biochem lecture 8 pt 1 Flashcards
what is lipid catabolism
how lipids are used as an E source
major functions of fatty acids
formation of cell membranes, role in energy metabolism
major component of lipids
fatty acids
what are fatty acids
long chains of hydrocarbons
2 types of fatty acids
saturated and unsaturated
saturated fatty acids
C-C bonds are all single bonds
unsaturated fatty acids
one or more double bond (C=C)
what are fatty acids
hydrocarbon chains; made up excluisvely of Cs and Hs. C-C bonds form backbones, Hs bonded to Cs
what does double bond present in unsaturated fat cause
causes it to bend or kink
what can kinking affect
membrane fluidity
most abundant dietary lipids
triglycerides
where are triglycerides found
animal and plant foods
what are triglycerides referred to
neutral fat/lipid (cuz its uncharged)
why are triglycerides neutral fat
because they are uncharged
what are triglycerides structure
glycerol backbone (3 C structure), 3 fatty acids attached to backbone via ester linkages
what is an “essential” compound
something an organism cannot synthesize on its own; requires it from exogenous source
2 essential fatty acids
linoleic and linolenic acid
can we synthesize linoleic and linolenic acid on our own
nope; need them from outside sources
where do we primarily get linoleic and linolenic acid
from vegetable sources
what are adipocytes
fatty acids/fats that deposit in certain parts of the body/ specific kinda cell
what kinda tissue due adipocytes form
adipose tissue
functions of adipose tissue
protective cushion around body organs, insulating function underneath skin, highly concentrated store of E
roles of dietary fats
E metabolism, E source, cell membranes
another function of lipids
can be metabolites of lipids; bioactive compounds
example of bioactive lipid
prostaglandin
what are prostaglandins important in
regulation of blood pressure, activation of inflammatory responses, smooth muscle contraction
another important lipid
cholesterol
functions of cholsterol
regulates membrane fluidity, precursor of synthesis of molecules like bile salts, steroid hormones
importance of liver in glucose metabolism
major storage site for glycogen. hormones that regulate catabolic and anabolic glycogen pathways are in liver. basically, liver is important for distribution & storage of carbs
how is liver important for lipid metabolism
important for synthesis of lipoproteins, can synthesize clotting factors, and is where cholesterol biosynthesis occurs.
what are lipoproteins
proteins w/ lipids, important for transport of cholesterol and fats
what is precursor for cholesterol biosynthesis
acetyl CoA
what is cholesterol a precursor of
synthesis of bile salts, steroid hormones like estrogen, progesterone, testosterone
two main functions of lipids
membrane lipids, energy storage form
diff types of membrane lipids
phospholipids, glycolipids, archaeobacterial ether lipids
are membrane lipids polar or nonpolar
polar
what are two categories of lipids
membrane and storage lipids
what are phospholipids
major type of membrane lipids we find in cells
what are what we generally call phospholipids
glycerol phospholipids
describe structure of glycerol phospholipids
three carbon glycerol backbone; ester bonds attaching fatty acids at first 2 positions, and phosphate group on C3, on which is a polar head group (alcohol, etc.)
what are sphingolipids
sphingosine backbone; found in membranes, covering of nerve tissue, myelin sheaths, etc.
what lipids are we primarily focusing on
energy storage lipids –> triglycerides
what else are triglycerides known as
storage lipids or neutral lipids
describe structure of triglycerides
3 C glycerol backbone; fatty acids attached to all 3 positions on glycerol backbone via esterification
why do we call triglycerides neutral lipids
because they have 3 fatty acids attached, not 2 fatty acids and polar head group
what kinda molecules are phospholipids
amphipathic
why are phospholipids amphipathic
cuz they have both polar and nonpolar parts (polar head group)
what are neutral lipids
glycerol backbone w/ 3 fatty acids attached
what is glycerol
a triol
what is triol
3 carbon alcohol
describe triglyceride structure
fatty acids linked to glycerol via ester bonds
are glycerol and fatty acids metabolized in the same ways
nope; different ways
how do we get triglycerides
we can synthesize them or ingest from diet
what kinda bonds in triglycerides
ester bond
what kinda bond is ester bond
covalent bond that joins fatty acids to glycerol backbone
do glycerol and fatty acids have same or diff pathways
diff pathways
what processes occur in cytosol
glycolysis, pentose phosphate pathway, fatty acid synthesis
what happens in mitochondrial matrix
cTCA, ox phos, b-oxidation of fatty acids, ketone body formation
what is an interplay of both cytosolic and mitochondrial compartments
gluconeogenesis, urea synthesis
where does synthesis of fats occur
in cytosol
what 3 ways do cells obtain fatty acid fules
diet, fats stored in cells as lipid droplets, fats synthesized in liver for export to other organs
where are fats stored in lipid droplets
adipocytes/adipose tissue
what kinda molecules are fats
hydrophobic nonpolar molecules
what is needed for fats to be distributed/transported to tissues to undergo breakdown/catabolic processes
need to be transported into chylomicrons
what are chylomicrons
allow for nonpolar fat molecules to travel thru otherwise polar aqueous environment (blood)
how are most products of fat metabolism transported in lymph as
as chylomicrons
what happens when chylomicrons are delivered to the specific tissue
undergo metabolic processing; hydrolytic enzymes will break them down
what does process of hydrolyzing triglycerides entail
separating fatty acids from glycerol backbone
where are hydrolytic enzymes found
some in blood, some intracellular
what 2 pathways are in catabolism of fats
glycerol pathway, fatty acid pathway
before we talk about pathways, what do we need to address
how dietary lipids are processed
what happens when we ingest fats from our diet
lipids pass thru stomach, small intestine
where are bile salts stored
gallbladder
what happens to bile salts when we eat food w/ lots of fats
bile salts will be released from gallblader thru a duct system, into duodenum/upper portion of small intestine (bile salts, gallbladder–> small intestine)
what process do bile salts carry out
emulsification
what is emulsification
separation of triglycerides from each other
does emulsification break covalent bonds
nope, just separate triglycerides
what comes after bile salts do emulsification
intestinal lipases
what are lipases
hydrolytic enzymes; cleaves or separates fatty acids from glycerol backbone
what do intestinal lipases do
degrade the triglycerides
what are we left with after intestinal lipases do their jobs
individual fatty acids and glycerol backbone
what is next step after intestinal lipases
absorption of individual fatty acids and glycerol into intestinal mucosa
what is important for absorption of individual fatty acids
lipoproteins; specific transport systems involving lipoproteins
what happens once these individual fatty acids (derived from triglycerides) are absorbed into intestinal mucosal cells
reassembled into triglycerides
what happens to triglycerides when procesed
degradation and then reassembly
why is degradation and reassembly necessary
important for enabling fatty acids to be more efficiently absorbed into intestinal mucosa
what happens to reassembled triglycerides
packaged into a structure called chylomicron
what are chylomicrons made of
combo of triglycerides, cholesterol, apolipoproteins, other lipids
what is the goal of chylomicrons
to transport fatty acids in form of triglycerides that are housed within chylomicron to the target organs (where they will be used as energy
what happens to fatty acids at target organs
will be used as energy
what is goal of chylomicron
to transport fatty acids (in triglyceride form) to target, where it can be used as energy
what are chylomicrons
what we store lipids in as they are being transported throughout bloodstream in body
what are 2 possibilities where we have fatty acid metabolism going on
muscle, adipocytes
what happens in muscle
major site where b-oxidation of fats takes place
what happens in adipocytes
adipose tissue is where we store triglycerides; can be processed and go thru beta-oxidation in muscles
describe where fats are stored and used
we can store them in adipose tissue; if muscle requires E, some triglycerides can be processed, fatty acids oxidized thru b-oxidation in muscles
then what do chylomicrons do
transport fatty acids to target tissues
what happens to triglycerides once they reach target tissue
undergo further processing
what is lipoprotein lipase
does the same thing as intestinal lipase
what do lipoprotein lipase do to chylomicrons
break htme down to individual fatty acids
what happens to individual fatty acids broken down by chylomicrons
absorbed into myocytes/adipocytes, where they can be oxidized/stored
what happens to fatty acids in myocites
undergo oxidation
what happens to fatty acids in adipocytes
stored in fat droplets
describe chylomicron structure
phospholipid surface, polar head groups facing outward
where do polar head groups face in chylomicrons
face outward
what makes up chylomicrons
major composition is triglycerides
what part of chylomicrons do triglycerides make up
80% of mass
what other lipids in chylomicron
phospholipids, etc.
where is phospholipids on chylomicron
form exterior layer
what is present on surface of chylomicron
apolipoproteins
function of apolipoproteins
trigger activation of some lipases
example of apolipoproteins activating lipases
lipoprotein lipases being triggered one chylomicron reaches destination
what are main functions of apolipoproteins
binding to specific cell surfaces, and activating lipases
what happens to triglycerides once they’ve been reassembled in target tissues
if in muscle tissue (where we’re gonna oxidize fatty acids and glycerol to generate ATP E), two separate pathways
what does glycerol undergo
converted to GAP I(in short multi step pathway), GAP converted to acetyl CoA, acetyl CoA goes to krebs cycle
what happens to the GAP
fed into glycolysis, converted into acetyl CoA
what happens to acetyl CoA
into TCA cycle, carbons get completely oxidized
what convergence do we see w/ glycerol
convergence of glycerol pathway thru formation of GAP in glycolysis pathway
what pathway for fatty acids
beta-oxidization pathway
what do we get after fatty acids go thru b-oxidation
two carbon acetate fragments (from fatty acids, long chain hydrocarbons)
what happens to those 2 carbon acetate fragments
joined w/ coenzyme A to generate acetyl CoA
what happens to acetyl CoA
enter TCA cycle, carbons undergo complete oxidation
where does term B-oxidation come from
from the fact that we generate two carbon fragments; indicates where cleavage rxns are gonna cocur
what can be genrated from oxidation of fats
substantial amount of reducing power
what can we get from acetyl CoA
lot of PE, lot of NADH and FADH2
why can we get a lot of NADH, FADH2
because each of those acetyl CoA units can enter TCA cycle and generate a lot of NADH, FADH2
what happens when triglycerides get degraded
individual fatty acids have been separated from glycerol backbone
what happens to individual fatty acids
beta-oxidation pathway
what happens to glycerol
glycerol pathway
how many steps in glycerol pathway
3 steps
what happens in glycerol pathway
glycerol is converted to glyceraldehyde-3-phosphate (GAP)
what is first step of glycerol pathway
glycerol –> glycerol-3-phosphate
what enzyme for step 1 of glycerol pathway
glycerol kinase
what is second step of glycerol pathway
glycerol-3-phosphate –> dihydroxyacetone phosphate (DHAP)
what enzyme for second step
glycerol-3-phosphate dehydrogenase
what does glycerol-3-phosphate do
generates some reducing power
what is DHAP
glycolysis intermediate; metabolically a dead end
can DHAP undergo further processing
nope
what do we need to do to DHAP
convert it to GAP
what is step 3 of glycerol pathway
dihydroxyacetone phosphate (DHAP) –> glyceraldehyde-3-phosphate (GAP)
what enzyme in step 3 of glycerol pathway
triose phosphate isomerase
is there an energy investment? where
yes, step 1
why does it not matter that we used ATP
cuz we will harvest E thru substrate level phosphorylation in glycolysis, and more from reducing power in TCA cycle
what do lipases do
hydrolyze triglycerides; get fatty acids and glycerol
what happens to fatty acids
form acetyl CoA (thru beta oxidation), go into TCA
what happens to glycerol
glycerol pathway
sum yp glycerol pathway
glycerol is phosphorylated to glycerol-3-phosphate. glycerol-3-phosphate is oxidized to DHAP. DHAP is isomerized to GAP
what happens to GAP
enters glycolysis
what is end product of glycerol pathway and what happens to it
glyceraldehyde-3-phosphate; goes into glycolysis
what happens to GAP after glcyolysis
converted to pyruvic acid
what happens to pyruvic acid at end of glycolysis
converted to acetyl CoA
where does acetyl CoA go
TCA
what is end product of beta oxidation of fatty acids
acetyl CoA
what happens to acetyl CoA
goes into TCA cycle
what is generated in steps where fatty acids converted to acetyl CoA
little bit of reducing power
another word for beta oxidation of fatty acids
fatty acid breakdown (catabolism)
what 3 steps are required for fatty acid breakdown
mobilization, activation & transport, breakdown or beta oxidation
what is first overall step in beta oxidation
mobilization. triglycerols degraded into fatty acids and glycerol, subsequently released from adipose tissue into E-requiring tissues.
what is mobilization step
lipases degrade triglycerides into 2 main components: glycerol backbone, fatty acids. if in adipocytes, glycerol & fatty acids are gonna be released and transferred to tissues that need E (like muscle and liver)
what happens after mobilization step, after fatty acids are absorbed into tissues that require E
need to undergo an activation step, and transportation into mitochondria
what happens once fatty acids are in mitochondrial matrix
undergo step 3, beta oxidation
where does beta oxidation occur
mitochondrial matrix
what is beta oxidation
breakdown of fatty acids
what regulates mobilization of triglycerides
insulin and glucagon
where else were insulin and glucagon
carbon metabolism
what are both epinephrine and glucagon
GPCRs
what do epinephrine and glucagon do
activate adenylyl cyclase
what does adenylyl cyclase do
converts ATP to cAMP
what does cAMP do
activates PKA
what does PKA activate
triacylglycerol lipase
what does triacylgycerol lipase do
responsible for hydrolysis/release of fatty acids from glycerol backbone of triglycerides
what happens once fatty acids released from glycerol backbone
gonna be exported from adipocyte to tissues who need E
what do we have in adipocytes
lipid droplets or concentrations of tryglycerides
what do triglyceride metabolism and glycogen breakdown/synthesis have in common
same hormones
what happens in low blood glucose conditions
we will release of glucagon
what does glucagon do
activates pathway in previous slide (cAMP –> PKA)
what does PKA do
activates hormone sensitive lipase
what does PKA do in adipocytes
phosphorylates a protein called perilipin
where is perilipin
situated on the surface of lipid droplets
basically what happens when glucagon activates PKA
2 things: PKA phosphorylates and activates hormone sensitive lipase, and will phosphorylate perilipin protein on surface of lipid droplet
what does phosphorylating perilipin do
increases accessibility of those triglycerides to hormone sensitive lipase; makes triglycerides more accessible to hormone sensitive lipase
what does hormone sensitive lipase do
hydrolysis of ester bonds that release fatty acids from glycerol backbone
what happens after lipases breakdown tryglicerides
we get transport of fatty acids in bloodstream
how are fatty acids being transported thru blood
serum proteins that can bind to fatty acids; specific lipid binding proteins that can cover and transport hydrophobic lipids
why doesn’t this transport involve chylomicrons
cuz chylomicrons are in processing of dietary lipids, not mobilization
what do serum proteins do
glom onto fatty acids, transport them
where are fatty acids going
to myocyte; to be fully utilized by b-oxidation
example of serum protein
albumin
what do serum proteins do
bind to fatty acids, important for their transport thru bloodstream
basically sum up mobilizatoin
mobilize triglycerides from fat stores in adipose tissue, transport fatty acids where they can be taken up into myocytes into muscle cells for beta oxidation
what do hormone sensitive lipases do
cleave these ester linkages
what are gonna be products of hormone sensitive lipases
individual fatty acids, glycerol backbone
why are they called hormone sensitive lipases
because pathways are activated by these hormones
what effect do insulin and glucagon have on these lipases
opposing effects
what does insulin do to hormone sensitive lipase
inactivates lipase
what does glucagon do to hormone sensitive lipase
activates it
sum up overall effects of these lipases in presence of hormones
inhibitory in presence of insulin, stimulatory in presence of glucagon
