Oxidation of Fatty Acids & Ketone Bodies
What do long fatty acid chains need to get to the plasma membrane?
What happens as soon as the fatty acid gets through the plasma membrane? Fatty
Fatty acid-binding protein along with ATP and CoA activates it so Fatty Acyl CoA. Fatty Acyl CoA Freely goes through the outer mitochondrial membrane
What is carnitine's effect on transport of fatty acid chains?
exchanges CoA for Carnitine allowing the fatty acid chain to cross the inner mitochondrial membrane where charnitine does another exchange. Carnitine is now replaced with CoA inside of the inner membrane of mitochondria.
Carnitine acyl trasferase
transfers activated fatty acyl group from CoA to -OH and makes acylcarnetine ester, another trasferase transfers FA back to CoA
Translocases in the inner membrane of mitochondria
help the FA in the inner membrane crossing
What takes place after the Fatty Acid chain, is activated to Fatty acyl CoA, in the inner membrane of mitochondria? Fatty
Fatty acyl CoA does through B-oxidation making FADH2 and NADH then the resulting Acyl CoA goes either to the liver to make ketone bodies or to the TCA cycle (making more NADH,FADH2 and GTP there)
What FA are used as fuel between meals, fasting and increased fuel demand?
Mainly long-chains from adipose tissue TAG stores
What are the major long-chain that are oxidized?
Palmitate, Stearate, Monounsaturated oleate and polyunsaturated essential linoate
Which of the long-chain fatty acids is made from glucose?
How many carbons does palmitate have?
How many carbons does strearate have?
How many carbons does oleate have?
How many carbons does linoate have?
What kind of FA does animal fat usually contain?
Saturated and monounsaturated
What kind of FA chains are found in dairy fat?
When insulin is decreased and glucagon activates lipolysis what binds to the free FA to be transported to the tissue?
What percentage is the dietary fat taken in as TAG?
95% which is broken down and reassembled in chylomicrons
release long-chain FA from adipose TAG during fasting, the free FA are transported with albumin and they can enter the cell by saturable transport and by diffusion
Where is long-chain acyl CoA synthetase present?
long-chain acyl CoA synthetase presents itself in the ER, outer mitochondria and perixosomal membranes
What does acyl CoA synthetase do?
It takes the fatty acid and an ATP and a CoA and makes an Fatty acyl CoA an AMP and 2Pi. In sum:
FA+ATP+CoA --- > Fatty Acyl Coa+AMP+2Pi
What is Acyl CoA is made into in the ER?
TAG and phospholipids
What is Acyl CoA is made into in the peroxisomes?
Oxidation and plasmalogen
What is Acyl CoA is made into in the mitochondria?
Energy via B-oxidation
CPT (Carnitine palmytol trasferase I) is inhibited by _______.
B-oxidation of long-chain FA
cleaves fatty acyl group into 2C acetyl CoA unit and begins at the carboxyl end, the Beta Carbon is oxidized into keto and makes NADH and FADH2 (hence the name)
The 4 reaction per B-oxidation cycle and the enzymes involved:
Dehydrogenase makes a double bond
Enoyl CoA hydrolyses makes a -OH group
B-hydroxy acyl CoA dehydrogenase- OH is made into a =O (keto)
B-keto thiolase along with CoASH- activates and then alpha-beta bond is cleaved
The result is 2C less.
How is the energy from FADH2 gets transferred to the Electron transport chain?
ETF (electron transport flavaprotein) in the mitochondria's matrix accepts the electrons then transfers them to the ETF CoQ oxidoreductase which then transfers them to CoQ in ETC. In sum :
FADH@--- > ETF--- > ETF-QO --- > CoQ (in ETC)
What are half of the FA in the human diet as far as saturation? What are two most common FA?
Half is unsaturated with cis double bands. Most common are oleare and linoleate.
Cis double bonds and B-oxidation
to undergo B-oxidation must be isomerized to trans or reduced
What happens if the FA has an odd number of carbons?
Thiolase cleavage results in Acetyl CoA and Propionyl CoA. Propionyl CoA --- > succinyl CoA which then goes into gluconeogenesis for the making of glucose
What is the fate of medium dietary FA chains and why?
They are not stored in adipose TAG because they are more water soluble. They enter liver, and are oxidized to acetyl CoA via b-oxidation
What are important things to know about B- oxidation ?
is strictly aerobic, and it regulated by the cells energy needs. Inhibited by AMP,NADH, FADH2 and activated by insulin
Acetyl CoA carboxylase
takes Acetyl CoA and makes Malonyl CoA
What kind of FA chains end up in peroxisomal oxidation?
Very-long-chain FA (24-26)
What happens in the peroxisomal oxidation?
Similar to B-oxidation generates NADH via B-oxidation.
Similar to B-oxidation generates NADH via B-oxidation.
An oxidase, it makes peroxide which is neutralized by catalase.
What are the most common branched-chains of FA in the diet?
Phytanic acids and pristanic acid ( they are the degradation product of chlorophyll in green vegetables
How are branched chained oxidized?
In peroxisomes, to branched C8 FA then transferred to mitochondria. The result is Propionyl CoA (needed for gluconeogenesis) and acetyl CoA via alternative turns of cutting.
Where does microsomal w-oxidation occure?
How does w-oxidation occure
W-methyl group is oxidized to an -OH by cytochrome P450, molecular oxygen and NADPH, then dehydrogenase converts it to a carboxylic acid (coo-) and finish with B-oxidation.
What is the fate of the w-FA?
First forms 6-10 carbon dicarboxylic acids, after entering blood it either oxidizes are medium chains FA or excreted.
Where are ketone bodies made?
In the matrix of mitochondria from Acetyl CoA product of B-oxidation and is possible because THIOLASE REACTION IS REVERSABLE
reacts with Acetyl CoA with the enzyme HMG-synthase to make HMG-CoA
is a ketone body (50% of the) product when HMG looses the Acetyl CoA. Acetoacetate spontaneously converts to Acetone
the other 50% of the ketone bodies made, can be made into acetoacetate by a dehydrogenase
Oxidation of ketone bodies
thiotransferase ( is in low levels in the liver, clearly because we want to make KB in the liver not break them) activates acetoacetate to acetoacetate CoA . then the same thiolase as in B-oxidation cleaves it into 2acetyl CoA
What are the amino acids that can generate ketone bodies?
Leucine, isoleucine, tryptophan, phenylalanine and tyrosine
When would acetoacetyl be activated to acetoacetyl CoA in the Cytosol?
During cholesterol synthesis
When is cytosolic acetyl CoA needed?
ACH in neurons
What cells can use ketone bodies?
All including (crossing placenta) except RBC and liver