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)