Fatty Acid Oxidation & Synthesis Flashcards

1
Q

True/False: Fatty acid catabolism can be both and aerobic and anaerobic process?

A

false: requires the presence of oxygen

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2
Q

breakdown of free fatty acids occurs in ____ carbon increments?

A

two carbon increments

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3
Q

Where does fatty acid oxidation cleavage occur?

A

between the alpha and beta carbon

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4
Q

Where does fatty acid oxidation primarily occur? what is the exception?

A

the mitochondrial matrix. very long chain fatty acids (>20 carbons) are oxidized in peroxisomes

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5
Q

What are the main target tissues of FA oxidation?

A

muscles, heart, liver, kidney

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6
Q

Explain the process of FFA getting to and entering target cells

A

FFA are bound in serum to ALB, they enter target cells via transporters and are bound in the cell by fatty acid binding proteins

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7
Q

What is the first step of fatty acid oxidation?

A

They have to be converted to an active intermediate before catabolism.

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8
Q

How many ATP does the first step of oxidation require?

A

two

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9
Q

What enzyme is needed for the first step of FA oxidation?

A

Acyl CoA synthetase

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10
Q

Where does FA activation/step 1 occur?

A

cytosol

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11
Q

How does activated FA get transported from the cytosol into the mitochondria?

A

The acyl group of acyl CoA is transferred to carnitine by CPT-1, this allows it cross the inner mitochondrial membrane. Acyl CoA is then reformed by CPT-II

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12
Q

What two amino acids is carnitine synthesized from?

A

lysine and methionine

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13
Q

What two vitamins and mineral is required for carnitine synthesis?

A

vitamin C, pyridoxyl phosphate, and iron

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14
Q

What is the rate limiting step of FA oxidation?

A

CPT-I

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15
Q

Generally describe beta oxidation

A

-after acyl-CoA is transported into the mitochondrial matrix, two carbon subunits are removed as acetyl CoA
-each cycle of oxidation produces one molecule of acetyl CoA, one NADH, and one FADH2

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16
Q

What is a potential fate for post oxidation acetyl CoA

A

it can enter the TCA cycle

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17
Q

What are two variations of FA oxidation?

A

-odd chained: end result is propionyl CoA which can be converted to succinyl CoA and enter the TCA cycle
-unsaturated fatty acids: oxidized as saturated until the first double bond, converted to trans double bond,then can continue as normal

18
Q

how does short and medium chain fatty acid oxidation differ from long chain?

A

short and medium chained fatty acids can cross the inner mitochondrial membrane without carnitine, so once inside they are activated and oxidized as normal

19
Q

What does oxidation in peroxisomes yield? how is it dealt with

A

peroxide, it is neutralized by catalases in the peroxisome

20
Q

Explain the 3 main differences between peroxisomal and mitochondrial FA oxidation

A

-does not require carnitine
-utilizes different enzymes
-oxidases produce FADH2 which is converted to peroxide which is neutralized by catalases

21
Q

What would inhibit the rate limiting enzyme of beta oxidation?

A

malonyl CoA (substrate for fatty acid synthesis)

22
Q

During what state in FA oxidation highest?

A

highest during fasting

23
Q

describe how insulin and glucagon regulate fatty acid oxidation

A

-glucagon stimulates FA oxidation and decreases fatty acid synthesis
-lower insulin levels removes insulin inhibition of hormone sensitive lipase thereby increasing fatty acid mobilization

24
Q

What is the building block of fatty acid synthesis?

A

acetyl CoA

25
Q

Where does the initial reaction of FA synthesis take place?

A

cytosol

26
Q

Where does FA elongation and desaturation occur?

A

microsomes

27
Q

What are the main tissues that can perform FA synthesis?

A

liver, kidney, brain, lung, mammary gland, adipose

28
Q

What is the initial rxn & rate limiting step of FA synthesis?

A

Acetyl CoA - malonyl CoA via acetyl CoA carboxylase

29
Q

each reduction step of FA synthesis elongation requires what cofactor?

A

NADPH

30
Q

What are the 3 NADPH generators that can supply FA synthesis?

A

-HMS
-Isocitrate dehydrogenase
-Malate dehydrogenase

31
Q

what is the key regulatory enzyme in lipgenesis?

A

acetyl-CoA carboxylase

32
Q

What allosterically activates Acetyl CoA carboxylase?

A

citrate

33
Q

What allosterically inhibits acetyl CoA carboxylase?

A

long chain fatty acyl CoA (activated form of LCFA, the first step of beta oxidation)

34
Q

Explain how insulin and glucagon regulate lipogenesis

A

-Insulin activates protein phosphatase which activates acetyl CoA carboxylase by dephosphorylating it.
-glucagon and epinephrine activate AMP dependent kinases that activate AMPK that phosphorylates and inactivates acetyl CoA carboxylase

35
Q

What is the primary source of NADPH needed for lipogenesis?

A

HMS

36
Q

What is a substantial source of NADPH in ruminants?

A

isocitrate dehydrogenase

37
Q

What are the non ruminant sources of acetyl CoA

A

-ketogenic AA
-acetyl CoA formation from pyruvate

38
Q

What is the role of citrate in lipogenesis?

A

citrate can leave the mitochondria and be converted to OAA and acetyl CoA by citrate lyase in the cytosol which provides acetyl CoA as a substrate

39
Q

What are the ruminant sources of acetyl CoA

A

ruminants produce volatile fatty acids (propionate, acetate, and butyrate), acetate converts to acetyl CoA in the cytosol and can be used for lipogenesis

40
Q

Where does fatty acid elongation occur?

A

microsomes

41
Q

What is the acetyl donor in FA elongation?

A

malonyl CoA

42
Q

What is the enzyme needed for FA elongation?

A

fatty acid elongase