lipid metabolism Flashcards
what are lipids?
heterogenous
water INsoluble
hydrophobic
MAJOR source of energy
what are the common classes of lipids?
fatty acids
triacylglycerol
glycerophospholipid
steroid
sphingoglycolipid
where does lipid digestion begin?
stomach
lipase - what about it
catalyzes the digestion of lipids
it is an acid stable enzyme (therefore it can withstand stomach acid)
lipase mainly targets triacylglycerols
where does emulsification of lipids occur
the duodenum
lipase attaches to fat
the mixing in the gut and action of bile salts allow the breakdown of fat into fatty droplets
smaller fat droplets allow lipase to work more efficiently
what molecules do pancreatic enzymes degrade?
TAG - pancreatic lipase
Cholesterol esters - cholesterol esterase
phospholipids - phospholipase A2, lysophospholipase
Degradation of TAGs
TAG —pancreatic lipase—-> 2-monoacylglycerol
degradation of TAGs releases 2 Fatty Acids (C1 and C3)
Degradation of cholesterol esters
cholesteryl ester –cholesterol esterase–> cholesterol
releases Fatty acids
cholesteryl esterase activity INCREASES with INCREASED presence of bile salts
degradation of phospholipids
phospholipase A2 removes 1 FA (fatty acid) from C2, leaving a lysophospholipid
lysophospholiase removes the FA at C1 leaving a glycerophosphoryl base
phospholipid –phospholipase–> glycerophosphoylcholine
pancreatic enzymes in digestion of lipids
pancreatic enzymes breakdown dietary lipids and also release FAs in the process through hydrolysis reaction
what do bile salts do?
bile salts emulsify large fat droplets into small fat droplets
because there is more “surface area” (because there is more fat droplets spread out) lipase action increases = increased lipid absorption
Hormonal control of lipid digestion in sm. intestine
cholecystokinin (in blood to stomach
secretin (in blood to sm. intestine)
gut endocrine cells secrete both hormones by the stimulation of the presence of dietary lipids
what type of cell absorbs lipids?
intestinal mucosal cells (enterocytes)
what components make up a mixed micelle?
lipids, bile salts, fat soluble vitamins (A,D,E,K)
lipids = 2-monoacylglycerol, long chain FA, cholesterol
what even is a mixed micelle?
a mixed micelle is a disk shaped cluster of amphipathic (both hydrophilic and phobic) lipids.
hydrophobic groups are on the inside of the micelle
hydrophilic groups are on the outside of the micelle
where is the primary site of lipid absorption
brush border membrane of enterocytes
resynthesis of TAGs and cholesteryl esters
the mixture of lipids (mixed micelles) absorbed by the enterocytes are REsynthesized into complex lipids in the ER of the cell
what lipids are resynthesized?
triacylglycerol
cholesteryl ester
in the enterocyte cell, what resynthesized components come together in the chylomicron?
phospholipids, TAGs, Cholesteryl ester
where does the chylomicron go after collecting all these lipids?
to the lymphatic system
what is lipid malabsorption?
fats that are not absorbed in the small intestine pass to our colon - resulting in STEATORRHEA - fatty stools
- blockage of bile salts and blockage of pancreatic juice to sm. intestine
- defective cells
what are chylomicrons
chylomicrons are lipid droplets surrounded by phospholipids, unesterified cholesterol, and apolipoprotein
- these things increase the stability of the droplet
how are chylomicrons secreted?
chylomicrons are released by exocytosis from the enterocytes
they enter the lacteals of the lymphatic vessels of the small intestine villi
what pathway do chylomicrons take?
lymphatic pathway –> blood
in the blood, chylomicrons…
chylomicrons carry around lipid components
the TAG components are drawn off the chylomicron by muscle and fat cells
TAG components are hydrolyzed by lipoprotein lipase and release fatty acids into the tissues
how are dietary lipids used by the tissues
TAGs - lipoprotein breaks it down
- muscle and adipose tissues use it
FAs - taken up by muscle cells and adipocytes
- travel in blood
- produce energy
- stored as TAGs
Glycerol - used by liver to produce glycerol-3-phosphate
what are the two forms of fatty acids in the body
free FAs
Fatty acyl esters in TAGs
What is cool about Free FAs
Free FAs can be oxidized to produce energy in the liver and muscle
structure of FAs
hydrophobic hydrocarbon chain and terminal
hydrophilic carboxyl group
amphipathic molecule
fatty acid esters
more than 90% of FAs in the plasma are FA esters
these FAs esters are contained in circulating lipoprotein particles
How do unesterified (FREE) FAs transported?
in circulation with albumin
Saturation of FAs
single bonds - saturated FAs
double bonds - unsaturated FAs
- cis bonds cause a kink in the FA chain
-this causes FAs to not pack as tightly together
- this leads to lower melting point
- double bonds spaced at 3 carbon intervals (C9, C12, C15)
longer hydrocarbon chain
higher melting point
arachidonic acid
20:4 (5,8,11,14)
20 carbons long
4 C=C bonds between C5-6, C8-9, C11-12, C14-15
what are the 2 essential FAs
linoleic acid - omega 6 FAs
alpha-linolenic acid - omega 3 FAs
what can carbs and proteins be converted into
carbs and proteins can be converted to fatty acids and stored as triacylglycerols
where does FA synthesis usually occur
liver (mainly)
lactating mammary glands
adipose tissue (less)
in cytosol
OVerview of FA synthesis
incorporates carbons from acetyl CoA into the growing FA chain
uses ATP and NADPH
FAs are synthesized by the repetitive addition of 2C units to the growing end of the hydrocarbon chain
acetyl coA has to move from mitochondria to the cytosol
acetyl coA + oxaloacetate -> citrate
citrate crosses membrane to cytosol where its reconverted to oxaloacetate and acetyl CoA
this is the production of cystolic acetyl CoA
where does desaturation of FA occur?
in the smooth ER
what are solid lipids called?
fats
what are liquid lipids called?
oils
what makes up a triacylglycerol
3 molecules of fatty acid esterified to a molecule of glycerol
these 3 molecules of FA will usually be different from each other (one unsaturated, one saturated, one either)
Why can’t TAGs form stable micelles?
they are only slightly soluble in water
their outside is not completely hydrophilic
where are TAGs stored?
they are stored as oily droplets in the cytosol of adipocytes in adipose tissue
these droplets act as a major energy reserve for the body
during TAG synthesis, what is the INITIAL acceptor of FAs
glycerol 3 phosphate
where does this occur?
in the liver
BUUUTTTTT - steps of TAG synthesis also occur in adipose tissue
what form must FAs be in when being converted into TAGs?
FA-CoA form
TAG synthesis
glucose-3-phosphate —FA-CoA—>TAG
whats up with TAGs and the liver?
well, the initial step of TAGsynthesis occurs in the liver
TAGs however, are not mainly stored in the liver as they are stored in the adipose tissue
FA stored in adipose are WHAT
they are the major fuel storage reserve of the body
how much energy does FA oxidation produce?
9 kcal/gram
way more than carbs (4) or proteins (4)
release of FAs from TAGs
initiated by hormone sensitive lipase
this enzyme removes a FA from carbon 1/3 of the TAG
BETA OXIDATION YASSSS
major catabolic pathway for FAs
2 carbon fragments are removed from the carboxyl end of the FA-CoA producing Acetyl CoA, NADH, and FADH2
occurs in the mitochondria
what is the first step to beta oxidation?
LCFA (long chain fatty acid) transported into mitochondria via carnitine shuttle
SCFA (12 carbons or less) can enter mitochondria without carnitine shuttle
2 carbon fragments are removed from carboxyl ends of FA CoA - and what does this produce?
(2 carbon) AcetylCoA, NADH, and FADH2
odd carbon chain beta oxidation
2 carbon Acetyl CoA, NADH, FADH2, AND a 3 carbon Propionyl CoA
propionyl CoA is metabolized into succinyl CoA
Succinyl coA can then ENTER THE KREBs CYCle!!
what is the difference between BO in saturated and unsaturated FAs?
unsaturated FAs provide less energy than saturated FAs
unsaturated FAs require more enzymes to do BO
beta oxidation of VLCFAs (very long chain)
go through preliminary b oxidation in peroxisomes
then they go in the carnitine shuttle and go through normal process
what happens with excess acetyl CoA from beta oxidation in the liver?
acetyl-CoA is converted into ketone bodies!!
this happens if you are intaking A LOT of lipids and LOW carbs
also happens if you are starving - your body will consume fats
diabetes is a part of using ketone bodies for fuel bc of carb catabolism issues
what happens when rate of ketone body formation is greater than their use?
ketone body levels rise in blood (ketonemia) and rise in the urine (ketouria)
seen in type 1 diabetes
FRUITYYYYY odor (acetone)
phospholipidssss YASSS (what are they made of)
they are polar, ionic
composed of alcohol attached to a diacylglycerol or sphingosine
what are the 2 types of phospholipids?
glycerophospholipids (glycerol backbone)
sphingolipids (contain sphingosine)
how are glycerophospholipids formed?
from phosphatidic acid and an alcohol
SIGNIFICANT Sphingophospholipid
sphingomyelin - it is part of the myelin of nerve fibers
where are phospholipids synthesized?
in the Smooth ER girl
what are the two most abundant phospholipids in eukaryotes?
phosphatidylethanolamine and phosphatidylcholine
phosphoglyceride degradation
phospholipases cleave phospholipids at a specific site
degradation of sphingomyelin
use of sphingomyelinase breaks down sphingomyelin and leaves a ceramide
glycolipids - where are they found?
in nerve tissue
what do glycolipids have to do with blood groups
glycolipids are actually a source of blood group antigens and tumor antigens
their carb portion is antigenic
what differentiates sphingomyelin from glycosphingolipids?
sphingomyelin has a phosphate, GSLs don’t
what determines the type of glycosphingolipids?
the amount and type of carbohydrates present
neutral glycosphingolipids
aka cerebrosides
ceramide monosaccharides
has galactose or glucose as the sugar
acidic glycosphingolipids
negatively charged
what are ceramides
sphingosine + fatty acid (FA)
what enzyme is involved in the synthesis of glycosphingolipids?
glycosyl transferase
where does the synthesis of glycosphingolipids occur?
the GOLGI
what enzymes are involved in the degradation of glycosphingolipids
beta-galactosidase
neuraminidase
prostaglandins + eiconasoids origin
polyunsaturated fatty acids with 20 carbons
what do prostaglandins and eiconasoids do?
they are EXtremely potent and exhibit physiologic (inflammatory) and pathologic (hypersensitivity)
