Oxidation of Fatty Acids & Ketone Bodies

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1

What do long fatty acid chains need to get to the plasma membrane?

Albumin

2

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

3

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.

4

Carnitine acyl trasferase

transfers activated fatty acyl group from CoA to -OH and makes acylcarnetine ester, another trasferase transfers FA back to CoA

5

Translocases in the inner membrane of mitochondria

help the FA in the inner membrane crossing

6

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)

7

What FA are used as fuel between meals, fasting and increased fuel demand?

Mainly long-chains from adipose tissue TAG stores

8

What are the major long-chain that are oxidized?

Palmitate, Stearate, Monounsaturated oleate and polyunsaturated essential linoate

9

Which of the long-chain fatty acids is made from glucose?

Palmitate

10

How many carbons does palmitate have?

16 C

11

How many carbons does strearate have?

18 C

12

How many carbons does oleate have?

18 C

13

How many carbons does linoate have?

18 C

14

What kind of FA does animal fat usually contain?

Saturated and monounsaturated

15

What kind of FA chains are found in dairy fat?

Medium chains

16

When insulin is decreased and glucagon activates lipolysis what binds to the free FA to be transported to the tissue?

Albumin

17

What percentage is the dietary fat taken in as TAG?

95% which is broken down and reassembled in chylomicrons

18

Lipases

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

19

Where is long-chain acyl CoA synthetase present?

long-chain acyl CoA synthetase presents itself in the ER, outer mitochondria and perixosomal membranes

20

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

21

What is Acyl CoA is made into in the ER?

TAG and phospholipids

22

What is Acyl CoA is made into in the peroxisomes?

Oxidation and plasmalogen

23

What is Acyl CoA is made into in the mitochondria?

Energy via B-oxidation

24

CPT (Carnitine palmytol trasferase I) is inhibited by _______.

Malonyl CoA

25

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)

26

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.

27

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)

28

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.

29

Cis double bonds and B-oxidation

to undergo B-oxidation must be isomerized to trans or reduced

30

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

31

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

32

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

33

Acetyl CoA carboxylase

takes Acetyl CoA and makes Malonyl CoA

34

What kind of FA chains end up in peroxisomal oxidation?

Very-long-chain FA (24-26)

35

What happens in the peroxisomal oxidation?

Similar to B-oxidation generates NADH via B-oxidation.

36

Similar to B-oxidation generates NADH via B-oxidation.

An oxidase, it makes peroxide which is neutralized by catalase.

37

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

38

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.

39

Where does microsomal w-oxidation occure?

ER enzymes

40

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.

41

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.

42

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

43

Acetoacetyl CoA

reacts with Acetyl CoA with the enzyme HMG-synthase to make HMG-CoA

44

Acetoacetate

is a ketone body (50% of the) product when HMG looses the Acetyl CoA. Acetoacetate spontaneously converts to Acetone

45

D-B-hydroxybutarate

the other 50% of the ketone bodies made, can be made into acetoacetate by a dehydrogenase

46

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

47

What are the amino acids that can generate ketone bodies?

Leucine, isoleucine, tryptophan, phenylalanine and tyrosine

48

When would acetoacetyl be activated to acetoacetyl CoA in the Cytosol?

During cholesterol synthesis

49

When is cytosolic acetyl CoA needed?

ACH in neurons

50

What cells can use ketone bodies?

All including (crossing placenta) except RBC and liver