Week 11- Unit 3 Flashcards
The emulsified micelles containing, bile acids, monoglycerols, free fatty acids and cholesterol interact with the intestinal wall and are trasported in the blood in _______.
Cholymicrons
Cholymicrons function to transports DIETARY ______ and ____ to the peripheral tissues.
lipids
cholesterol
_____ and ______ are associated with cholymicrons and are integral for the functionality of these lipoproteins.
ApoB48
ApoCII
After the lingual and gastric lipases digest the dietary triacylglycerols, _______ will emulsify the triglycerols, then ____ and ____ will break down the Triglycerols in the small intestine.
Bile salts
Pancreatic lipase
Colipase
What does the action of pancreatic lipase and colipase do to the TG?
Breaks the TG into Free fatty acids and Monoacylglycerols (2-MG) in the small intestine
What does the Micelle form do ?
facilitate the movement of FA and Monoacyglycerols into the intestinal epithelium
What composes a Triglyceride?
Glycerol unit (3-C chain with hydrogens) 3 Fatty Acid Chains (Hydrocarbon chain)
Bile salts are _______ compounds synthesized in the liver from _______. They act as detergents and bind to the fat.
Amphipathic (both hydrophilic and phobic properties)
Cholesterol
Bile salts act as detergents that increase the _____ _____ of the Fats so that they are broken down easier during peristalsis action.
surface area
Where is Pancreatic lipase and Colipase made?
Secreted from pancreas
Pancreatic lipase and Colipase is secreted from the pancrease in response to the hormone _______.
Cholecystokinin
At the same time Cholecystokinin is signaling to the pancreas , ______ (hormone) signals the release of ________.
Secretin
Bicarbonate
What does the release of Bicarbonate into the intestine by Secretin do ?
increases intestinal pH to about 6 - more amenable to enzyme activity
Initially , coating of bile salts ______ pancreatic lipase.
inhibits
Colipase will bind to dietary fats and ______ the inhibition that the coating of bile salts causes on the action of pancreatic lipase.
relieve
Once Colipase binds to dietary fats and the inhibition on pancreatic lipase is relieved, the Pancreatic lipase will digest dietary fats through _______.
Hydrolysis (into FA+Monoglycerol)
What is the product of digestion of a trigyceride by Pancreatic lipase and Colipase?
2 Free Fatty Acids
2-Monoacyglycerol
Micelles are packages that will contain what 4 things?
Cholesterol
Phospholipids
FFA
Monoacylglycerides
Micelles are again emulsified by ______ _____.
Bile salts
More than ___ of Bile salts are reabsorbed. They travel through the ______ circulation and return to the liver and redeposited in the gall bladder.
95%
Enterohepatic
The micelle will interact with the ___ ____ villae. They can then diffuse into the intracellular space of the intestinal epithelial cells.
Brush Border
After diffusion of lipid molecules enter the intestinal epithelial cells, where do they go first and what happens?
Smoooth ER
-FFA are repackaged into Triglycerides for transport in Cholymicrons
In the Smooth ER of the intestinal cell, the FFA is combined with ATP to make FA-AMP and then interacts with what to make what product?
interacts with CoAsh
Product is FA-CoA
and AMP is release in creation of product
What is the purpose of the FA-CoA?
It will create a condensation reaction acting on the 2-Monoacylglycerol (releasing CoAsh used as energy) to make:
Diacylglycerol
What happens after Diacyglycerol is made in Smooth ER?
FA-CoA acts again on it and creates the :
Triacylglycerol molecule
Chylomicron are composed of ?
Cholesterol in monolayer/cholesterol ester
Peripheral apoprotein
Apoprotein B48
Core of mainly non-polar lipids
Triacylgylerols
Monolayer of mainly amphipathic lipids (NOT Phospholipid BILAYER)
Cholesterol Ester is a molecule that has been esterified by a ______ _____ chain.
Fatty acid chain
-keeps cholesterol in the hydrophobic core instead of the membrane of Cholymicron
What is the largest component of a Chylomicron?
Triglycerides
Chylomicrons are largest of lipoprotein molecules
What is the smallest component of a Chylomicron?
Cholesterol
Where does ApoB-48 come from ?
Rough ER
Where does the ApoB-48 and synthesized Trigycerides interact to create the Nascent Chylomicron?
Golgi Complex
What enzyme is acting with ApoB-48 and Lipids and Triglycerides to form a larger and larger ApoB particle that goes to the Golgi for maturation and secretion as nascent chylomicron?
MTP or MTTP
-Microsomal Trigyceride Transfer Protein
(in the RER)- forming the phospholipid membrane too
What is the Nascent Chylomicron secreted into?
Chyme then carried Lymph and then enter blood through thoracic duct
In the maturation of the nascent Chylomicron to a mature chylomicron , where does it occur? what does it interact with that will drop off the 2 Apo proteins it needs?
In the blood
Interacts with HDL which is smaller and transfers its ApoCII and ApoE onto Chylomicron (essential for its function)
In B-Apoprotein genes , they are translated into different proteins using what process?
mRNA editing (single nucleotide is changed) -where a stop codon is introduced in a certain area to make different proteins (length of AA chain determines protein type ApoB-100 vs ApoB-48 for example)
In the liver the B-Apoprotein gene is transcribed then translated fully to create the ApoB 100 protein for use, true or false?
True
Where is the B-Apoprotein gene a subject of mRNA editing to make ApoB-48 that is needed for digestion?
the intestine (shorter protein than the one created in liver) - truncated protein
What are the two Apo proteins that are required by Nascent chylomicron for maturation that are trasferred by HDL?
ApoCII
ApoE
(both donated by HDL in the Blood)
ApoCII is required on the Chylomicron for interaction with what protein?
Lipoprotein Lipase
what does Lipoprotein lipase do in the blood?
hydrolyses the Triglycerides in the blood into FA +Glycerol
What is the purpose of the lipoprotein lipase hydrolyzing the Trigycerides in the mature Chylomicron in the blood?
FFA become available in the blood for uptake by either the Muscles or Adipose tissue
What will the muscle use FFA for ?
Beta oxidation - generate energy
What will the adipose do with FFA?
repackage them as Triglycerides as fuel storage
What is Chylomicron called once it has delivered its Triglycerides in the blood to the lipoprotein lipase for breakdown?
Chylomicron remnant-
What is chylomicron remnant taken up by (present in blood) ?
what receptor on liver interacts to uptake it?
liver
ApoE receptors
Once the Chylomicron remnant is taken up in liver, what happens to it?
in liver as endocytic vesicle that is digested by Lysosomes
-then any extra FA, Cholesterol, AA or Glycerol is metabolized by liver
In Chylomicron assembly which Aop Protein is transferred from HDL?
a. ApoB100
b. ApoB48
c. ApoCII
d. Apo A
ApoCII
What is the significance of ApoB-48 ?
Designates something as a Chylomicron
-unique to chylomicrons
How do insulin levels impact the transport of dietary TG?
- after meal Insulin is often elevated
- Insulin impacts process through Lipoprotein lipase activity by increasing its activity and increasing upatke of FFA in Adipose and Muscle
Nascent chylomicrons interact with HDL particles and obtain what Apo Proteins?
ApoCII
ApoE
Fatty acid synthesis takes place in the _______ in the _____ of cells.
Liver
Cytosol
Fatty acid synthesis requires what two things?
AcetylCoA
NADPH
Where does the NADPH come from that is required for Fatty acid synthesis?
PPP and Malate Dehydrogenase reaction
AcetylCoA is generated in the mitochondria, it is then shuttled out as _____.
citrate- once in cytosol it is converted back to acetylCoA
VLDL stands for ?
Very Low Density Lipoproteins
How are fatty acids synthesized in the liver transported to the adipose for storage?
through action of VLDL particles - packaged and released from liver
What do the VLDL that is released from liver contain for Apo protein?
ApoB100 and ApoCII
What does VLDL interact with to hydrolyze the FA into stored TG?
LPL- Lipoprotein lipase on the capillaries (Chylomicrons interact with LPL too)
Beta Oxidation of Fatty Acids takes place in ?
Mitochondria under low energy conditions
The oxidation of Fatty acids in beta oxidation in the mitochondria will produce what that is accepted by the ETC?
AcetylCoA
NADH
Under certain conditions, the acetylCoA snythesized from beta oxidation can be used to synthesize _____.
Ketones
If blood glucose is high: insulin is high what is FA synthesis? what is TG synthesis? What is liver glycolysis?
FA synthesis is high
TG synthesis is high
Liver Glycolysis is high
If blood glucose is low: glucagon is high What is Gluconeogenisis? What is Lipolysis What is liver glycolysis ?
Gluconeogenesis is high
Lipolysis is high
Liver Glycolysis is low
In the liver:
after pyruvate is converted to AcetylCoA in the mitochondria it will interact with what to make what?
OAA to make Citrate
After Citrate is synthesized in the mitochondria, it can be transported out in to the cytosol of liver cell and then what happens?
OAA is removed from Citrate and it is converted back into AcetylCoA
What happens when you get AcetylCoA back in the liver cytosol during FA synthesis?
It interacts with Acetyl CoA carboxylase to make:
Malonyl CoA
What does the Malonyl CoA do in Fatty acid synthesis?
it interacts with the Fatty acid synthase which will combine with NADPH (releasing NADP+) to create Palmitate
What is the product of the Fatty acid synthase in the liver ?
Palmitate (C-16 Fatty acid)
What is the GLUT transporter in liver cells that uptakes Glucose at the beginning of FA synthesis?
GLUT 2
What happens to the Palmitate after made?
Activated to a Fatty AcylCoA
What is the next step after the creation of Fatty AcylCoAs from Palmitate?
3 Fatty AcylCoA will interact with 1 Glycerol 3-Phosphate
-Creates Triacylglycerol
What happens to the Triacylglycerol once created in liver cells during FA synthesis?
packaged with Apo-proteins, other lipids (phospholipids, cholesterol)
-creates a VLDL to be secreted into the blood
Where does the AcetylCoA for FA synthesis in liver come from ?
Oxidation of Glucose
Where does the NADPH come from that is used in FA synthesis in the liver?
PPP
Malate Dehydrogenase
Elevated AcetylCoA will inhibit _____ and stimulate ______. Reciprocal regulation that facilitates citrate shuttling into the cytosol.
Pyruvate Dehydrogenase (makes AcetylCoA)
Pyruvate Carboxylase (makes OAA)
What is the name of the enzyme that will cleave OAA from Citrate once it is in the cytosol to make AcetylCoA for FA synthesis in the liver?
Citrate Lyase
What happens to the OAA after it is cleaved from Citrate in the liver cell cytosol?
It will interact with Cytosolic malate dehydrogenase enzyme and the energy from NADH (leaves as NAD+) to make Malate
What happens after malate is made from the NADH+Cytosolic malate dehydrogenase acting on OAA?
The Malic Enzyme will act on Malate in combination with NADP+
- CO2 and NADPH is release
- Pyruvate is created
What does malate convert to ?
Pyruvate
-byproducts of NADPH and CO2 created as well
Insulin stimulates what two enzymes that are used in the cleavage cycle of Citrate to AcetylCoA in the cytosol ?
- Malic enzyme
2. Citrate Lyase
In the conversion of AcetylCoA to Malonyl CoA is done by what enzyme?
Acetyl CoA carboxylase
What does the enzyme Acetyl CoA carboxylase require for acting on Acetyl CoA to make Malonyl CoA
Biotin
CO2
ATP (energy used and leaves as ADP+Pi)
What is rate limiting step of FA synthesis in the liver?
AcetylCoA carboxylase
highly regulated
What 3 ways is Acetyl CoA carboxylase regulated ?
- Phosphorylation
- Allosteric modification
- Repression or induction of synthesis
Where is the Acetyl CoA first attached to the FA synthase ?
Sulfhydryl group
-Phosphopantetheinyl Sulfhydryl Group
What is the second sulfhydryl group that the initial AcetylCoA is transferred to after it initial attaches to Phosphopantetheinyl Sulfhydryl Group ?
cysteinyl sulfhydryl group
What are the two sulfhydryl groups on the FA synthase?
- Phosphopantetheinyl Sulfhydryl Group
2. Cysteinyl sulfhydryl
What is the purpose of transferring the Acetyl CoA group to the Cysteinyl Sulfhydryl Group?
Frees up the Phosphopantetheinyl sulfhydryl group
Then Malonyl CoA can attach to it on the FA synthase
What happens when both the Acetyl CoA and the Malonyl CoA groups are attached to the Sulfhydryl groups on the FA synthase ?
condensation reaction - allows for transfer of Acetyl CoA onto the Malonyl CoA group (starts elongation of FA chain)
What happens after the Acetyl CoA and the Malonyl CoA are combined, what part of the Malonyl is released as what?
Carboxyl group (COO-) is released as CO2
What is a keto group?
C=O
What is an example of an alcohol group?
H-C-OH
in the first NADPH requiring reaction in FA synthesis, what does the NADPH do ?
It will reduce the Keto group (C=) originally from the AcetylCoA to an Alcohol (HCOH)
What happens after the first NADPH requiring reaction where the Keto group is reduced to an Alcohol ?
Dehydration reaction where the Alcohol (HCOH) next to the CH2 loses H2O to form double bond HC=CH
What is the second NADPH requiring recaction and what does the NADPH do to the presently double bonded HC=CH ?
NADPH will reduce the double bond to form the elongated fatty acid chain (O=C-CH2-CH2-CH3)
What happens to the elongated Fatty Acid chain after the second NADPH requiring reaction?
It can be transferred back to the Cysteinyl Sulfhydryl Group, then allowing new Acetyl CoA to join the free
Phosphopantetheinyl sulfhydryl group so process can repeat until Palmitate (C16) is created
Where is Palmitate elongated or saturated ?
ER
In Desaturation of Palmitate (C16), what are the 4 things that are required?
Oxygen
NADH
Cytochrome b5
Cytochrome reductase (FADH2)
During desaturation of plamitate, the ______ will reduce Cytochrome b reductase (carrying _____).
NADH
FAD+
The Cytochrome b reductase (FADH2) in the desatruation of Palmitate will reduce what?
Cytochrome b5 (Fe2+)
What happens in desaturation of palmitate after the Cytochrome b 5 is reduced?
Interaction with Fatty Acyl CoA desaturase
- O2 and 2H+ are added in the mix
- 2H2O is released
What is the enzyme that will release the 2H2O and create monosaturated fatty acyl CoA?
Fatty Acyl CoA desaturase
What is the difference between the Saturated Fatty Acyl CoA and the Monosaturated Fatty Acyl CoA ?
Saturated has single bonds between Carbons
Monosaturated has one double bond between Carbons
When can Palmitate be elongated?
After activation to palmitoyl CoA
What is required for elongation of Palmitate (C16)?
Malonyl CoA and NADPH
In elongation of Palmitate, the major reaction is the production of _________ (C18)
Stearyl-CoA (similar to fatty acid synthesis)
In desaturation what is being oxidized ?
NADH
Saturated Fatty Acyl CoA
The process of elongation or desaturation can take place with synthesized FA and _____ FA.
Dietary
What is the example of a dietary FA that elongation and saturation can take place upon (essential FA)?
Linoleoyl CoA (polysaturated and called Omega 6)
What will Linoleoyl CoA (Linoleic Acid-Omega 6) be converted to through elongation and desaturation?
What is that FA used for ?
Arachidonoyl CoA
used in prostaglandin synthesis
What is the substance that is added during the process of FA elongation?
Malonyl CoA (ex: Linoleic Acid elongation)
What are the general inputs and outputs during desaturation?
Input:
02+NADH+H
Output:
2H2O +NAD
(FA is oxidized)
PPP and the conversion of Malate to Pyruvate will create?
NADPH
What is the primary regulatory enzyme for FA synthesis in cytosol?
Acetyl CoA carboxylase
How is Acetyl CoA regulated?
Through Phosphorlyation and dephosphorylation
What is an activator of Acetyl CoA carboxylase?
Citrate
What is an inhibitor of Acetyl CoA carboxylase ?
Palmitoyl CoA
What happens when insulin levels are high to the Acetyl CoA Carboxylase?
High insulin levels will activate Phosphatase
-this will remove any phosphate from Acetyl CoA and activate it
What enzyme will inactivate the Acetyl-CoA carboxylase?
AMP-activated protein kinase
-takes P from ATP to add to Acetyl CoA to inactivate it
When will Acetyl-CoA carboxylase be inactivated?
when AMP is high (low energy levels)
-more beta oxidation needs to occur in mitochondria
During FA synthesis, what product will play a role in inhibiting beta oxidation while FA synthesis is occuring?
Malonyl CoA
When FA synthase is active, Malonyl CoA in cytosol will inhibit ________.
Carnitine Palmitoyltransferase I
What is the purpose of inhibiting Carnitine Palmitoyltranferase I that is in the membrane of the mitochondria?
Prevents Beta Oxidation from occuring at the same time as FA synthesis
Regulation of Acetyl CoA carboxylase takes place on several levels. When glucose is low, it will be ________ and ______.
phosphorylated
inactive
What enzyme does the adipose tissue lack the the liver has that effects how you can get Glycerol-3 Phosphate ?
Liver has Glycerol Kinase
Adipose does not
In the liver tissue, Glycerol kinase is important for creating Glycerol 3-P from.________ of _______.
Phosphorylation of Glycerol (only in liver)
In the adipose, what is the only way to make Glycerol 3-P?
Through glycolysis
Once the Glycerol 3-P is present , it reacts with ______ to form ________.
2 Fatty Acyl CoA’s
Phosphatidic Acid
What happens to the phosphatidic acid in the FA synthesis pathway?
It is dephosphorylated to create Diacylglycerol
What happens to the Diacylglycerol in the FA synthesis pathway?
After the Phosphate was removed then Diacylglycerol has a spot free
- 1 Fatty Acyl CoA attaches
- Forms Triacylglycerol (final product to be stored or exported in VLDL)
Synthesis of VLDL particles takes place in the ______ and starts in the rough ____.
Liver
ER
the VLDL is packaged in the ______ with the TG particles.
Golgi
VLDL have a total percent TG _____ ____ a Chylomicron.
less than
Protein concentration and Cholesterol level is ______ in VLDL as compared to Chylomicrons.
elevated
VLDL has a phospholipid _______ and are _____ than chylomicrons.
monolayer
smaller
The VLDL particles in the blood interact with ______ via the Apo protein _______ to hydrolyse TG into FA+Glycerol.
LPL (lipoprotein lipase)
ApoCII
The FA that are released in the blood after interaction of VLDL with LPL will do what in the muscle vs. adipose?
Muscle: Oxidized
Adipose: Recombined to form TG
What happens to the Glycerol that is released in the hydrolyzation of VLDL particles with LPL interaction in the blood?
Glycerol will be transported back to the liver
During the fed state, glucose uptake by the adipose will increase, which will then increase _____ ______ production that is necessary for the backbone of TG.
Glycerol 3-Phosphate
Insulin stimulates the activation of ______ ________.
Lipoprotein Lipase
Once the FA and Glycerol are removed from the VLDL, it becomes ?
and then matures to ?
Intermediate Density Lipoprotein (IDL)
Low Density Lipoprotein (LDL)
LDL will retain what Apo Protein that is necessary for its function? (cholesterol synthesis)
ApoB100
Adipose can function as a _____ organ that releases hormones that impacts how you utilize fuels.
endocrine
Adipose cells involve what two main hormones?
Leptin
Adiponectin
Leptin is released from the adipose tissue as _______ _____.
TG increases
______ signals through Jak-STAT receptor in the hypothalamus.
Leptin
What hormone signals the cessation of eating?
Leptin on the Hypothalamus
What does Leptin insensitivity do ?
still released, but not recognized
- contributes to obesity
- cessation of eating not instigated
Adiponectin release _______ as the adipocyte gets _____.
decreases
larger
Adiponectin activates ______ in skeletal muscle and liver. This will do what?
AMP-Kinase
Increase fatty acid beta oxidation (the Acetyl-CoA carboxylase is phosphorylated and inhibited by AMP kinase)
What does activation of AMP-kinase do ?
inhibits FA synthesis
activates Beta oxidation
In the case of obese individuals , it _____ the release of Adiponectin. This leads to the decrease in _____ of Fatty acids.
decreases
What happens if release of Adiponectin is decreased and less oxidation of FA occurs?
Contributes to elevated Free Fatty Acids in the blood of obese individuals
When the liver converts excess glucose into fatty acids (insulin is high):
Cytosolic acetyl CoA is converted to palmitate and the OAA is converted to pyruvate. True or False?
True
When the liver converts excess glucose into fatty acids (insulin is high):
VLDL particles are synthesized in the liver. True or False?
True - due to TG be synthesized in liver from the new FFA
In high levels of glucose, (high insulin), acetyl CoA and OAA form citrate that leaves the mitochondria. True or False?
True
Under high levels of insulin, pyruvate dehydrogenase is dephosphorylated (activated- makes acetyl coA)?
True
_____ can be a primary carrier for Fatty Acids (C16 Palmitate) in the blood.
Albumin
The FA in blood can diffuse into the cells across the plasma membrane. true or false?
true
In step one of Beta Oxidation, what must happen to the Fatty Acid (C16) for the cell to utilize it?
must be converted to Fatty Acyl CoA
- ATP used to attach CoA
- occurs in cytosol
Fatty Acyl CoA is in the cytosol and ready to be transported into the mitochondria for _____ _____.
Beta oxidation
The transfer of Fatty Acyl CoA into the mitochondria requires what two transport proteins ?
Carnitine palmitoyltransferase I and II
what do the transporters that get the Fatty Acyl CoA into the mitochondria require?
What reaction will occur?
Carnitine
- reaction where Carnitine is attached to the Fatty Acyl CoA as the CoA is released
- Forms Fatty Acyl Carnitine
What happens after the Fatty Acyl Carnitine is created?
it enters the mitochondrial matrix and CoA is reattached as the Carnitine is realsed
-Forms Fatty AcylCoA again
Beta Oxidation will act on what molecule?
Fatty Acyl CoA
4 step process that results in remnant of Acetyl CoA
Beta Oxidation requires ______ and will happen under aerobic conditions.
oxygen
The acetyl CoA created by Beta Oxidation can enter the ______ cycle or it can be used to synthesize ______.
TCA
Ketone bodies
In the conversion of FA to FA-CoA, ATP will contribute a high energy _____ to first make an enzyme bound _______ that will free a _______.
AMP
Fatty Acyl-AMP
Pyrophosphate
The Fatty Acyl-AMP will then use the energy from AMP release to add _____ and make _____.
CoA
Fatty Acyl-CoA
What is the enzyme that facilitates the creation of FA to FA-AMP to FA-CoA?
Fatty Acyl CoA Synthetase (located in many tissues and subcellular locations)
Aceylation of FA to FA-CoA is necessary for utilization for Beta oxidation or synthesis, true or false?
true
To get Fatty Acyl-CoA accross the outer MT membrane, ________ will transport it into the intermembrane space.
Translocase
Once the FA-CoA is in the intermmebrane (cytosolic space) of MT membranes, what will occur?
Carnitine Palmitoyltransferase I (CPT I) will act on it adding the Carnitine and releasing the CoA
-converted to Fatty Acylcarnitine
What happens to the Fatty Acylcarnitine to get it accross the inner MT membrane?
Carnitine Acylcarnitine translocase will transport it across the inner MT membrane (also can transport the Carnitine back into the cytosolic space)
Once the Fatty Acylcarnitine is in the Matrix of the MT, what happens?
Carnitine Palmitoyltransferase II (CPT II) will act on it to release the Carnitine and then re-add the CoA to make :
Fatty Acyl-CoA - used in beta oxidation
The CPT I and II are only required for the transport of ____ ____ FA and not what?
long chain FA
not for short chain or medium chain FA that can move more freely across membrane
In step one of Beta Oxidation, what enzyme will facilitate the transfer of 2H to the FAD to make FAD(2H)?
Acetyl CoA- dehydrogenase
In step one of Beta oxidation, where does the two H come from that AcetylCoA - Dehydrogenase will take?
The Beta and Alpha Carbons on Fatty Acyl-CoA
(alpha-#1 C next to CoA)
(beta-#2 C next to CoA)
What happens to the FA-CoA once Acetyl CoA dehydrogenase acts on it?
Double bond is formed (2H is removed) between alpha and beta Carbons
In step two of beta oxidation, _____ is added across the double bond of alpha and beta carbons.
H2O
What happens when H2O is added across the double bond during beta oxidation?
Beta carbon: Hydroxyl group added (OH)
Alpha carbon: Hydrogen added
What is the enzyme that will add the H2O to the double bond of FA-CoA in beta oxidation?
Enoyl CoA Hydratase
What happens after the beta carbon has a hydroxyl group added and the alpha carbon has a hydrogen added?
The OH on the beta Carbon is changed to a keto group (O=C) and electron from the beta carbon is transferred to NAD to make NADH
What enzyme will create the keto group on the Beta Carbon and transfer the electrons to the NAD to make NADH?
Beta-Hydroxy acyl-CoA dehydrogenase
What happens in the fourth step of beta oxidation after the NADH was created in the previous step?
The bond between the Beta and Alpha Carbons is cleaved with the addition of CoASH
What is the enzyme that will cleave the beta and alpha carbons and add CoASH?
Beta-Keto thiolase
What happens after CoASH is added and the B-Keto Acyl CoA is cleaved ?
creates Fatty Acyl CoA + Acetyl CoA
-FA-CoA is recycled back to top of cycle again until the entire chain is oxidized
There are ____ different types of Acyl CoA Dehydrogenases that depend on the length of the FA chain.and oxidize
4
- short
- medium
- long
- very long
In Omega Oxidation , FA can be oxidized at the _____ carbon of the chain. In the first step the Methyl group (CH3) is oxidized to a ______ group.
Omega
Alcohol (HO-CH2)
The alcohol in omega oxidation is converted to a ________ acid by _______.
Carboxylic
Dehydrogenases (the hydrogen is removed from the alcohol)
The Dicarboxylic acid in omega oxidation can undergo ______ to produce soluable acids that can be excreted in the urine. This is clinically relevant.
Beta Oxidation
Why is the excretion of soluable acids after beta oxidation of the dicarboxylic acid on a Omega C or FA clinically relevant?
Presence of Dicarboxylic acids in urine can be suggestive of deficiencies in beta oxidation
The process of Omega oxidation is not regulated by feedback inhibition. True or false?
True
The Omega oxidation pathway is primarily ________, and is primary active to reduce the level of insoluable FA in the cell .
microsomal
If FA Beta oxidation is not occuring , and FA levels in the cell are elevated, then ______ ______ would be increased and you would find ______ in the urine.
Omega oxidation
Dicarboxylic acids
What is the mechanism to release the Triacylglycerols in the Adipose tissue into FA for export to liver and skeletal muscle for oxidation ?
- Glucagon binds receptor, increases cAMP
- Protein kinase A activated
- the kinase will activate Protein sensitive Lipase
The protein sensitive Lipase in the Adipose tissue is ______ when it is phosphorylated.
Active
What will Lipase break TG into?
3 FA
1 Glycerol
all for export out of the adipose
Beta oxidation is a _____ energy yielding process.
High
What can inhibit Beta oxidation (energy level function)?
as energy increases in form of NADH and FAD(2H)
-these inhibit Beta oxidation
What will inhibit beta oxidation process by inhibiting Fatty Acyl CoA transport into the mitochondria?
what transporter is inhibited?
Malonyl CoA ( from FA synthesis)
CPT 1
AMP-Kinase (muscle, liver) will regulate using phosphorylation of ______ _______ to inhibit it from continuing the FA synthesis process.
Acetyl CoA Carboxylase
-the kinase is active under low energy levels , allows for beta oxidation
True or False:
In the fed state, insulin inhibits the release of FFA from adipose tissue and therefore limits substrate for Beta-oxidation.
True
True or False:
In the fed state, insulin will cause dephosphorylation and activation of acetyl CoA carboxylase that produces malonyl CoA, an inhibitor of CPT 1?
True
True or False:
If the ATP/ADP ration is low, AMP dependent protein kinase will phosphorylate and inactivate acetyl CoA carboxylase
True
True or False:
IN the fasting state, the low insulin to glucagon ratio will result in the decrease of Malonyl CoA and activation of CPT 1?
True
True or False:
In the fasting state, lipolysis is inhibited by phosphorylation of hormone sensitive lipase
False
- Phosphorylation of the hormone sensitive lipase will ACTIVATE
- allows it to free FFA and glycerols from TG
What two forms of Ketones can Acetyl CoA be used to generate? (starvation, pathalogical states)
Acetoacetate
Beta-Hydroxybutyrate
What are the two main Ketone bodies that can circulate and be used as a fuel source?
Acetoacetate
Beta-Hydroxybutyrate
Skeletal muscle can use the 2 Ketone body types in what way?
reconverting to Acetyl-CoA then using for energy
When will the brain use ketone bodies for energy?
extreme starvation conditions
In ketone produciton, when Acetyl CoA levels are especially high ____ will condense 2 molecules of Acetyl CoA to make ______.
thiolase (normally cleavage of FA-CoA chain)
Acetoacetyl CoA (unfavored and only happens if Acetyl CoA levels are very high to force the reaction)
In ketone synthesis , Acetoacetyl CoA will react with _______ to form ______.
Acetyl CoA
3-Hydroxy-3Methyl glutaryl CoA (HMG CoA)
What is the enzyme that facilitates the reaction of Acetoacetyl CoA with another acetyl coA to create 3-hydroxy-3methyl glutaryl CoA?
Where does the energy come from?
HMG CoA synthase
thioester bond from Acetyl CoA
-CoASH is released
HMG CoA (intermediate in Ketone synthesis) is also used in what other synthesis process?
Cholesterol synthesis
What is the next enzyme used after HMG CoA Synthase?
HMG CoA Lyase
What does HMG CoA lyase do ?
Cleaves the HMG-CoA into:
Acetoacetate +Acetyl CoA(released)
True or False:
Acetoacetate from ketone synthesis can not enter the blood directly?
False- it can enter the blood directly
What are the two optional fates of Acetoacetate in ketone synthesis?
enter blood directly
converted to Beta-hydroxybutyrate
The conversion of Acetoaceate to Beta-hydroxybutyrate is normally at _______.
equilibrium
What drives the conversion of Acetoacetate to Beta-hydroxybutyrate conversion in the cell?
Ratio of NADH to NAD
-when NADH is high, it will make more Beta-Hydroxybutyrate , when low then direction will reverse
Acetoacetate can spontaneously be _______ and releases ______ and ______. This is released in the lungs.
Decarboxylated
Acetone
CO2
During an extended fast (starvation), the following would be expected true or false?
After about 1 day, blood glucose levels would remain constant at the low end of the normal range.
True- many mechanisms for maintaining blood glucose levels
During an extended fast (starvation), the following would be expected true or false?
Ketone bodies would rise to high concentrations over the first 20 days.
True- would happen over the first few days
During an extended fast (starvation), the following would be expected true or false?
Blood FA would rise during the first 3 days and very little after that time
True- Lipolysis and oxidation are regulated by energy-lipolysis will not exceed rates of oxidation
During an extended fast (starvation), the following would be expected true or false?
The use of blood ketone bodies by the brain would spare the use of blood glucose.
True- brain can switch to ketone bodies instead of glucose to help maintain blood glucose levels
During an extended fast (starvation), the following would be expected true or false?
The liver would begin to use ketones for energy after 24 hours
False- liver can not use ketones for energy because it lacks the enzymes for converting ketones back into Acetyl CoA
-liver will be using FA instead of Ketones
After 10 days of fasting, which ketone will increase dramatically in the blood ?
Beta-hydroxybutyrate
What 3 things will remain stable after 10 days of fasting?
Glucose
FFA
Acetoacetate (increases but stabalizes at same level of FFA after 10 days)
What timeline in fasting will ketones start to be utilized by the brain for energy?
days 10 to 20
-Beta-hydroxybutyrate will increase dramatically in blood levels from 0 to 10 and then stabalize after day 20
What is the regulatory enzyme for FA synthesis?
AcetylCoA carboxylase
What Apoprotein characterizes VLDL particles?
ApoB 100
The first step in FA synthesis is the formation of _______ from acetyl CoA and Carbon Dioxide
Malonyl CoA
Biotin is a required coFactor for what two enzymes?
Pyruvate carboxylase
Acetyl CoA carboxylase
