Fatty acid digestion and degradation Flashcards
What is a lipid?
compounds of diverse structure that are insoluble in water but souble in organic solvents. mainly composed of hydrocarbon chains.
oils: if liquid at 15-16
Fats: soilid, semi solid
Wxes: solid, higher melting point that fats
Metabolic fuels
Carbs: quick and easiest to produce energy from
Fats: harder to produce energy but provides long, ssustainable energy
Proteins: not a major source of energy bc the body uses them as builing blocks
how does your body use energy from fuels in order
when carb storage is fuel, the body uses mainly carbs
When carb storage is not quite fuel, the body uses both fat and carbs
When your carb storage is empty, the body uses mainly fat.
Compare trans fat vs. cis fat and their physical properties
trans: higher melting point, lower membrnae fluidity -> related to heart disesa
cis: lower metling point, higher membrane fluidity
Majority of the lipids that we use are
fatty acids and glycerollipids
What are TAGs?
Triacylglycerols (TAGs)
What are TAGs stored inside a fat cell as?
stored inside a fat cell (adipocycte) as lipid droplets
After a night’s fast, glycogen stores are low, but lipids are readily avialble. what would happen with an early morning runner?
blood glucose go down
liver glycogen go down
plasma freee fatty acids and blood ketone bodies go up
Can fat be turned into water?
yes
Why is storing fatty acids advantageous?
higher energy yield for the same number of carbons compared to carbohydrates
- glycogen, 65% of wieght comes form water. TAGs are hydrophobic
- Generation of H2O as a result of beta oxidation, ETC and ATP syntheis
Triacylglycerol (TAG) facts
- constitue ~90% of dietary lipids and major form of metabolic energy storage in humans
- most efficient fuel because they are more reduced than carbohydrates
- TAGs are located throughout the body, including under the skin and surround internal organs
- lipid metbaolism ___ require the presencne of oxygen
does
What are fatty acids?
chain of hydrocarbons with -COOH group
What are TAGs
Triglyceride (TAG, fat) is an ester derived from glycerol and 3 fatty acids. TAG are the main consitudent of body fat in humans and other animals, and vefgative fat
How are TAGs metabolized
- TAGs are digested via lipolysis into glycerol and fatty acids
- metabolism of glycerol
- beta oxidation into acetyl coA
can fatty acid be turned into glucose?
a small fraction of TAGs can be turned into glucose (substrate for glucoeogeensis)
Present the pathways for breakdown of triacycle glerol
TAG -> glycorol and fatty acids
In the liver, glycerol can undergo glycolysis and turn into pyruvate
or glycerol can enter gluconeogensis -> glucose
in other tisuses
fatty acids undergo fatty acid oxidation -> turn into acetyl coA -> goes in citric acicd cycle
When is fatty acids linberated, when is it stored
- When energy is reuqired, fatty acids are liberated and oxidized to provide ATP
- When fuel is abundant, fatty acids are syntehsized to and incorportated inoot TAGs and stored as adipose tissue
What is the problem about TAGs not being water soluble
lipids cant be degraded to FAss if they are not soluble in the same medium as degraditive enzymes -> need emulsion, bile salts, lipases, miclees
How are lipids preraed for digestion
- Emulsion in the stomach creates lipid droplets
- bile salts (made from cholesterol in the liver) are instereted into lipid droplets making htem more soluble. bile salts are amphipathic.
- lipases (from the pancrease) attach to the lipid droplet
- free fatty acids and glucerol are carridd in micelles to the plasma membrane of the intestinal epithelial cells
Pancrease functions: exocrine and endocrine
exocrine: digest food like amylases, lipase, protesase
endocrine: secrete hormones
How are diertary TAGs converted to stored TAGs
Lipases are degraded into TAGs and FAs, form a micelle to go into the instestinal cells
fatty acid bidning protein allows them to go through, and fatty acid transport protien transports them to smooth endoplasmic reticumum.
TAGs are resyntheized at the surface of the ER.
TAGs are transported to different tissues to use eenrgy by chylomicrons (a lipoprotein molecule)
What are the different types of TAGs
MAG: monoacyleglerol (1 ester group)
DAG: diacyel glycerol (2 ester groups)
TAG: triacyle glyerol (3 ester groups)
How do hormones control TAG breakdown from adipose tissue
Glucagon/epinephirne actives PKA
and stimulates lipolysis
Activation of PKA leads to phosphorylation and activaation of
- Perillipin (activates a lipase): TAG -> DAG
- hormone senstive lipase (HS lipase): DAG -> MAG
What is the role of albumin?
it delivers fatty acids to the rest of the body
Adipose tissues release FAs into the blod via
albumin
what happens to glycerol? it uses a process that requires eneryg
glycerol formed by lipolysis is absorbed by the liver and phosphorylated, oxididzed into DHAP and isomerized to GAP
GAP is an intermediate in glycoslysi and gluconeogenes. so it can be conerted into pyruvate or glucose
where does beta oxidation take place
mitochonridra
To get into the mitochondria, FAs must be ___ first
activated first, react with coenzyme A to form Acyl coA
What enzyme is needed to activate FAs and how many ATP is needed
2 ATPs
Acyl coA synthase
Acivation of fatty acids can be done by many coacticators. t or f?
t. pathways/enzymes have preferences for one over the other.
Do all fatty acids require the carnitine shuttle to get in the mitochondria?
No, FAs C2-C12 freely diffuses into the mitochornidra.
FAs c14-c20 require carnitine shuttle
How does fatty acisd c14-c20 get into the mitochornira
- free fatty acid is activated into Acyl coA
- diffuses through the outer membrnae via voltage dependent ion channels(not very selective).
- turns from Acyl coA -> acylcarnitine
via carnitine acyl transferase I - acyl carnitine goes through the carnitine-acyl translocase in the inner mitochornidral membrnae
- acyl carnitine is turned to acyl coA via carnitine-acyl transferanse II
What happens if there is a defect in CAT 1? what can u do to treat this? carnitine deficinecy is crucil
build up of fatty acids. eat meat, carbs, supplemnet, consume shorter fatty acid chians
Where does fatty acid oxidation take place?
In animals: mt matrix
In plants: peroxisomes (leaves) and glyoxysomes (seeds)
What are the golas of fatty acid oxidation
oxidize the FA chain 2 C at a time to Acetyl coA
harvest high energy electrons to power oxidative phosphorylation
What are the steps of fatty acid oxiaation?
What does it generate?
Oxidation takes place at the beta carbon
- oxdidation (by FAD)
- hydration
- oxidation (by NAD+)
- Thiolysis by coA
Generates:
FADH2
NADH
Acetyl Coa
What are the steps of fatty acid oxidation (5 steps)
- Activatation of fatyt acid via Acyl CoA synthase
- oxidation via acyl coA dehydrogenase (AD)
- hydration via enoyl coA hydratase (EH)
- oxdiation via 3-hydroxy acyl coA drhydorgensation (HAD)
- cleavage via beta-ketothiolase (KT)
Does acitvation of fatty acid require energy?
Yes, it requires 2 ATP.
How many enzymes does it take to oxidize fatty acids?
repeated series of 4 steps.
but more than 4 enzymes are invvoled.
How does AD differ?
acyl coA dehydrogenase differrs in their specifiicity for hydrocarbon chains of different lengths
What does the complete oxidation of palmitoyl-coA give? how many cycles?
7 cycles
8 acetyl coA
7 NADH
7 FADH2
Whats the number of carbons in oleic acid?
palmitic acid?
(C18:1 delta 9)
(C16:0)
How much energy is genratied from pamityol acid? Make sure to minus 2
1 NADH -> 2.5 ATP
1 FADH2 -> 1.5 ATP
8 Acetyl coA -> 8 ATP, 24 NADH2, 8 FADH2
( 1 acetyl coA -> 1 ATP, 3 NADH, 1 FADH2)
7 NADH
7 FADH2 is made
total energy - 108 - 2 = 106 ATP
What are auxilliary pathways for FA oxidation?
- cis unsaturated fatty acids
requires isomerization to account for double bond - polyunsaturated fatty acids: requires additional isomerization and reduction reactions
- odd chian fatty acids
three enzymatic steps required to deal with propionyl coA on last round of beta oxidation
How to deal with odd chain fatty acids?
in the last step, propionyl coA -> succinyl coA
Requires 1 ATP
How does the succinyl coA compare to acetyl coA in the citric acid cyc;e?
succinyl coA produces 1 GTP, 1 FADH2, 1 NADH
whereas acetyl coA produces 1 GTP, 1 FADH2, and 3 NADH
beyond: can propionyl coA be used to replensih the TCA cycle? can FAs be turned into glucose?
propinyol coA can be used to replensih the TCA cycle.
How to deal with unsaturated FAs?
acyl coA dehydrogenase cannot process cis-enoyl coA
cis-enyol coA is converted into enoyl coA isomerase -> trans enoyl coA.
trans enoyl coA is then used by enoyl coA hydratase
What is the cost of unsaturated fatty acids?
the acyl coA dehydrogenase step is bybassed -> no production of FADH2 during that cycle.
- 1 FADH2
How to deal with polyunsaturated fatty acids?
even numbered double bonds: enoyl coA isomerase and reductases (lose 1 NADH )
odd numbered double bonds: enoyl coA isomerase only (lose 1 FADH2)
Degradation of unstaurated FAs
A). Monounsttuared fatty acids
requires isomeraization to acount for double bond
(lose 1 FADH2, - 1.5 ATP
B) poly unstaruatded
even: reductase and isomerase (each double bond at even loses 1 NADH)
odd: each double bond (-1 FADH2)
Which tissues use ketone bodies to obtain energy?
brain, heart, kidneys, muscles
when does production of ketone bodies arise
when there is an excess of acetyl coA arising from beta oxidation and not enough oxaloacetate available to react with the large amounts of acetyl coA.
What are ketone bodies
substances related to acetone
such as acetoacetate
3- hydroxybutryrate
acetone
why is conversion to ketone bodies necessary
acttyl coA cannot be transported into the blood. need to fuel tissues like the brain and the heart
What is the purpose of ketone bodies
- produced when there is reduced carbohydrate availability
- to provide peripheral tissues (brain, heart and muscles) with alternative fuel soruce. reduces glucose use and muscle protien breakdonw
How are ketone bodies synthesized
- Acetoacetate is formed from 2 acetyl coA molecules
- Acetoacetate is reduced to 3-hydroxybutyrate (NADH -> NAD+)
- Acetone is generated spontaneously by decarboxylation (no enzyme required)
where does ketone body synthesis take place
in the liver
How are ketone bodies broken down (in other tissues)
Ketone bodies are metabolized to generate NADH and 2 Acetyl coAs.
In tisuses using ketone bodies, 3-hydroxybutyrate is oxidized to acetoacetate and is metabolized into 2 molecules of acetyl coA.
Why can’t the liver use ketone bodies?
Because it lacks coA transferase. Therefore acetoacetate and escape the liver and be used by others
How does diabetes and excess ketone body production
- Ketone bodies are moderately strong acids
Overproduction of ketone bodies can occur when diabetes is untreated. -> diaetic ketosis.
If insulin is absent or not functioning, glucose cannot enter liver cells. (you dont have the glut transporter expression where there is high levels of glucose)
energy must be derived from fats -> leading to over production of acetyl coA
how does diabetes contribute to excess ketone body production?
In the liver, acetyl coA build up due to limited OAA (cant be genersated from glucose).
Enhanced fatty acid release from adipose tissue in the abscne of glucose
Excess acetyl coA -> used for the biosynthesis of ketone bodies
How can odd chain fatty acids be used to attenuate ketone body build up?
Propinyl coA -> succinyl coA -> succinate -> fumarate -> malate -> OAA -> citric acid cycle
What fuel source does RBC use?
Glucose
What fuel source does the brain use?
Glucose
Ketone bodies
What fuel source do adipose tissue use?
Glucose
Fatty acids
What fuel source do muscles use?
Glucose
Fatty acids
amino acids
ketone bodies
What is the benefit of using ketone bodies
it curtails protein degradation and prevents tissue failure
Ketone bodies are synthesized from fats , the largest energy store in the body
What is the role of ketone bodies during prolonged starvation
glucose is the predomininant fuel for the brain. however, the brain shifts to ketone bodies during starvation.
short term response: initially protien degradation is the source of carbons for glucog=neogensis. glucose is then released in the blood for the brain to use.
Long-term response: after several days of fasting, the brain beings to use keteon bodies as fuel
The increase in fatty acids ___ the increase in ketone bodies
precedes
What are some changres in metabolism during prolonged starvation?
brain switches from glucose -> ketone bodies
muscle protien degradation slows donw
fuel output of liver: switches from glucose -> keotne bonds
What is ALD?
Adrenoleukodrystrophy
prevents the body from breaking down saturated very long fatty acid chians, leading to build up in the brain, adrenal glands.
Treatment;: oleic aid
whats a treatment for ALD?
unsaturated fatty acids (especially oleic and erucic acids) can compete with saturated VLCFAs for metabolism and reduce their accumulation.
When calculating the ATP yield from ketone bodies, need to consider what?
The oxidation of D-3-hydroxybutyrate makes 1 NADH
