Lecture 14 - Lipid Metabolism Flashcards
What are the 2 routes of lipid assimilation in mammals?
-Endogenous
-Exogenous
what is endogenous lipid metabolism?
Fatty acids are biosynthesized from excess dietary CARBOHYDRATES and PROTEINS
What is exogenous lipid metabolism?
fatty acids are biosynthesized from dietary lipids
Most dietary lipids are….
triacylglycerols
After food is conducted into the stomach, what happens?
the churning action of the stomach muscles produces a liquefied suspension called CHYME
what is the 1st portion of the small intestine called?
the duodenum
Once chyme enters the duodenum, what happens?
the lipid portion of chyme mixes with bile
bile is produced by what?
the liver
where does chyme mix with bile?
in the small intestine (duodenum)
Once bile is produced by the liver, where is it sent and how?
bile is sent to the SMALL INTESTINE through the BILE DUCT
Along the way from the liver to the bile duct, where does bile flow into on the way?
a blind pouch - the GALLBLADDER
Emulsification occurs when….
bile mixes with lipids to form small lipid droplets
inside the cell, ___ and ___ are formed
triacylglycerols and cholesterol esters
____ are synthesized with ____ to form chylomicron
apolipoproteins are synthesized with phospholipids to form chylomicron
Chlyomicrons leaving the intestinal epithelia enter what?
the lymphatic system
once they enter the bloodstream, what happens to chylomicrons?
the triacylglycerols in chylomicrons are hydrolyzed back to fatty acids and taken into adipocytes (fat cells)
do chylomicrons enter a lymph vessel first or the bloodstream?
they enter the lymph vessels THEN get taken into the bloodstream
Adipocytes are the storage site for ___ in the form of ____
storage site for fatty acids, in the form of triacylglycerols (fatty acids that enter adipocytes reform triacylglycerols)
In the fed state, fatty acid concentration is ___ in the blood
low
In the fasting state, fatty acid concentration can increase by ____ fold of the fed state
increase by 100-fold
As blood glucose _____, the brain triggers the adrenal glands and epinephrine is released
FALLS
What does epinephrine do?
epinephrine can bind to receptors in adipocytes. This causes the hydrolysis of stored triacylglycerols
When epinephrine binds to receptors in adipocytes and causes the hydrolysis of stored triacylglycerols, what is formed?
free fatty acids
What are the 3 steps of fatty acid oxidation?
- Activation
- Transport
- Beta oxidation
What happens in the first step of fatty acid oxidation and where does it take place?
ACTIVATION
fatty acids are converted to acyl-coenzyme-A
occurs in CYTOSOL
What happens in the second step of fatty acid oxidation?
TRANSPORT
Acyl-coA is imported into the mitochondria
What happens in the third step of fatty acid oxidation and where does it take place?
BETA OXIDATION
fatty acyl-coA is converted to acetyl-coA
occurs in the MITOCHONDRIAL MATRIX
can oxidation occur on unsaturated fatty acids?
YES - can occur on both saturated and unsaturated
Fatty acids generally have how many carbons?
14, 16, or 18
The Activation step of fatty acid oxidation is reversible or irreversible?
irreversible. 1st enzyme = rate limiting. slowest step. IRREVERSIBLE
Activation overall converts what to what?
converts fatty acids to coA esters
ACTIVATION is assisted by what?
rapid pyrophosphate hydrolysis
explain how rapid pyrophosphate hydrolysis assists the activation step
pyrophosphate is broken up for coupled energy which will help the reaction go forward
which generates more energy - the hydrolysis of pyrophosphate or ATP?
ATP
The transport step in fatty acid oxidation moves ___ into the ____ and is _____
moves fatty acyl-coA into the mitochondria and is INDIRECT
Why is a carnitine shuttle used to move fatty acyl coA into the mitochondria?
because no transport protein exists for CoA or its ester
Can fatty acylCoA permeate across the cell membrane?
no
fatty acyl-CoA can cross the cell membrane using what as a transporter?
carnitine
What enzyme catalyzes the conversion of fatty acyl-carnitine to fatty acyl-coA?
CATII
(carnitine acyl transferase)
What enzyme catalyzes the conversion of fatty acyl-CoA to a carnitine ester?
CAT1
(carnitine acyl transferase)
Explain the entire process of transport in fatty acid oxidation
- Fatty Acyl-CoA is converted to a carnitine ester by CAT1
- A mitochondrial transport protein catalyzes the exchange of CYTOSOLIC acyl-carnitine for MITOCHONDRIAL carnitine
- CAT2 catalyzes the conversion of fatty acyl-carnitine to fatty acyl-CoA
- Carnitine is recycled back into the cytosol
Does CAT2 catalyze the reverse reaction of CAT1? explain
YES
CAT1 catalyzes the conversion of fatty acyl-CoA to a carnitine ester
CAT2 catalyzes the conversion of fatty acyl carnitine to fatty-acylCoA
Which step of fatty acid metabolism has a similar strategy as the Krebs cycle?
beta oxidation
Beta oxidation~
___ carbons are removed at a time from the chain of a fatty acid
2
what enzyme catalyzes the first step of beta oxidation?
Fatty acyl-CoA dehydrogenase
What enzyme catalyzes the second step of beta oxidation?
hydratase
What enzyme catalyzes the third step of beta oxidation?
Acyl-hydroxyl dehydrogenase
What enzyme catalyzes the fourth step of beta oxidation?
thiolase
Can the steps of beta oxidation be repeated?
YES
What 2 steps of beta oxidation use a DEHYDROGENASE enzyme?
1st and 3rd steps
what 2 electron carries are used in beta oxidation?
Q–>QH2 (ETC compex 2)
NAD+–>NADH
What is the main goal of beta oxidation
to convert fatty acyl coA to Acetyl-CoA
Ancillary enzymes are needed to oxidize what?
unsaturated, very long chain, or other fatty acids
unsaturated fatty acids such as ____ are abundant in mammalian blood
oleate
is oleate a saturated or unsaturated fatty acid?
unsaturated
are saturated or unsaturated fatty acids abundant in mammalian blood? how are they oxidized?
UNSATURATED.
oxidized by a slight modification of the previously mentioned pathway
Oleate undergoes how many rounds of beta oxidation?
3
after 3 rounds of beta oxidation, an intermediate with a ____ double bond ___ to the carbonyl is formed
CIS double bond beta to the carbonyl is formed
This intermediate (w a cis double bond beta to the carbonyl) is a substrate for what?
it is a substrate for an isomerase that converts to TRANS double bonds ALPHA to the carbonyl
are fatty acids one of the 3 major lipids?
NO - it’s a building block of lipids
Fatty acids having ____ or fewer carbons can bypass the cytosolic activation step
8
Fatty acids with 8 or fewer carbons are activated directly where?
in the mitochondrial matrix
Fatty acids with 8 or fewer carbons are ____ independent. Explain
they are cartinine independent because they do not require a transport step to enter the mitochondria
VERY LONG fatty acid chains are partially oxidized where?
in peroxisomes
the long fatty acid chains that are partially oxidized in peroxisomes —- are they substrates of CAT1?
NO.
They are activated within the mitochondria
where are ketone bodies produced?
in the liver
“Ketone bodies are exclusively produced in the liver as a ____ pathway during excess production of _____”
SPILLOVER PATHWAY, during excess production of acetyl-CoA
how is it that excess Acetyl-CoA could be produced?
usually due to excess fatty acid oxidation, OR derived from some amino acids known as ketogenic amino acids
A rise in ketone bodies parallels an increase in blood ____ concentration
FATTY ACID
What is the first ketone body? it reacts with ___ to produce _____
Acetoacetate is the first ketone body.
reacts with NADH to form beta-hydroxybutyrate
both acetoacetate and beta-hydroxybutyrate are transported where and why?
out of the cell because the liver has no reactions that further metabolize either of them
what is the third ketone body?
acetone
when do acetone levels rise in the bloodstream?
from the NONENZYMATIC decarboxylation of acetoacetate
WHERE does the oxidation of ketone bodies occur?
in the mitochondria
in the mitochondria, beta-hydroxybutyrate is oxidized to ______
acetoacetate
what are the 2 pathways of acetoacetate?
-could react with NADH to form beta-hydroxybutyrate
-could nonenzymatically be converted to acetone(release of CO2)
what is the next step of ketone body oxidation in the mitochondria after beta-hydroxybutyrate is oxidized to acetoacetate?
a transferase catalyzed reaction occurs
Aceto-acetyl-CoA is converted into WHAT which can be used WHERE?
Acetoacetyl-CoA is converted to 2 acetyl-CoA molecules which can be oxidized in the Krebs Cycel
many tissues can use ____ for energy
ketone bodies
what 2 organs use ketone bodies for energy?
the heart - very active
the brain - uses ketone bodies in severe starvation
Which organ synthesizes lipase and colipase?
the pancreas
A very high lipase concentration in the blood could be an indicator of what?
pancreatitis
why do we need lipase?
to convert triglycerides to fatty acids to be absorbed
(triglycerides cannot be absorbed by the intestine easily.)
What is considered a healthier lipoprotein and what does it stand for?
HDL
high density lipoprotein
glucose
fatty acid
protein
Of these 3, which provides the most energy upon complete oxidation? (assume same weight of each)
FATTY ACID
WHY do fatty acids provide more energy than proteins or glucose?
fatty acids are very reduced
fatty acids are the main energy source for which type of muscle tissue?
cardiac muscle (the heart)
why can fatty acids not enter the brain?
because of its acidic component (COOH)
can ketone bodies cross the blood-brain barrier?
YES - that’s why theyre an alternative energy source for the brain
where is chyme produced in the body?
the stomach
what are 3 components of chylomicrons?
apoproteins
triglycerides
phospholipids
chylomicrons are utilized to….
transport lipids
why are fatty acids NOT a component in chylomicrons?
because they don’tneed a transporter
are chylomicrons big?
yes
chylomicrons continually shed their _____
lipids
HDL is produced when more or less lipids are shed from chylomicrons?
MORE LIPIDS SHED
in which cells are chylomicron formed?
in epithelial cells of the intestine
does chylomicron carry lipids directly to the serum?
NO—- goes to lymph system and then the serum
fatty acid concentration in the blood is low in the ___ state
fed
the activation step is to convert ___ to ____
fatty acids to acylCoa
Where does beta oxidation happen?
in the mitochondria
does the transport step move free fatty acids into the mitochondria using proteins?
NO.
Acyl-CoA is moved into the mitochondria using proteins
Acyl-CoA is used as a carrier to help fatty acids do what?
be more reactive
what are 3 products of beta oxidation?
FADH2
NADH
Acyl CoA
give 3 examples of ketone bodies
beta-hydroxybutyrate
acetoacetate
acetone
is acetyl-CoA a ketone body?
NO -
could be used to generate a ketone body but it’s not one itself
