Lecture 12 Flashcards
When someone loses weight, where does the fat go?
CO2
How are fatty acids transported into the mitochondria, generally?
They are broken down first, moved in through transporters, then rebuilt
How many carbons does each round of beta-oxidation remove?
Two
How many rounds of beta-oxidation would a 16-carbon fatty acid go through?
7, because in the seventh cut, you split a four-C molecule into two 2-C molecules. No need for an 8th round
Which product is the committed step in fatty acid synthesis and why?
Malonyl-CoA, because it is not used in beta-oxidation, only lipid biosynthesis. This helps prevent futile cycling.
What are the general steps of fatty acid breakdown?
Dehydrogenation, hydration, dehydrogenation, and thiolytic cleavage
What is the first detailed step of fatty acid breakdown (assume fatty acyl-CoA was made)?
acyl-CoA DH cleaves the bond between the alpha and beta carbons. A C=C bond is formed. FADH2 is made that donates e- to Q like Complex II
What is the second detailed step of fatty acid breakdown?
Water is added and a hydroxyl hydrates beta carbon, thus getting rid of the C=C bond.
What is the third detailed step of fatty acid breakdown?
DH oxidizes the beta carbon, yielding a carbonyl. NADH is produced that goes to NADH DH, then its e- enter the respiratory chain
What is the fourth and final detailed step of fatty acid breakdown?
Thiolase adds CoA-SH to the fatty acid, which means the fatty acid gets cleaved 2-C halves, each with an acyl-CoA. 1 Acetyl-CoA is generated, which can then enter ketogenesis or the TCA cycle
Where else do we see the DH, hydration, DH pattern?
TCA cycle with succinate and the oxidation of Leu
Explain the beta-oxidation of a fatty acid with 1 cis-double bond
After beta-oxidation, an isomerase converts the cis-double bond to a trans-double bond, which then continues beta-oxidation and produces acetyl-CoA
Explain the beta-oxidation of a fatty acid with 2 cis-double bonds
Several rounds of preliminary beta-oxidation. Then one cis-double bond converts into a trans double bond, which then gets moved over. A reductase gets rid of the other cis-double bond and the trans-double bond gets moved over to the alpha and beta carbons so that acetyl-CoA can be formed. NADP+ is generated in the reductase step.
Explain beta-oxidation of a fatty acid with an odd-numbered chain length
Use propionyl-CoA carboxylase (which uses biotin, HCO3-, and ATP). Uses Co-B12 to make succinyl-CoA
Are all ketone bodies ketones?
No
Which are the 3 primary ketone bodies we make?
Acetone
D-beta-hydroxybutryate
Acetoacetate
Why does the brain use ketone bodies as a fuel source when fasting?
Free fatty acids cannot pass through the blood brain barrier, but ketone bodies are able to
What is the first step of ketogenesis?
A thiolase takes 2 acetyl-CoA and combines them to make acetoacetyl-CoA. A CoA-SH is released.
What is the second step of ketogenesis?
HMG-CoA synthase adds 1 acetyl-CoA to acetoacetyl-CoA to generate HMG-CoA. One CoA-SH is released.
What is the third step of ketogenesis?
HMG-CoA lyase converts HMG-CoA into acetoacetate
What are the paths that acetoacetate can take?
It can decarboxylate to acetone, it can dehydrogenase to D-beta-hydroxybutryate, or it can enter the blood. Basically, it can convert to other types of ketone bodies.
What happens when OAA levels are low?
Gluconeogenesis cannot occur, meaning the TCA cycle cannot occur either, so acetyl-CoA is used to make ketone bodies in the mitochondria
How many acetyl-CoA molecules per ketone are generated outside the liver?
2 acetyl-CoA/ketone
What happens when there are high blood concentrations of ketones?
Ketoacidosis. The blood acidifies and the TCA cycle is unable to regenerate intermediates
Pros and cons of the keto diet?
Pros: lose weight
Cons: ketoacidosis, little vitamin intake, and little variety in diet (steak and eggs every day)
From what molecules is malonyl-CoA made?
acetyl-CoA
What is the first step of fatty acid biosynthesis (do not assume malonyl-CoA was made yet)?
Move acetyl-CoA from the matrix into the cytosol. Do this by first combining acetyl-CoA with OAA to make citrate, which goes through a transporter to cytosol. The citrate then reacts with ATP and CoA-SH to regenerate acetyl-CoA and ADP + Pi.
What is the second step in FA biosynthesis (hint – acetyl-CoA just got moved to the cytosol)?
Make malonyl-CoA using acetyl-CoA carboxylase (similar to pyruvate carboxylase)
How does acetyl-CoA carboxylase work?
The biotinyl arm takes a CO2 from HCO3- and moves it over to acetyl-CoA, which combine to form malonyl-CoA
What is an allosteric activator of acetyl-CoA carboxylase? Allosteric inhibitor?
Activator: citrate
Inhibitor: palmitoyl-CoA (product downstream, comes after malonyl-CoA). Glucagon and epinephrine trigger phosphorylation AKA inactivation because you don’t want to make FA when you’re hungry
Why does eating lots of fructose (i.e., high fructose corn syrup) lead to fat storage?
Citrate inhibits PFK-1, but fructose bypasses this step so it keeps forming citrate. This signals to the body that it’s full and should store fat.
