Catabolism of FA Flashcards
what 3 functions does cholesterol serve?
1) membrane structure
2) precursor for bile acids
3) precursor for steroid hormones
what is esterification?
addition of FA to glycerol to form an ester bond
-Formation of fat
explain the structure of a FA
carboxyl group (polar head)
non-polar HC tail
-amphipathic molecule
-can be saturated or unsaturated
what 2 configurations can a FA be found in? which one is the most common and there fore assumed?
trans and cis
-cis is the most common and the db is assumed to be cis unless otherwise stated
how many carbons do you expect short chain, medium chain and long chain FA to have?
short chain <6C
Medium 6-12
long 13-21* primary focus
very long >22
How is the type of omega fat determined?
by the number of carbons away that the first db is from the methyl end
what is conjugation?
1 single bond between each db
how many C is palmatate? what type of FA is it? what is its common name?
16C
-saturated FA
-palmitic acid
what 2 major factors affect MP? which one causing more of an effect?
1) length
2) saturation
-saturation drops MP more (more dramatic affect)
how does increasing length and saturation affect MP of a FA?
longer chains- increases MP
more unsaturation - lower MP
what is a triacylglycerol?
3 fatty acid esters of glycerol
what are white fat cells? what are their primary functions?
Adipocytes
1) storage of fat for energy
2) hormone production
what hormone is released from adipocytes to regulate appetite?
leptin
What is the storage and breakdown of FAT known as
synthesis of TAGs from FA- esterification
Breakdown of TAGs to form FA- lipolysis
What is the synthesis and breakdown of FA known as?
synthesis of FA - FAS
breakdown of FA -beta oxidation
what deterines the amount of fat stored in the body?
1) the rate of the breakdown and synthesis of TAGs
2) fat consumption
what is the affect of glucagon in adipocytes in regards to TAG regulation? what target enzyme does PKA phosphorylate as a result of this signal? what effect does this have on the enzyme?
glucagon stimulates breakdown of TAGs
-hormone-sensitive lipase is phosphorylated, which activates the enzyme
what is the role of hormone sensitive lipase?
1) breaks down the first FA from TAGs to form diacylglycerol
2) Breaks down the 2nd FA from DAG to form monoacylglycerol
what enzyme is needed to convert monoacylglycerol into glycerol + FFA?
monoacylglycerol lipase
what is the most important lipase responsible for breaking down TAGs into diacylglycerols?
Adipose triglyceride lipase
(ATGL)
what happens to majority of the FA produced from the breakdown of TAGs (lipolysis)? what happens to the glycerol?
-majority of the TAGs are released into the blood
-all of the glycerol is released into the blood
what does adrenaline and epinephrine signal in adipocytes?
fight or flight
-energy is needed, stimulates the same pathway as glucagon
what is the function of perilipin? how does phosphorylation / dephosphorylation affect its activity? what phosphorylates it?
unphosphorylated perilipin coats lipid droplets, shielding them from hormone sensitive lipase
-when phosphorylated by PKA it is activated and undergoes conformational changes; the change in structure allows the lipase to access the lipid droplet and break it down
what FA can readily diffuse across the plasma membrane? how is this possible given given the charge of FA at physiological pH?
short / medium chain
-at pH 7 FA are deprotonated and carry a (-), however, once in contact with the membrane they pick up a H+ and can diffuse across
what 2 signals stimiulate FA transporters onto the plasma membrane?
1) insulin
2) contraction
-increases [AMP] –> increases [AMPK]–> stimulates increase in transporter
what transporter do FA transporters act like?
GLUT 4
How are FA transported?
bound to albumin
what 2 things make fat more efficient to store than glycogen? how much moreenergy does fat contain as compared to glycogen?
1) more energy is availbale from FA because they are highly reduced
- electrons from H+ are released to be used in ETC
2) it does not need to be stored with water (anhydrous)
- 1g of fat contains 7x more energy
what are the 2 major sites of FA catabolism? what are the FA used for in each of the sites?
1) liver
-Produces acetyl-coA which can be used to make ATP or ketone bodies
2) skeletal muscle
- Produces acetyl-coA to make ATP during aerobic catabolism
when conditions are ketogenesis increased?
1) starvation
2) diabetes
why is ketogenesis not as prevalent during exercise?
because it is stimulated during hormone driven gluconeogensis
what are the 3 main steps to FA catabolism? where do these processes occur?
1) Activation of FA (cytosol - some in matrix)
2) Transport into mitochondria (matrix)
3) Beta oxidation (matrix)
what bond in coA allows us to form a high energy bond…in turn allowing us to create alot of enegry?
HS group
explain the steps in FA activation? what enzyme catalyzes this rxn? what is needed to activate the FA? how many high energy bonds are in this rxn? what are they)
1) FA attached to a phosphate group which releases pyrophosphatase, creating a mixed anhydride (high energy)
2) attachement of coA and release of AMP to form Acyl-coA
3) pyrophosphatase is then converted to inorgancic phosphate by inorganic pyrophosphatase
- creates energy to drive the rxn forward
-fatty acyl-coA synthetase
-3 types of high energy bonds (phosphoanhydride, mixed anhydride, thioester)
are LCFA , MCFA, and SCFA activated differently?
yes, LCFA are activated in the cytosol and MCFA / SCFA can diffuse across the membrane and are activated in the matrix
what is another name for thiokinase?
fatty acyl-coA synthetase
how many ATP moleucles are required to activate FA? explain why?
2
- Adenylate kinase is needed to reconvert AMP back to ATP to be used in the reaction
list all the enzymes involed in FA activation?
1) thiokinased (FA acyl-coA synthetase)
2) inorganic pyrophosphatase
3) Adenylate kinase
4) ATP synthase
explain the steps in the transfer of activated FA into the mitochondria? what types of FA are transported across this transporter?
1) acyl group transferred to carnitine using carnitine acyl/palmitoyl transferase I (CAT1)
-breaking thioester and forming ester bond
2) carnitine acyl group is taken across IMM with carnitine carrier protein (Carnitine transferase)
3) in the matrix carnitine acyl / palmitoyl transferase II transfers acyl group back to coA
-breaks ester bond
4) free carntine is taken back out
- transfers free FA and LCFA
what type of transporter is carnitine carrier protien (carnitine transferase)?
antiporter
what effects stabilize carnitine? how does this impact the energy released? what type of rxn is it a part of?
solvation effects stabilize carnitine allowing the TRANSESTERIFICATION (breaking and reforming of ester bond) to release a lot of energy
where is CAT1 located? where is CAT2 located?
1) facing the cytosol
2) facing the matrix
where is carnitine from? what occurs with a carnitine deficiency? how woud you treat someone w carnitine deficiency?
1)small amounts synthesized in the cell
2)diet
- FA buildup in the cytosol and an inability to oxidize LCFA (difficulty in energy utilization of dietary FA)–> causes cellular damage
- give them a diet high in short / medium chain FA (no energy needed to get into matrix
what 4 rxns occur every round of beta oxidation?
Oxidation
Hydration
Oxidation
Thiolyses (releases Acetyl coA)
how many Acetyl coA are released every round of beta oxidation? what about the last round?
1 released every round
2 released in the last round
what is the first rxn in beta oxidation? what does it produce?what eznyme is used? what cofactor is involved? why is that cofactor involved and what problem does this create?
oxidation using FAD to create FADH2 by a dehydrogenase; converting an activated FA to a trans delta 2 enoyl coA
-FAD is typically used to generate db, it is a prosthetic group so an ETC is needed to utililze thee-s coming from FADH2
how many proteins is Q a substrate for? name them
5
1) complex 1(NADH-Ubiquinone oxidoreductase)
2) complex 2 (succinate-ubiquinone oxidoreductase)
3) complex 3 (ubiquinol cytochrome c oxidoreductase)
4) 3-phosphate glycerol dehydrogenase
5) ETC-Q oxidoreductase
what bond must the FA be in during the hydration rxn of beta oxidation?
trans delta 2
what occurs during the 2nd rxn of beta oxidation? what enzym is involved? what is needed for this rxn to occur? what does it produce? what is important abt the resulting structure?
hydration with H2O of a trans delta 2 enoyl coA to produce beta-hydroxyacyl-coA (using a hydratase)
-adds an OH to the 3rd carbon (beta C)
what occurs during the 3rd rxn of beta oxidation? what cofactor and enzyme is used? what is produced?
oxidation of beta-hydroxyacyl-coA (beta C) using NAD+ and a dehydrogenase
-produces keto-type structure
what is the last rxn in beta oxidation? what cofactor and enzyme is used? what is produced?
Thiolase uses CoASH to generate an acetyl coA and a FA acyl coA that is 2C shorter
what is released every round of beta oxidation?
1 Acetyl CoA
1NADH
1FADH2
explain how many ATP molecules are made from the complete oxidation of a C16:O FA?
106 ATP
7 rounds of oxidation (C/2 -1)
10 ATP from CAC
7NADH =17.5
7FADH2 = 10.5
2 invested to activate FA
in the very last round of beta oxidationn for even FA, what is produced?
2 Acetyl coA molecules
NADH
FADH2
other than energy from FA and water, what else is released from beta oxidation? why is this important?
glycerol which can be used in gluconeogenesis to make glucose
how does oxidation of a uneven numbered db for unsaturated FA occur? what differs from saturated FA oxidation?
1) oxidation of carbons until db is normal, releasing and Acetyl coA, FADH2 and NADH, per oxidation of 2C
2) once it reaches the db, it is in a cis conformation and uses an isomerase to convert it to trans delta 2 conformation
3) once in the trans delta 2 conformation it continues the oxidation as normal
-since there is already a db present after the isomerase is used, there is 1 less FADH2 produced (one less FADH2 for every db)
how does oxidation of an even numbered db for unsaturated FA occur? what differs from saturated FA oxidation?
1) first 3 rounds (for 18C FA) before the db are normal (acetyl coA + FADH2 +NADH produced every round)
2) in the 4th round, once db is reached, isomerase converts cis bond to trans delta 2, losing the production of FADH2 (NADH + Acetyl coA produced)
3) the FIRST oxidation of the 5th round produces FADH2 as normal, however, after this oxidation the FA is conjugated (hydratase doesn’t like)
4) in round 5 a reductase is needed to reduce two db to one db, using NADH, producing NADP+
-the products of this round are normal (generates NADH, FADH2, and Acetyl CoA)
5) the db created is delta 3, therefore, an isomerase is used to convert it to a trans delta 2
6) last 3 rounds after isomerise are normal (3NADH, 3FADH2, 3Acetyl coA)
what enzyme will handle odd-numbered db in FA?
odd numbered db: isomerase
even numbered db: reductase and isomerase
what enzyme will handle even-numbered db in FA?
reductase and isomerase + NADPH
why is the use of NADPH in beta oxidation considered the same as using NADH? how will this impact NADH counting?
NADPH is usually produced in the cytosol, so in order to regenerate NADPH in the matrix, elctrons from NADH in the matrix are transferred to NADPH using the nicotinamide nucleotide transhydrogenase (NNT)
-the gross NADH production is the same, but the net NADH will be 1 less for every db in an even # unsaturated FA (every NADPH used needs an NADH invested to generate the NADPH)
how do you determine the number of beta oxidation rounds for uneven chain length FA?
C -1 / 2 -1
C17 -> C16 /8 = 8 - 1
=7 rounds
what is generated from the oxidatoin of uneven FA chain lengths at in the final oxidation of C? how does this differ from even chain FA?
instead of 2 acetyl coA, an Acetyl CoA + proponyl coA (3C) is generated
-propoinyl coA is converted to succinyl coA and enters the CAC (can be used in gluconeogenesis becuase it enters after decarboxylation)
Explain how propionyl-coA is converted into succinate:
1) converted to a C3 (propionyl coA) carboxylated to a C4 using ATP and biotin as a cofactor
-similar to PDC (contains 3 domains) except acetyl coA does not regulate / activate it
2) Rearranged from C4 to Succinyl coA
what enzyme does net oxidation of succinyl coA require? why?
cytosolic malic enzyme
-succinyl coA is typically generated in the matrix, in order to have net production, malic enzyme in the cytosol must undergo an oxidative decarboxylation of malate to pyruvate (using NADP+)
-pyruvate can then be oxidized to acetyl coA, enetering the CAC and forming succinyl coA
-succinyl coA from propionyl coA is anapleorotic in nature (regenerated to oxidize acetyl coA better)
draw on the white board the net number of ATP produced from the complete oxidation fo a C17:0 FA
what is the difference between ketone bodies and ketones? what are the 3 examples?
ketones refer to the general funtional group while ketone bodies are molecules used for energy when fat is broken down
- beta hydroxybutyrate, acetoacetate, acetone (very volatile not used as fuel)
How are ketones formed (ketogenesis)? where does this occur?
1) 2 acetyl coA molecules are joined to generate Acetoacetyl-coA
2) HMG-synthase adds a water to generate HMG-coA
3) HMG-coA lyase releases coA molecule to be able to transport the molecules across IMM (can’t easily transfer molecules w coA across membrane) generating the first ketone body: acetoacete
4) Acetoacetate is reduced to beta hydroxybutryate and it is released into the bloodstream
- acetone is generated with very high ketone synthesis
which form of ketone body is most likely to be released from the liver and why?
beta hydroxybutryate
-it has more energy to be used do to it being more reduced
which ketone bodies are used for energy?
acetoacetate
beta hydroxybutryate
acetone is not used as a fuel but is exhailed off the breath
what type of transporter is used for ketone bodies? what does this mean for how its transported? how can this be a physiological impact?
monocarboxylate transporter
-uses H+ to transport
can cause ketoacidosis with high amount of ketone transport, increases pH and reducing bindign affinity of O2 to Hb
what conditions slow CAC and increase gluconeogenesis? how does this impact ketogenesis?
starvation + diabetes + low carb diets
-increases ketogenesis
what enzyme does the liver lack to use ketone bodies for energy?
3-ketoacyl-coA transferase
what must acetoacetate be linked to in order to oxidize it? how is this done?
Acetyl coA
-transfer of coA from succinyl coA to acetoacetat (succinyl coA loses its ability to generate GTP in CAC)
