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103 Cards in this Set

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  • Back
What do lipids do for us?
1) membrane structure
2) fuel
3) fuel storage
4) lipoprotein structure
5) signalling molecules
6) vitamins
How are lipids classified?
1) simple
2) complex
What are the three complex lipids and their primary function?
1)phospholipids and they are involved in structure of cell membranes, amphipathic molecules
2) triglycerides and they are a source of energy for the cell when there is oxidation of their fatty acids
3) sphingolipids and they dont exist in large amounts but are important signalling molecules for cell/cell interations and you find them in the membranes of cells
What are the fatty acids that are found in complex lipids characterized by?
1) number of carbons in the chain
2) number of double bonds
3) position of double bonds
What are simple lipids?
Based upon the structure of the CHO molecule, a ring structure that does not have a fatty acid attached to it, found in cell membranes to stabilize them and make them more rigid and hormones, vitamins and components of the electron transport chain all involved with simple lipids
Where does the chylomicron come from and what is it mainly composed of?
The gut and it is mainly triglyceride
What allows for the effective reaction between lipoprotein lipase and chylomicron?
apoprotein C
What allows the secretion of the chylomicron?
apoprotein B
What is the first thing that happens in lipid digestion?
a gastric lipase begins to breakdown the triglyceride into monoglycerides and free fatty acids and this is called an emulsion
What is the second thing that happens in lipid digestion?
pancreatic lipase is then secreted to get everything broken down to free fatty acid and monoglycerides and it enters through a mycell
What acts of lipids with pancreatic lipase?
Bile salts that get reabsopred in the distal ilium and also give pancreatic lipase more access to the di and triglycerides that have not yet been digested
What cells can't break down chylomicrons?
CNS
What tethers and grabs the lipoprotein lipase dimer on the endothelium?
A heparan and proteoglycan thing
What activity does the lipoprotein lipase have?
serine ester so it breaks ester bonds
What two fates does the fatty acid have once it is taken up by the cell?
1) Stay and be used in the formation of phospholipids or more triglycerides or cholesterol esters so basically biosynthesis or
2) it can enter the mitochondria and be oxidized all the way down to CO2 and water with the intended production of ATP
What happens to the glycerol molecule backbone?
It can be taken up by the cell and used as an intermediate in glycolysis or gluconeogenesis
What happens when lipoprotein lipase is not working right?
plasma triglycerides go way up and can cause pancreatitis
How do we get energy out of a fatty acid?
1) activation to fatty acid coA
2) transport into the mitochondria by the carnitine shuttle
3) beta oxidation and the production of acetyl coA and some ATP
4) ATP production from acetyl coA into the TCA cycle
Where is a fatty acid biosynthetic and where is it bioenergetic?
1) in the cytosol
2) in the mitochondria
Where are the enzymes for beta oxidation and the tca cycle?
in the mitochondria
How is fatty acid coA made?
It is made by acyl-coA synthetase which adds coA on the carboxy terminus making a thioester bond and atp is required
What are the characteristics of the acyl coA synthase enzyme?
1) catalyzes thioester bond formation
2) uses 2 high energy P bonds
3) specific for fatty acid chain length
What enzyme binds the fatty acid coA to carnitine?
Carnitine transferase
If we have a 16 carbon fatty acid how many acetyl coAs are we going to make?
8
What is and what is not inhibited by high concentrations of fatty acid?
Beta oxidation is not but TCA cycle is
What else can we do with acetyl coA instead of fed it into the TCA cycle?
make ketone bodies
Where are ketone bodies produced and where are they used as a fuel?
Produced in the liver and used by the tissues
What can be made by ketone bodies that can be found on the breath of diabetes patients?
acentone
Acetoacetate is being reduced to what by what enzyme to make the second ketone body that is secreted?
1) beta hydroxybutyrate
2) beta hydroxybutyrate dehydrogenase
What is the key enzyme in the liver for ketone body synthesis?
HMG coA synthase
What is the principal ketone body and what is the ratio of the two ketone bodies released into the bloodstream?
beta hydroxybutyrate and the ratio is 3:1 beta hydroxybutyrate: acetoacetate
What turns acetoacetate back into acetoacetyl-coA in the tissues?
succinyl coA transferase
What enzyme binds the fatty acid coA to carnitine?
Carnitine transferase
If we have a 16 carbon fatty acid how many acetyl coAs are we going to make?
8
What is and what is not inhibited by high concentrations of fatty acid?
Beta oxidation is not but TCA cycle is
What else can we do with acetyl coA instead of fed it into the TCA cycle?
make ketone bodies
Where are ketone bodies produced and where are they used as a fuel?
Produced in the liver and used by the tissues
What can be made by ketone bodies and on the breath of diabetics?
acetone
What is acetoacetate reduced to and by what enzyme?
1) beta hydroxybuturate
2) beta hydroxybuturate dehydrogenase
What is the enzyme that makes acetoacetate from acetyl-coA?
HMG coA synthase and it is a key enzyme in the liver
What is the principal ketone body and what is the ratio that the two ketone bodies are released into the blood stream?
1) beta hydroxybutyrate
2) 3:1 beta hydroxybutyrate:acetoacetate
What is the key enzyme in the ketone body metabolism?
Succinyl coA transferase
What does succinyl coA transferase use as a source of coenzyme A for making acetoacetyl coA from acetoacetate to activate ketone bodies?
succinyl coA
What is characteristic of SCOT, succinyl coA transferase defiency?
high ketone bodies especially in a starvation state
You get NADPH from which two places?
1) pentose phosphate shunt
2) malic enzymes
What do you need for de novo lipid biosynthesis?
1) 1 acetyl coA
2) 7 malonyl coA
3) ATP
4) NADPH
What enzyme clips the 6 carbon citrate into a 4 carbon and 2 carbon molecule?
ATP citrate lyase
What is the rate limiting enzyme in fatty acid biosynthesis and what form is it maximally active in?
Acetyl coA carboxylase and maximal in the filamentous form
What carrier protein does acetyl coA carboxylase use?
biotin
What reduces the double bonds in the fatty acid synthesis?
NADPH
What puts double bonds in our fatty acid?
Fatty acid coA desaturase
What is the precursor for eiconsanoids?
arachidonic acid with 20 carbons and 4 double bonds
How do we regulate fatty acid metabolism?
By the malonyl coA level so
1) by the activity of acetyl coA carboxylase
2) by the activity of carntine shuttle
What inhibits the enzyme acetyl coA carboxylase?
amp, glucagon, palmitoyl coa
What activates acetyl coA carboxylase?
insulin, citrate
What does malonyl coA bind to to block fatty acid access into the mitochondria?
carbonyl aceyl transferase 1
What is the ultimate carbon source for CHO and fatty acids?
acetyl coA
Which enzyme esterifies the fatty acids to the glycerol backbone to give you phophatidic acid?
aceyl transferase
What is key in the mobility of a membrane?
The ratio of saturated to unsaturated fatty acids
What do you need to make a phospholipid?
1) a backbone
2) fatty acids
3) polar head group
What is the main phospholipid in the membrane?
phosphatidylcholine
What does insulin do to the adipocyte in the well fed state?
1) increases lipoprotein lipase
2) increases glut 4 transporters
What activates hormone sensitive lipase?
PKA from CAMP from Glucagon
What is the main enzyme in liplysis?
hormone sensitive lipase
What are the major glycosalated forms of lipids?
Sphingolipids
What is every disease associated with sphingolipids due to?
an enzyme defect in the degradative pathway
What accumulates in Tay Sachs disease?
GM2 gangliosides
What are two characteristics of eiconsanoids?
1) they are made on demand
2) they operate locally
What kind of signalling do the eiconsanoids do?
autocrine
What are the major glycosalated forms of lipids?
Sphingolipids
What is every disease associated with sphingolipids due to?
an enzyme defect in the degradative pathway
What accumulates in Tay Sachs disease?
GM2 gangliosides
What are two characteristics of eiconsanoids?
1) they are made on demand
2) they operate locally
What kind of signalling do the eiconsanoids do?
autocrine
What do you have to have to make aracadonate?
1) essential fatty acids
2) elongation and desaturation reactions
What enzyme breaks ester bonds between fatty acid and position 2 of backbone to clip off aracadonate?
phospholipase A2
What does the cyclooxygenase pathway give you?
prostaglandins and thromboxans
What does the lipooxygenase pathway give you?
leukotrienes
What are the two pathways that come from aracadonate?
Lipooxyngenase and Cyclooxygenase
What dont the leukotriens have that the prostaglandins and thrombaxanes do?
a ring structure
What evokes prolonged smooth muscle contraction and mucosal edema in asthma?
Leukotrienes
Which COX is inducible?
COX 2
What are the two pathways to platelet activation? and what do both pathways facilitate?
1) phosphoinositide cycle
2) thromboxane synthesis
and both pathways facilitate
1) cytoskeleton rearrangement
2) fibrinogen receptor exposure
3) granule secretion
What does apoprotein b do?
for the release of chylomicrons and VLDL
What does apoprotein C do?
for the activation of lipoprotein lipase
What are the four functions of cholesterol?
1) membrane lipid
2) steriod hormones
3) vitamin D
4) bile acids
How do you make a cholesterol ester?
Esterify the OH on position three with a fatty acid
What are all the things acetyl coA does?
1) a source of energy for feeding the TCA cycle
2) a source of carbon for that energy
3) a precursor for the ketone bodies
4) used in synthesis of CHO
5) used in synthesis of fatty acids
What is the rate limiting enzyme in CHO synthesis, what does it make, and how is it regulated?
1) HMG coA reductase
2) mevalanoic acid
3) regulated transcriptionally
What are the four stages in cholesterol synthesis?
1) begin with acetate in the form of acetyl coA
2) make mevalonic acid with HMG coA reductase which is rate limiting
3)isoprene assembly and squalene formation
4) cyclization and cholesterol formation
What are the four levels of cholesterol regulation?
1) LDL concentration
2) number of LDL receptors
3) HMG CoA reductase
4) cholesterol ester synthesis
What does VLDL have on it that is specific to the liver?
B100
What does chylomicrons have on it that is specific to the gut?
B48
What is apoprotein b for?
release and endocytosis of remnants
What is apoprotein a for?
It is on lecithin for cholesterol acyl transferase (LCAT) activation
What is apoprotein e for?
It is for receptor mediated endocytosis of remnants
What is apoprotein d for?
It is for cholesterol ester exchange protein, CETP of HDL
What does the LDL receptor bind to in the membrane as it clusters?
Clathrin in the clathrin coated pits
What actually binds the cholesterol and stops scap from making the transcription factor?
sterol sensing domain
What enters the nucleus and acts as a transcription factor for several genes involved in lipid metabolism?
the n terminal domain of SREBP
What are the 5 classes of mutations of the LDL receptor?
1) Synthesis
2) Transport--> most common
3) LDL Binding
4) Clustering
5) Recycling
What is HDL mainly associated with?
apoprotein A and LCAT
What does HDL also serve as?
an apoprotein exchange