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
Where does the initial reaction of FA synthesis take place?
cytosol
26
Where does FA elongation and desaturation occur?
microsomes
27
What are the main tissues that can perform FA synthesis?
liver, kidney, brain, lung, mammary gland, adipose
28
What is the initial rxn & rate limiting step of FA synthesis?
Acetyl CoA - malonyl CoA via acetyl CoA carboxylase
29
each reduction step of FA synthesis elongation requires what cofactor?
NADPH
30
What are the 3 NADPH generators that can supply FA synthesis?
-HMS -Isocitrate dehydrogenase -Malate dehydrogenase
31
what is the key regulatory enzyme in lipgenesis?
acetyl-CoA carboxylase
32
What allosterically activates Acetyl CoA carboxylase?
citrate
33
What allosterically inhibits acetyl CoA carboxylase?
long chain fatty acyl CoA (activated form of LCFA, the first step of beta oxidation)
34
Explain how insulin and glucagon regulate lipogenesis
-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
What is the primary source of NADPH needed for lipogenesis?
HMS
36
What is a substantial source of NADPH in ruminants?
isocitrate dehydrogenase
37
What are the non ruminant sources of acetyl CoA
-ketogenic AA -acetyl CoA formation from pyruvate
38
What is the role of citrate in lipogenesis?
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
What are the ruminant sources of acetyl CoA
ruminants produce volatile fatty acids (propionate, acetate, and butyrate), acetate converts to acetyl CoA in the cytosol and can be used for lipogenesis
40
Where does fatty acid elongation occur?
microsomes
41
What is the acetyl donor in FA elongation?
malonyl CoA
42
What is the enzyme needed for FA elongation?
fatty acid elongase