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Biochem Exam 3, Part 3
Lipid and Fatty Acid Metabolism
87
Biochemistry
Professional
10/06/2011

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Term
Describe the structure of a basic fatty acid
Definition
A carboxyl on one end with a chain of carbons.

First carbon from carboxyl is α, second is β, etc. Last is ω.
Term
What distinguishes a saturated fatty acid from an unsaturated fatty acid?
Definition
Unsaturated has a double bond and is therefore less rigid and more liquid at lower temperatures.
Term
How many kilocalories are in 1g fat? How many in 1g carohydrate?
Definition
9kcal/g fat

4kcal/g carbohydrate
Term
Describe Lauric acid
Definition
A 12-carbon saturated fatty acid

Often found in soaps
Term
Describe Palmitic acid
Definition
A 16-carbon saturated fatty acid
Term
Describe Stearic acid
Definition
A 18-carbon saturated fatty acid

Found in beef
Term
Describe Linoleic acid and α-Linoleic acid
Definition
18 carbon fatty acid unsaturated at 3 points

Precursors to prostaglandins, found in coldwater fish
Term
Describe the basic structure if a triacylglycerol (TAG)
Definition
A 3-carbon glycerol backbone with 3 fatty acid chains
Term
Describe the characteristics of a longer fatty acid chain compared to a short chain
Definition
The longer the chain, the more hydrophobic and more unhealthy
Term
What is the main form of fat found in the diet?
Definition
Triacylglycerol
Term
What happens to fats in the small intestine?
Definition
Bile salts emulsify them, forming mixed micelles
Term
After intestinal lipases degrade triacylglycerols, how to do they get into the bloodstream?
Definition
They are taken up into mucosa, reconverted to TAGs, incorporated into chylomicrons, and moved through the lymphatic system to blood
Term
How does a chylomicron in the blood enter a cell as fatty acids?
Definition
A lipoprotein lipase on the capillary wall degrades TAGs, allowing the free fatty acids to enter the cell
Term
Describe the structure of a chylomicron
Definition
Shell of phospholipids with triacylglycerols inside. B48, CIII, and CII apolipoproteins in shell.
Term
What does apolipoprotein CII do?
Definition
It activates lipoprotein lipase on capillary walls
Term
What does apolipoprotein B48 do?
Definition
They are important for clearance of the phospholipid shell after the chylomicron is broken down. The protein is recognized by the liver to recycle the scell.
Term
What happens to the glycerol background during TAG breakdown?
Definition
It can be converted to glycerol-3-phosphate to enter glycolysis (using an ATP and NADH)
Term
Why is it important to turn a free fatty acid into Fatty acyl-CoA as soon as it enters a cell?
Definition
Otherwise, it could be deprotonated at the carboxyl, forming a salt that will act as a detergent, causing damage to membranes
Term
What enzyme converts a fatty acid to fatty acyl-CoA? What does it require?
Definition
Fatty acyl-CoA synthetase, requires ATP and CoA-SH
Term
What is the rate limiting step for β-oxidation?
Definition
Transport into the membrane by the carnitine shuttle
Term
What enzyme converts fatty acyl-CoA to fatty acyl carnitine to get into the matrix?
Definition
Carnitine acyltransferase I

(Carnitine acyltransferase II transforms it back once in the matrix)
Term
Where does β-oxidation occur?
Definition
Inner mitochondrial matrix
Term
Describe the steps of β-oxidation
Definition
1. Dehydrating the fatty acyl-CoA to form a double bond between the α and β carbons

2. Hydrating the double bond to have an OH on the β carbon

3. Dehydrating so the β carbon -OH is now a ketone, forming a di-keto

4. Thiolytic cleavage, releasing Acetyl CoA. The original fatty acyl-CoA is now reduced by 2 carbons
Term
How can β-oxidation be limited?
Definition
If there is no free coenzyme A in the matrix
Term
What is important about the acyl-CoA dehydrogenase in the first step of β-oxidation?
Definition
There are different enzymes for different chain lengths, and these can have genetic deficiencies.

Ex. Some people have "medium" acyl CoA dehydrogenase deficiency
Term
Would β-oxidation take place in a fed or fasted state?
Definition
Fasted
Term
In a fasted state, what happens with the Acetyl-CoA produced in β-oxidation?
Definition
1. 2 Acetyl CoA are converted into acetoacetyl-CoA

2. HMG-CoA synthetase forms HMG-CoA by adding an acetyl CoA

3. Removal of Acetyl CoA produces ketone bodies: acetocetate and D-β-hydroxybutane
Term
What would detection of acetone in the breath indicate?
Definition
Very high ketogenesis due to Atkins diet or uncontrolled type 1 diabetes
Term
What is the purpose of ketones
Definition
A way to take Acetyl CoA from the liver to areas of the body it is needed (even the brain can adapt to this)
Term
How can ketone bodies acetocetate and D-β-hydroxybutane be converted back into 2 Acetyl CoA
Definition
It's fairly simple, they are converted back to Acetoacetyl-CoA by β-ketoacyl-CoA transferase

Thiolase splits it into 2 Acetyl CoA
Term
What enzyme interchanges ketone bodies acetocetate and D-β-hydroxybutane?
Definition
D-β-hydroxybutyrate dehydrogenase
Term
Where does ketone synthesis occur?
Definition
Mitochondrial matrix of the liver
Term
How does an energy-rich state promote fatty acid synthesis?
Definition
Insulin promotes acetyl-coA carboxylase to turn acetyl-CoA into Malonyl CoA, used to make fatty acids
Term
How does the presence of malonyl CoA inhibit β-oxidation?
Definition
Malonyl CoA inhibits carnitine acyl-transferase in the carnitine shuttle
Term
How would low blood glucose inhibit fatty acid synthesis
Definition
It would deactivate acylCoA carboxylase, leaving Acetyl CoA to be converted to glycose
Term
Describe the structure of malonyl CoA
Definition
Acetyl CoA attached to a carboxylic acid derived from bicarbonate

Its C-C bond is important for anabolism
Term
What are three parts in the acetyl CoA carboxylase?
Definition
1. Biotin carboxylase
2. Biotin carrier protein
3. Transcarboxylase
Term
How does acetyl-CoA carboxylase convert acetyl-CoA into malonyl CoA?
Definition
A biotin side chain attaches to Acetyl CoA then uses ATP and biocarbonate to add on carbon, forming malonyl CoA
Term
Where is malonyl CoA formed?
Definition
Cytosol
Term
What are the steps of fatty acid synthesis?
Definition
1. Malonyl CoA is activated with primer acetyl group

2. Reduction of keto group to an alcohol

3. Elimination of water to form a double bond

4. Reduction of double bond to form a saturated acyl group (resulting in a final addition of 2 hydrocarbons)
Term
Even though fatty acid synthesis (condensation, reduction, elimination, reduction) is basically reversing β-oxidation (reduction, hydration, reduction, cleavage) why are they NOT considered reversible processes?
Definition
A different set of enzymes is used
Term
What is the final product of fatty acid synthesis?
Definition
Palmitate
Term
What energy sources are needed for fatty acid synthesis
Definition
7 ATP, but more significantly 14 NADPH

7ATP is >1 glucose, 14 NADPH is about 7 glucose
Term
Give 2 sources of NADPH
Definition
1. PPP
2. Malate -> pyruvate via malic enzyme
Term
What three carbon sources can transverse the matrix membranes?
Definition
Citrate, malate, pyruvate
Term
How does insulin promote formation of Malonyl-CoA?
Definition
By activating citrate lyase (forming acetyl CoA) and acetyl CoA carboxylase (forming Malate)
Term
How does glucagon promote Malonyl CoA formation?
Definition
Trick question! Why would glucagon promote malonyl CoA and fatty acid synthesis?
Term
How does glucagon/epinephrine inhibit malonyl CoA formation?
Definition
By inhibiting acetyl-CoA carboxylase
Term
What are positive regulators of acetyl-CoA carboxylase?
Definition
Insulin, citrate
Term
What are negative regulators of acetyl-CoA carboxylase?
Definition
Glucagon, epinephrine, palmitoyl CoA
Term
Define ecosanoid
Definition
A signaling molecule derived from oxidation of essential fatty acids
Term
What are essential fatty acids?
Definition
ω-6 or ω-3 fatty acids that only plants have the enzymes to make (can also be found in some things, like fish, that eat them)
Term
Why do we need ω-3 fatty acids?
Definition
They are needed for regulatory lipids that mediate inflammation (prostaglandins, leukotrines)
Term
In polyunsaturated fatty acids, where is the double bond found?
Definition
Between carbon 9 and the ω carbon
Term
What enzyme do plants have for making ω fatty acids that mammals lack?
Definition
Desaturase
Term
What is the name of the pathway by which phospholipid containing arachidonate is turned into prostaglandins?
Definition
The cyclooxygenase pathway
Term
What enzyme converts arachidonate 20:4 to cyclooxgenized prastaglandin precursor PGH2?
Definition
COX
Term
What drugs inhibit COX?
Definition
Aspirin, ibuprofin
Term
How does aspirin inhibit COX?
Definition
By acetylating an essential serine residue in the active site (covalent modification)
Term
How do ibuprofen and naproxen inhibit COX?
Definition
By acting as competitive inhibitors
Term
What enzyme converts arachidonate into leukotriene precursors?
Definition
Lipoxygenase
Term
What drug can affect leukotriene action, and how does it function?
Definition
Singulair, by binding antagonistically to leukotriene surface receptors on cells
Term
What are the building blocks of cholesterol?
Definition
Isoprene, derived from Acetyl CoA
Term
Why is cholesterol necessary for life?
Definition
It is important in membranes, bile, steroid hormones
Term
What is the rate limiting step of cholesterol synthesis?
Definition
The conversion of acetate to mevalonate
Term
List the carbon intermediate steps of cholesterol synthesis
Definition
1. Acetate
2. Mevalonate
3. Activated (phosphorylated) isoprene
4. Squalene
5. Cholesterol
Term
What enzyme is the target for stain drugs and the rate limiting step for cholesterol synthesis?
Definition
HMG CoA reductase
Term
Why is cholesterol synthesized more in the fed state?
Definition
Because it is derived from a carbohydrate, acetyl CoA
Term
Why are statin drugs not dangerous? (the body does need some cholesterol to function)
Definition
Statins only work in the liver, other tissues can make enough for cholesterol needs

Therefore okay for "de novo" synthesis
Term
What are the energetic costs to form cholesterol?
Definition
Several ATP, but more significantly many expensive NADPH
Term
How many acetate molecules would be needed for one cholesterol molecule?

(Not sure if she would ask this)
Definition
12
Term
What is the regulatory protein on VLDL?
Definition
ApoB-100, which binds to LDL receptor
Term
How are LDL particules formed?
Definition
1. Liver sends out VLDL to carry fat to the body, VLDL picks up proteins along the way to facilitate its metabolism

2. LDL are derived from VLDL that have transported all of their triacylglycerol to peripheral tissues
Term
What is the function of HDL particles?
Definition
To pick up cholesterol in peripheral tissues and return it to the liver ("reverse cholesterol transport")
Term
How are HDL particles formed?
Definition
They are not synthesized, but form once they pick up apoA1 from chylomicrons
Term
List the four lipoproteins in order from most triaglycerols to least
Definition
Chylomicrons, VLDL, lDL, HDL
Term
Which lipoproteins have high levels of cholesterol?
Definition
LDL and HDL
Term
What cholesterol is "bad" and what is "good"?
Definition
LDL- bad
HDL- good
Term
Where is ApoB-48 found?
Definition
Chylomicrons
Term
Where is ApoB-100 found and what does it do?
Definition
VLDL and LDL, binds to LDL receptor on cell membranes
Term
Where is ApoC-II found and what does it do?
Definition
It is in chylomicrons, VLDL, and HDL and it activates lipoprotein lipase
Term
Where is ApoC-III found and what does it do?
Definition
It is in chylomicrons, VLDL, and HDL and it inhibits lipoprotein lipase
Term
How are lipoproteins cleared from the bloodstream?
Definition
By receptor mediated endocytosis
Term
Is HMG-CoA reductase inhibited or activated by insulin?
Definition
Activated
Term
How does cholesterol regulate HMG-CoA reductase?
Definition
Cholesterol stimulates proteolysis of HMG-CoA reductase (negative feedback)
Term
How much can diet and exercise change serum cholesterol levels?
Definition
10-20%
Term
In insulin resistance, what process is oddly promoted?
Definition
Gluconeogenesis (increasing blood glucose and increasing cholesterol)
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