen stores. under resting conditions mostly beta oxidation, if glucose is used it is Cori Cycle
47
preferred energy source for adipose tissue
glucose and fatty acids. glucose needed to make glycerol to combine with fatty acids to make triglycerides for storage.
48
Kidney
GLucose, FAs, KBs
important site for gluconeogenesis
49
liver energy source
alpha keto acids from amino acid degradation under normal conditions. under starvation uses beta oxidation. liver makes ost ketone bodies but cannot use them because of CoA transferase not being expressed. Doesn't use glucose but makes it. when it does glycolysis it is just to make building blocks. Has glycogen storage.
50
Heart muscle energy source
does not store glycogen-very little glucose- mostly aerobic
-gets energy from ketone bodies and FAs
51
Where are fatty acids made
mostly in the liver but also adipose tissue
52
Where is fatty acid synthesis
Cytosol
53
How is acetyl coa brought to the cytosol for fatty acid synthesis
Regualted here at isocitrate dehdrogenase and citrate lyase
High levels of ATP stop isocitrate dehdro
High levels of ADP stop citrate lyase
54
Are fatty acids made during starvation?
No. Even though there is acetyl CoA and ATP there is no glucose intake so there are low levels of oxaloacetate in the liver so there can be no FA synthesis. Instead ketone bodies are made
55
What is the overall reaction to make Palmitate?
how many acetyl Coa, NADPH, H, ATP
requires 8 acetyl Coa (from amino acids, glucose); 14 NADPH, 14 H, 7 ATP
creates a 16:0 Fatty acid
56
What is the first and most important step of fatty acid synthesis in the cytosol? Does it require any cofactors
Acetyl CoA Carboxylase
forms Malonyl CoA
it is the rate limiting, committed step. Requires ATP, Biotin
inhibited by AMPK, increased by Citrate, decreased by palmitoyl CoA
57
Fatty Acid Synthase
What is its structure? How does it attach to intermediates?
It carries out the rest of fatty acid synthesis after acetyl coa carboxylase. It is adimer with two identical multifunctional polypeptides. Has a domain that is homologous to ACP
ACP is Acyl Carrier Protein in E. COli (has vitamin component) that attaches to the intermediates of fatty acid synthesis
58
How does alcohol affect the liver
It leads to an accumulation of NADH in the mitochondria which inhibits isocitrate dehydrogenase and leads to less glucose synthese
59
Where does chain elongation occur for fatty acid synthesis
At the SER Membrane. ELongation starts after 16B palmitate made.
60
DUring elongation how many carbons are added at a time? What is the donor and what is the acceptor
2 carbons. Acyl CoA is the donor and the acceptor is Malonyl CoA
uses multiple enzymes unlike first 16C
61
How are unsaturated fatty acids made and where
They are made on ER membrane by desaturases. It is direct oxidative desaturation
62
Where on the chain can humans add double bonds
omega 9, omega 6 omega 5. so we cannot saturate beyond carbon C
omega 6 and 3 are essential fatty acids.
63
Which enzyme inactivates carboxylase for FA synthesis
AMP activated protein kinase (AMPK)
It phophorylates carboxylase. AMPK is upregulated by AMP, down by ATP (allosterically)
64
Which enzymes activates carboxylase for FA synthesis? What regulates it?
Protein Phosphatase 2A (PP2A)
it removes the phophate group activating the enzyme. It is increased by insulin, decreased by glucagon/epi
65
What are all the way fatty acids syntheis is regulated
AMPK
PP2A
Citrate Lyase
Isocitrate Dehydrogenase
66
What happens to fatty acids during fasting, high fat diet, diabetes and high epi
Increased fatty acid oxidation and decreased fatty acid synthesis.
67
How are Lipogenic enzymes regulated
They all have similar promoter regions so expression is controlled easier
68
what are lipogenic enzymes
All the enzymes in FA synthesis.
acetyl coa carboxylase, FA synthase, citrate lyase, malic enzyme, DH of PPP (to make NADPH)
These are all increased in the long term by high CH diet, linsulin
decreased by: high fat/low CH diet, fasting
Short term are more affected allosteric or covalent modification
69
How do levels of Malonyl CoA effect CPT
inversely. when it is why there is less cpt so there is less beta oxiadtion
70
How do these things affect the levels of Acetyl CoA carboxylase?
1. AMPK
2. PP2A
3. Citrate
4. Palmitoyl CoA
1. inactivates it by phophorylation (increased by AMP, decreased by ATP)
2. activates it by dephophsylation (increased from insulin, decreased by glucagon/epi)
3. Increased by citrate
4. decreased by palmitoyl coA
71
How much does the number of adipose tissue change throughout a lifetime
generally set by teen years. unless extreme what changes it the cell volume
72
What happens in adipose tissue in a fed state (high insulin)
Glucose is converted into glycerol-P and acetylcoA which is made into fatty acids and combined to make triglycerides.
Chylomicrons and VLDL also feed into the fatty acids
73
What happens in a fasting state in adipose tissue
Triglycerides are converted to FA and glycerol by Hormone senstive lipase
-Lipolysis
74
How is hormone sensitive lipase controlled
when cAMP is made adenylate cyclase it binds to PKA activating it. When it is active it can ativate HSL by phosphoylation
75
How does insulin effect fatty acid release from adipose tissue
Insulin increaes PDE (phosphodiesterase) which facilitates the reaction turning cAMP into AMP so that HSL is never activated.
76
Leptin
Made by adipocytes so it is a adipokine. It decreaes hunger and increases caloric expenditure.
Long term effects
77
Ghrelin
made by the stomach it increases appetite
changes frequently (with every meal)
short and long term effects
78
Bile Salts
In mice increase brown adipose tissue activity, and prevents diet induced obesity and insulin depndent diabetes
they think in humans it incerases energy expenditure. maybe by creating heat
79
Phophoplipid degradation
Done by phopholipases. they are all specific to a different part of the phopholipid. Phopholipase C cleaves between glycreol and phophate
80
Where are sphingolipids degraded
in the lysosome
81
what causes tay-sachs disease
deficiency in enzyme to breakdown gangliosides ( a type of sphinoglipid with a carb attached to a ceramide).
leads to neurodegeneration, blindness, weakenss, seizures and red macula
82
What causes gangliosidosis
accumulation of gangiosides. neuro problems, red macula, big liver spleen, skeletal deformitites
83
What is Sandhoff disease
Accumulation of globosides
-similar to tay sachs but also visceral involvement
84
What is Fabry disease?
x linked globoside accumulation. rashes, kidney/heart failure, burning pain in extremeties
-enzyme replacement therapy available
85
What is Gaucher diseae
glucocerebroside accumulation
-most common lysosomal disease
big spleen liver, sometimes cns, osteoperosis
ERT avaialble
86
Niemann Pick (A +B)
accumulation of sphingomyelin
big liver spleen, neurodegenreative course, cherry red macula
87
Metachromatic Leukodystrophy
sulfatide accumulation
-cognitive problems, demylination, nerves stain
88
Krabbe Disease
Galactocerebroside accumulation. mental/motor deteriation. blindness/deafness, no myelin
89
What is Farber disease
ceramide accumulation
-joint dformity
90
What are all of the sphingolipidosis diseases
tay sachs
farber
gaucher
krabbe
fabry
niemann pick
gangliosidosis
sandhoff
metachromatic leukodystrophy
91
What things can go through the bilayer? partially? not at all?
ok: gases, small uncharged polar molecules
Patiral: water, urea
No: large uncharged polar ions, charged polar molecules, ions
92
What is the difference between and early and late endosome
Early is right after endocytosis and has the same pH as the blood. a late endosome has a pH drop because of proton pumps. It combines with primary lysosome to form secondary lysosome
93
What happens with the iron receptor
Transferring the receptor, is still on in the endosome but is released with the pH drop and the receptor is returned to the surface
94
what are the 4 functions of cholesterol
membrane component. precursor of bile salt, vitamin d and steroid hormones
- it can be made into a lot of different things
- enzyme definicies all lead to problems
95
is plasma cholesterol realted to death rate
yes
96
How much cholesterol is made per day in the body? what is it made from? how is it degraded
0.5 g/day in diet, .5 g/day from cytoplasmic synthesis
it is made form acetyl coA
no degradation pathway-they are excereted as bile salts
97
what is the most important enzyme in cholesterol synthesis. where is it
HMG-CoA Reducatase in the ER
-drugs target this enzyme
98
What is presented by cells that take up LDL
An LDL receptor. Do it by endocytosis. Receptor is recycled. Cholesterol is either stored or incorporated.
LDL receptor binds to Apo B
99
What is familial hypercholesterolemia
disorder ohigh-LDL cholesterol levels, mustation in receptor or apoB100. It is autosomal dominant
can be caused by:
no receptr
receptor not properly localized
low affinity for apo9 on reveptor (change in binding domain)
ldl recpeptor does not accumualte in coated pits (mutation in cytoplasmic domain)
100
What are cholesterol levels for heterozygous patients
happens to 1/500. blood cholesterol is over 300 mg/dl. The LDL levels are over 220 mg/dl
if untreated 85% have MIs before age of 60
give them statins
101
what happens with homozygrous FH patients
10^-6 frequency. blood cholesterol is 500-1200 mg/dl. MI before 30 if untreated. have to dialysis like treatment to remove LDL
-essential HMGcoA reductase is always 100% on.
102
What is SREBP
Sterol regulatory element binding protein
-a transcription factor for both LDL receptor and HMG coA reductase. It binds to to SRE on gene.
It is anchored to ER until is cleaved by protease and can go to nucleas. The protease is inhibited by cholesterol
103
What are target levels for
1. total cholesterol
2. LDL
3. HDL
4. Triglycerides
1. Under 200
2. Under 160
3. Greater than 45
4. Under 150
104
What happens to LDL if it has been in the bloodstream for a long time
They get oxidized. And get cleared out by macrophages. These accumualte in foam cells which can cause plaques
