biochem exam 2 - fatty acid catabolism 7 Flashcards
Lipids
Lipids include many types of molecules
- They are not defined by their structure; they are defined by having low solubility in water and high solubility in non-polar solvents
- They are largely hydrophobic
- OR they can be amphipathic (remember?)
Functions:
* Energy Storage
* Fats and oils
* Structural
* (A)glycerophospholipids(B) sphingolipids(C)sterols(membranes)
* Other/Specific Biological Activities
* enzyme co-factors, electron carriers, light-absorbing pigments, hormones, etc.
Storage Lipids: Fatty Acids
The simplest lipids are fatty acids which are also constituents of many more
complex lipids
- Their basic structure exemplifies the amphipathic lipid model
- A long hydrocarbon chain (“tail” – hydrophobic)
- A terminal carboxyl group (“head” – hydrophilic)
- Fatty acids are carboxylic acids with highly reduced hydrocarbon chains (4-36 carbons; C4 – C36)
- Most natural fatty acids are unbranched
- Some have double bonds (stay tuned)
- Almost all natural fatty acids have an even number of carbons (12-24)
- Membrane lipids are 16-20 carbons long
Saturated and Unsaturated Fatty Acids
Saturated
- * NO DOUBLE BONDS
- Monounsaturated
- ONE DOUBLE BOND
- Polyunsaturated
MORE THAN ONE
DOUBLE BOND - C1 = carboxylic acid
Most double bonds are at C9, C12, C15
Saturated and Unsaturated Fatty Acids
Saturated chain adopts extended conformations
- Unsaturated fatty acids are slightly more abundant in nature
- The double bonds in natural unsaturated fatty acids are commonly in cis configuration
- Kinks the chain
- Prevents close packing
and increases flexibility - What is the impact of this?
Saturated and Unsaturated Fatty Acids: Naming
The first number is how many carbons are present
- The number after the colon is the number of double bonds present
- The number(s) after the delta denote which carbons have the double bonds
- The ω (omega) numbers refer to how many carbons away from the methyl end of the fatty acid chain that the first carbon=carbon double bond appears
how do we break down fatty acids?
fatty acid catabolism!
Energy Storage Lipids: TriAcylGlycerols (TAGs)
Fatty acids are often incorporated in Triacylglycerols (also called triglycerides, fats, TAGs)
- These are fatty acid esters of glycerol
- Three fatty acids each in ester linkage to 1 glycerol
3 -acyl-glycerols
reduced carbon chains and have a lot energy
lipases
- enzymes that hydrolyze TAGs to yield F.A’s
Energy Storage Lipids: TriAcylGlycerols (TAGs)
triacylglycerols as storage fuels: advantages
- high energy density (J/g) has about 2x more energy than carbohydrates
- not water-soluble (compared to carbohydrates)
- do not increase osmotic pressure
- do not bind water (no extra mass)
- chemically inert because they cannot bond to water
the energy is in the fatty acids!
use as fuels: problems
- need to be emulsified to be transported
- need special protein carriers
- “InertAn Aside: TAGs→Fatty Acids: What about the Glycerol?” bonds are hard to break
“Emulsify”
- to force two or more liquids (fat and water) that are normally undissolvable into a mixture. An “emulsifier” stabilizes the emulsion – usually amphipathic.
The primary transporters of lipids from the small intestine to other parts of the body are…
A
Acyl transferases
B
Fatty acid transferases
C
Chylomicrons
D
Serum albumins
C
Chylomicrons
D
Serum albumins - go from adipose tissues to the cells
Fatty acids are attached to ___ for transport from the cytosol into the mitochondria
A
Coenzyme A
B
Creatine
C
Carnitine
D
Serum albumin
C. Carnitine
Which of the following is true of β-oxidation of fatty acids?
A
In a single round, one molecule of FADH2 and one molecule of NADPHare produced.
B
It is the same for both saturated and unsaturated fatty acids.
C
Fatty acids are broken down into two-carbon units
D
It occurs in the intermembrane space of the mitochondria
not D because it is in the matrix
not A because in a single round, we get way more FADH2
An Aside: TAGs→Fatty Acids: What about the Glycerol?
glycerol + ATP to glycerol-3 phosphate to dihydroxyacetone phosphate that can either go to glycolysis or gluconeogenesis
In Step 5 of glycolysis, Dihydroxyacetone phosphate (DHAP) from Step 4 is converted to Glyceraldehyde-3- phosphate (G-3-P)☺ through triose phosphate isomerase
About 95% of the biologically available energy of TAGs resides in the FAs (the focus of this chapter). 5% comes from the glycerol via glycolysis
Outline of Fatty Acid Catabolism
- digestion and transport of dietary fats
- mobilization and transport of stored fats
- fatty acid activation
- fatty acid transport into the mitochondria
- beta-oxidation of fatty acids to acetyl-CoA
- simple case: fully saturated FA with an even number of carbons
- special case: unsaturated FA (double bonds), odd number of carbons
- other stuff: ketone bodies - remember, acetyl-CoA is oxidized to CO2 in the CAC
- electrons released from the oxidation in the CAC go to the ETC to ATP
How do we get our TAGs?: Diet/Digestion
Fats ingested in diet and go to the gallbladder
- if you do not have a gallbladder, you have to eat low fat diet
- bile salts emulsify dietary fats in the small intestine, forming mixed micelles
- intestinal lipases degrade triacylglycerols
- fatty acids and other breakdown products are taken up by the intestinal mucosa and converted into triacylglycerols
- triacylglycerols are incorporated with cholesterol and apolipoproteins into chylomicrons
- lipoprotein lipase activated by apo-C-II in the capillary converts triacylglycerols to fatty acids and glycerols
- fatty acids are oxidized as fuel reesterified
simplified
- eat fat
- fat goes to the gallbladder
- fats go into chylomicron
- chylomicron releases fat into the blood
- blood takes fat to cells
- cell either stores it or uses it for energy
summary of dietary lipids
intestine - emulsification (bile)
hydrolysis (TAG to FA) using lipase
intestinal walls - FA’s to TAGs
incorp. in chylomicrons
transport
- lymph system and blood system
muscle and adipose tissue
- TAG to FA (lipoprotein lipase [LPL])
- FA enters cells
- oxidation or storage (TAG)
How do we get our TAGs?: From Storage – Adipose Tissue
low energy, emergency
activate hormones glucagon or epinephrine
TAG hydrolysis (to FA) and transport (carrier serum albumin)
FA catabolism for energy
- glucagon or epinephrine binds the receptor
- ATP to cAMP
- PKA activates hormone-sensitive lipase by adding pi
- PKA add pi to CGI
- CGI activates ATGL to turn TAG to DAG to MAG
- MGL
- MAG sent out of the cell to the blood
- MAG binds serum albumin
- beta oxidiation, CAC, repsirtoy chain break down into energy
Notes:
* 4: Phos. of perilipin causes
* 5: CGI to recruit ATGL (lipase)
* 6:ATGL:TAG→DAG
* 7: Phos. of HSL (hormone-sensitive lipase): DAG → MAG
* 8: MGL (lipase): MAG→ FAs
Now that we’ve entered the cell…Fatty Acid Activation?
Catabolism happens in the mitochondrial matrix, but the FA cannot pass through the membranes without first being activated. This step is known as Fatty Acid Activation.
In short, the fatty acid (energy inert) is adenylated (ATP→AMP + PPi + E)
PPi is formed (2 ATP equivalents! which is hydrolyzed → energy)
That released energy allows for the formation of the high energy fatty acyl-CoA (thioester!)
ATP + FA
then CoA-SH attacks the fatty acud adenylate to form fatty acid-CoA
Now let’s move the activated FA into the mitochondria!
Activated fatty Acyl-CoA cannot pass through the mitochondrial membranes, so we have to go through the carnitine shuttle
Even though we just activated our FA, because of that CoA bit, it can’t pass through.
- So we do two reactions that switch the CoA for carnitine, and then we switch back.
Notes:
Outer membrane: Fatty Acyl-CoA + Carnitine → FA-Carnitine + CoA (Transport to Matrix)
Inner Membrane, inside: FA-Carnitine + CoA → Fatty Acyl-CoA + Carnitine (recycles carnitine)
Fatty Acyl-CoA is in the Matrix Now!
Time to oxidize!
Oxidation of the FA component of the fatty acyl-CoA is accomplished by an enzyme in the mitochondrial matrix
beta-oxidation of even saturated FA involves a repeated sequence of 4 rxn:
- oxidation by a dehydrogenase
- hydration by a hydratase
- oxidation by a dehydrogenase
- thiolysis by thiolase
oxidation of unsaturated fatty acids requires additional steps
oxidation of add chain (3,5,7 ect) fatty acids requires additional steps
beta oxidation of FA’s
Notes:
* 1: Oxidation of an alkane to an alkene by dehydrogenation (CAC #6)
- 2.Rehydration. The addition of water is always trans (- OH and H added across the double bond). (CAC #7)
- Oxidation again (this time –OH to carbonyl) (CAC #8)
- Cut off acetyl-CoA (2-C molecule) and add CoA (energy) to the remaining hydrocarbon. This reaction energetically drives the previous 3. - thiolysis
- Addendum: the fatty acid is 2 carbons shorter after each round of oxidation.
repeated cycles of beta-oxidation of FA’s
for a C-16
7 cycles = 14
1 acetyl coa left
1 acetyl coa (2-C) per cycle
+ 1 NADH + 1 FADH2 per cycle
(carbon #/2) - 1 = # of cycles
- 1 acetyl CoA per cycle + 1 left over is the # of acetyl CoA’s
so basically the# of acetyl-CoA’s = # of carbons/2
ENERGY yield from oxidation
n = carbons
n/2 = # of acetyl-CoA
n/2 - 1 = # of FADH2 & NADH
each acetyl-CoA entering the CAC makes:
- 3 NADH, 1 FADH2, 10 ATP’s
so if the # of acetyl-CoA = 7, 7 x 10 = 70 ATP’s from that acetyl CoA
palmitoyl coa - 16 carbons
- 16/2 = 8 acetyl CoA’s
- (16/2) - 1 = 7 NADH & FADH2
- 8 x 10 = 80 ATP’s from acetyl CoA
- 1.5 x 7 = 10.5 ATP’s from NADH
- 2.5 x 7 = 17.5 ATP’s from FADH2
- 10.5 + 17.5 = 28 ATP’s from NADH & FADH2
yield 80 + 28 = 108 ATPs
BUT!
* Fatty acid activation required 2 ATP so
the net yield is: * 108 - 2 = 106 ATPs
Special Case: Unsat. FAs (Double Bond!)
- Notes:
oxidation = lose e- or really lose H’s :) - Remember the steps of oxidation at saturated FA:
- Remove 2H
- Add H2O
- Remove 2H
- Remove Acetyl-CoA
- Well, at the double bond, Step 1 has already been done (because Step 1 creates a double bond in a Sat. FA)
- So, at the double bond, turn it from cis to trans with isomerase, skip step 1, and continue.
Special Case: Polyunsat. FAs (Multiple Double Bonds!)
- Notes:
- With one double bond we just have the isomerase.
- With multiple, we have to add 2,4-dienoyl-CoA reductase
- In combination with isomerase, the cis double bond is removed, and the trans double bond is shifted (position is wrong for the enzyme)
- Multiple double bonds make this FA less energy-rich.
