Lipid Catabolism Flashcards
___ is a protein that coats the lipid droplet in adipocytes.
Perilipin
Describe the process by which lipids are mobilized from adipocytes in the fasted state.
Glucagon / Epinephrine binds to the GPCR, activates Gas, stimulates adenylyl cyclase, produces cAMP, activates PKA, phosphorylates hormone sensitive lipase and perilipin, phosphorylation of HSL activates it and phosphorylation of perilpin allows access to for HSL to inside of adipocyte. HSL cleaves TAGs into glycerol and FFAs. Glycerol diffuses into blood directly, FFAs bind to albumin and are transported in blood. Both end up in liver where glycerol enters gluconeogenesis and FFAs undergo beta oxidation.
In the fasted state, the body releases _____ FFAs relative to energy needs.
More
Over production of FFAs for Beta Oxidation during fasting results in the use of ________ to rebuild the TAGs.
Explain why this happens and why this is beneficial.
A lot of energy
Adipose has no meter for energy demand, so it does not know how much energy is needed and when it has supplied enough. Thus, it releases more than enough FFAs available for energy production and the remainder ~65% is taken back up by the liver and transferred back to adipose tissue. Although it costs energy, this is beneficial because it ensures adequate energy supply and maintains blood homeostasis with respect to serum lipid.
Addition of each FA to produce TAGs again requires __ ATP.
6
Why is it important to transport FAs into the mitochondria for degradation?
1) Physical separation of FA degeneration and FA synthesis is important to avoid futile cycle
2) FA breakdown is located at site of TCA so acetyl coA produced from B-Ox can enter TCA directly.
Describe the process of FA transport into the mitochondria.
In the cytosol, the FFA undergoes reaction such that FFA is transferred to carnitine and coA-SH is released in cytosol. Carnitine-FFA is transported to intermembrane space via Carnitine Acyltransferase 1 (CAT1) and then from IMS to matrix via CAT2 that attaches to the carnitine-FFA and moves it through a transporter in the inner mitochondrial membrane. Once in the matrix, the Carnitine-FFA undergoes another reaction that results in the release of carnitine and the conjugation of the FFA with coA once more. The free carnitine attaches to CAT2 and moves back out to the cytosol and the FFA remains in the matrix to undergo beta oxidation.
Beta Oxidation
- Describe this process in general.
- What FA structure do FFAs converge on for degradation purposes?
- What is the first enzyme in the process of beta oxidation? What is its substrate/product/co-products?
- What must be done to unsaturated fatty acids before they can undergo beta oxidation?
- In general, the FFA gets cleaved into acetyl coA by oxidizing the carbon that is in the beta position wrt carbonyl carbon.
- Palmitoyl coA
- Acyl-coA Dehydrogenase (substrate = palmitoyl coA, product = trans-enoyl coA, co-product = FADH2)
- Must isomerize cis double bonds to trans double bonds
Beta Oxidation Odd Chain FAs
- What unique product is made when odd chain fatty acids are oxidized?
- Where do odd chain fatty acids come from?
- What 2 vitamins are necessary for odd chain FA oxidation?
- Propionyl coA
- Fermentation by gut bacteria and amino acid catabolism
- Biotin and B12
When a person has biotin deficiency, which enzyme in odd chain FFA oxidation will be impacted?
Propionyl coA carboxylase
- When a person has vitamin B12 deficiency, which enzyme of odd chain FFA oxidation will be impacted
- What product in the odd chain FFA pathway will accumulate?
- Methyl-malonylcoA mutase
- L-Methylmalonyl coA
Explain why ketone bodies are produced in a state of fasting/starvation.
Gluconeogenesis that is ongoing removes OAA from the TCA. As such, TCA flux slows due to low amounts of intermediates. At the same time, beta oxidation is occurring and producing acetyl coA. The acetycl coA cannot enter TCA due to lack of intermediates, so instead it is converted to ketone bodies which can be used by many tissues, including the brain, for energy production.
Where are ketone bodies produced? Where do they go after being made?
The liver produces ketone bodies from acetyl coA
The brain can use ketone bodies when glucose levels are low, however blood glucose (if available) will largely be conserved for the brain so peripheral cells will instead utilize ketone bodies in order to preserve glucose for the brain.
Is the liver able to break down ketone bodies?
No - it lacks a key enzyme in the conversion of acetyl coA to acetoacetate so it cannot breakdown acetyl coA to ketone bodies
In alcoholic ketoacidosis in the fasted state, which ketone body will predominate?
Does this ketone body appear on urine dipstick?
Beta Hydroxybutarate –> ethanol metabolism produces a lot of NADH, so as a result beta hydroxybutarate will be produced in an effort to regenerate NAD+
No
