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BMS 528- CH. 16: Lipid metabolism
Terms in this set (25)
Fat (triacylglycerol*) as the major energy reserve in most organisms
Fat is highly _____ (high energy yield) and _____ (no bound water)
- Fats yield high amounts of energy, they are in reduced form (CH2 or ___ groups). Can be ____ and give off the energy.
- Fats can also be stored in a space efficient way. They are ______, completely ______ (free of water). 100% mass stored is ______ energy.
- Glycogen on the other hand is ______ (absorbs large amounts of ____). Every gram of glycogen absorbs ____ grams of water. Stored glycogen only has _____ by mass of usable energy
primary sources of TAGS
- ____ ___ biosynthesis in the liver
- Storage depots in ______
- Because of their _____, fats are usually emulsified with bile salts or complexed with ______ as lipoproteins
Fats/ TAG are ___ ___ so absorption and transportation in blood stream (aqueous media) requires specialized _____.
- ____ ____emulsify TAG in the intestine
- ______ carry TAG and other lipids in blood stream
bile salts (TAG) are from __ and transported by __
TAG are from __ and transported by __
Bile salts emulsify TAGs in the intestine
TAGs are complexed with ____ __ in the intestine, then digested by pancreatic lipase into _____ and free ___ ___.
Free fatty acids are transported into the _____ system, resynthesized into TAG, then complexed with protein to form _____, the least dense of the ______.
Bile salts emulsify TAGs in the intestine
Bile salt molecule is made up of _____ cholic acid (cholesterol derivative) salt.
Bile salts are ____; Polar OH and COO- groups and nonpolar _____ rings.
Bile salts form ____ with TAG inside.
The bile salts form aggregates with Enzyme (___ ____) and Colipase. The Enzyme is ______ dependent, and ______ the Ester bonds in TAG. Reaction takes place at water/oil interface.
Products of Hydrolysis:
- ___ ___ ___
3 fatty acids
Generalized plasma lipoprotein structure
TAG are transported in the blood by ______.
Lipoproteins are soluble aggregates. Contains:
- Proteins (___)
- TAG (_____)
- Cholesterol Ester (inside)
- _____ (surface)
- Phospholipid monolayer (_____)
- Hydrophobic: ____ molecules, ___ ___ amino acid residues, cholesterol esters
- Hydrophilic: Hydrophilic amino acid residues from proteins, Hydrophilic head of _____. OH of cholesterols
_______ keep lipids emulsified after meal. (~500 mg/mL of blood after meal) 120 mg TAG, 220 mg Cholesterol, 160 mg Phospholipids
triacylglycerol is carried in body by micelle
formed with multiple molecules of bile salts and lipase to breakdown TAG into glycerol and 3 fatty acids
classification of lipoproteins
Each lipoprotein has a defined complement of associated ____, called ______
ex) A-I, A-II, A-IV, B-48, B-100, C-I, C-II, C-II, D, and E
- Density of Lipoprotein is related to ____ & ____ content of Lipoprotein.
- TAG density is ____, while protein density is ____.
- The higher the TAG content the ____ the density of the _____.
Density/proteins increase toward right
fat increases toward left:
Chylomicrons: Lipoproteins that carry dietary fat from ____ to ___ ___ (heart, ____, and adipose tissue)
VLDL: similar role but for newly synthesized _____ from the ____.
Both Chylomicrons and VLDL have their TAG hydrolyzed to ____ and ___ ___ by extracellular enzyme, ____ ___.
- C-II apolipoprotein activates _____ and hydrolyzes
- Released ___ ____ are absorbed by nearby tissue
Binding of a chylomicron to lipoprotein lipase on the inner capillary surface
Breakdown of chylomicrons (and VLDL) at capillaries for hydrolysis of TAG to glycerol and free fatty acids for uptake into cells
Lipoprotein lipase, like other lipases, is a member of the serine esterase family (like trypsin) with active site Ser, His, and Asp
Apo CII activates lipase
and is apo of to chylomicron
Liver orchestrates lipoprotein transport pathways to redistribute fat and cholesterol
Upon TAG hydrolysis both Chylomicrons of VLDL are converted to ___ and _____ rich remnants.
Chylomicrons -> ______ remnants
VLDL is recycled and converted to ____ during transit in _____. LDL is the principal form in which _____ is transported to ____.
HDL returns excess ____ from tissues to the ____
Synthesis of Lipoproteins are of crucial importance for liver health. Chronic Liver Cirrhosis (___ ___ degeneration) occurs if lipoproteins can not be ____ in liver. Damage to the Liver causes ___ to accumulate there because it can't be ____ to peripheral tissues.
Liver becomes ____ with fat.
dietary fat pathway:
fat->bile salt->micelle->chylmoicrons(CII)->CII lipases and there is remnant chylomicrons
VLDL->IDL(VDL rementants)->LDL->peripheral tissues->HDL then back to liver
LDL main role is to deliver cholesterol to peripheral tissues, HDL is left over LDL that once reaches maximum capacity of tissue is sent out and back to liver
Cholesterol transport and utilization in animals
Prolonged hypercholesterolemia hastens the formation of atherosclerotic plaque; total plasma cholesterol (cholesterol plus cholesterol esters) above 200 mg/100 mL is a major risk factor for __ ___ disease
Cholesterol in plasma lipoproteins exists as free ____ and _____ esters
Cholesterol and cholesterol esters are _____.
LCAT is ____: cholesterol acyl-transferase
Cholesterols have number of essential roles:
- Maintain ____ of membrane
- ___ to bile acids and ____
High levels can lead to ___ ___
the LDL receptor and cholesterol homeostasis
Brown and Goldstein studies on familial hypercholesterolemia (FH)
mg/mL of blood
Normal serum cholesterol <______
____ FH>>> 650-1000, death of heart disease by age 20
_______ FH>>> 350-500, death often in 30s or 40s or later
Brown and Goldstein used cultured fibroblasts to demonstrate cholesterol is taken up by the ____ ___
FH patients are deficient in ___ ___
These experiments identified a new process by which cells interact with their environment - receptor ___ ____
Cholesterol regulates its own level inside cells by controlling its de novo ____, storage, and ____ _____ density
LDL Homeostasis is important. Excess ___ in ___ form fatty streak. _____ become engorged with fatty deposits that harden into atherosclerotic plaques, leading to ____ ___
Overview of LDL receptors in cholesterol uptake and metabolism
Region that contains LDL receptor is called a "___ ___". The coated pit is lined with protein called ____ (can form cage like structures).
The LDL binds to its receptor and the complex is engulfed and taken into the cell (_____). Recognition occurs by _ -____, primary apolipoprotein on LDL (step 4,5)
Several Endocytotic Vesicles fuse together to form an _____ (step 6-7)
Endosome fuses with _____ containing hydrolytic enzymes. (step 8)
Breakdown releases __ __and ____ (step 10)
The receptor is recycled and moves back to ___ ___to pick up more ___. (step 9)
Cholesterol moves to ____, used for membrane ___--
overview of LDL receptors in cholesterol uptake and metabolism
Release of cholesterol results in 3 regulatory effects (step 1)
1. Reduces Cholesterol Synthesis by inhibiting __ ___reductase. _____ transcription of gene for this enzyme and _____ degradation of the enzyme.
2. Activates ___ __: cholesterol acyltransferase (ACAT). ACAT is an ____ enzyme that synthesizes ___ ___. Promotes ____ of cholesterol esters in droplets.
3. ___ transcription of the gene for ____ ____. Reduced synthesis of LDL ensures that cells do not take up more ____ than what is needed. If dietary levels of cholesterol are higher than what the cell consumes , LDL levels in blood ____, leads to ____ complications.
HMG - CoA reductase
decreases LDL receptor
regulatory effects TQ:
what happens upon a cell taking up cholesterol in form of LDL?
a. increased synthesis of cholesterol
b. decreased synthesis of LDL receptors
c. inhibition ( decrease) activity of HMG-Coa reductase
d. activation of ACAT
all above true
5 Mutations affect LDL receptor
1. Mutations that lead to insufficient __ ___in the endoplasmic reticulum (affects step ____ )
2. Receptor is synthesized but fails to migrate from the ____ to ___ ___ for transport to cell membrane (step ___). This is most _____ type of mutation.
3. Receptor is synthesized and processed normally but fails to bind to ____ (step ___ )
4. Receptor binds to LDL but fails to pinch off cell membrane in "___ ___". (step __ )
5. Receptor binds and internalizes LDL in coated pits but fail to release ____ in the endosome and do not ____ receptor to cell surface.
Cholesterol, LDL and atherosclerosis
- LDL subject to ____ - oxidized LDL can be taken up by __ ___ on white blood cells
- This process yields almost ____ uptake of _____ into a white cell and produces a cholesterol-gorged foam cell, which is a _____ to atherosclerotic plaque
There are no _____ pathways for cholesterol within the cell
____ can return excess cholesterol to the liver for passage through the __ ____ to the intestine, leading to excretion
LDL "__ cholesterol"; HDL "___ cholesterol"
Linolenic acid is an ____ fatty acids for humans. We ___ enzyme to synthesize it.
**LDL= L for LOSER!
***HDL= H for HAPPY :)
MOBILIZATION OF STORED FAT
Synthesis of TAG and its deposition in adipose cells is _____ (evident in prevalence of obesity in humans).
_____ Enzymes are involved. All are ____ esterases, catalyzing hydrolysis by acyl-enzyme intermediate.
- ____ triglyceride lipase (ATGL) catalyzes step __ TAG-> DAG
- ____ sensitive lipase (HSL) catalyzes step DAG->MAG
- _____ lipase (MGL) catalyzes step __ MAG-> glycerol
Fatty acids exit the adipocytes by ___ __. Carried in blood by ____, released to tissue.
happens during fasting-> glucagon
hormonal regulation of fat
Hormonal regulation of HSL and ATGL is controlled by hormonal binding to __ ___ receptors, leading to activation of Adenylate Cyclase to synthesize ____.
This leads to ___ ___ dependent signal transduction phosphorylation cascade.
Depending on the state of cell the hormone can be:
____ (during fasting), ______ (stress, fight or flight), Parathyroid hormone, ____, Adrenocorticotropin
All of these stimulate ____.
Fatty acids exit the adipocytes by ___ ___. Carried in blood by ____, released to tissue.
Glycerol is shipped to ___ and converted to glucose by _____.
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