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MCM - Molecular and Cellular Mechanisms) > Fatty Acid Metabolism > Flashcards

Fatty Acid Metabolism Flashcards

1
Q

Sources of fatty acids

A

Diet and synthesis in the liver in the fed state

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2
Q

Major biological roles

A

post-translational modification, energy, membrane composition, hormones, and intracellular messenger

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3
Q

Fatty acid and triacylglycerol synthesis occur in:

A

Cytoplasm (oxidation in the mitochondria)

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4
Q

The true starting material for fatty acid synthesis

A

Citrate (TCA cycle intermediate)

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5
Q

Acetyl CoA is converted to _____ by _____

A

Malonyl CoA
Acetyl CoA Carboxylase (ACC) - Rate limiting enzyme, irreversible step

Requires NADPH
Regulates fatty acid synthesis

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6
Q

Malonyl CoA enters

A

Fatty acid synthase (FAS) which is used to synthesize palmitate form ACP and Vitamin B 5

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7
Q

Acetly CoA can not be trasnported through the mitochondrial membrane so:

A

It is converted to citrate

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8
Q

Citrate shuttle

A

Acetyl CoA is condensed with oxaloacetate to form citrate in the mito matrix

Citrate travels to the cytosol via citrate shuttle where it is converted back to Acetyl CoA and Oxaloacetate using the enzyme citrate lyase

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9
Q

Acetyl CoA conversion to MalonylCoA requires:

A

Acetly CoA carboxylase and

ABC:
ATP
Biotin
CO2

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10
Q

NADPH comes from:

A

PPP and malate to pyruvate conversion which requires malic enzyme

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11
Q

__ NADPH equivalents are required for ____ carbon acetate units added

A

2, 2

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12
Q

Fatty Acid Synthase (FAS)

A

Synthesizes palmitate from Malonyl CoA

It contains Acyl Carrier Protein (ACP)

Has cysteine residues at active site

Requires B5

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13
Q

Net reaction for FAS cycle

A

8 acetyl CoA + 7 ATP + 14 NADPH + 14 H+ –> Plamitate + 8 CoASH + 7 ADP + 7 Pi + 14 NADP+ + 6H20

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14
Q

Elongation

A

performed by elongases

adds 2 C sequentially

Requires NADPH

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15
Q

Initial elongation converts _____ to ______

A

Palmitate to Stearate

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16
Q

Desaturation

A

Desaturases

Adds double bonds

Requires O2, NADH and cytochrome b5

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17
Q

Linoleic and linolenic acids are used to synthesize

A

Arachidonic acid which is the precursor for eicosanoids

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18
Q

Allosteric regulation of ACC

A

Citrate - feed forward activation

Palmitoyl CoA - feed back inhibition

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19
Q

High AMP levels

A

Inhibits ACC through phosphorylation using AMPK

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20
Q

____ and ____ inhibit Acetyl CoA carboxylase (ACC) by ____

A

Glucagon and epinephrine

Phosphorylation

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21
Q

_____ deactivates Hormone sensitive lipase by _____

A

Insulin

activating phosphatase which dephosphorylates Hormone-sensitive lipase

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22
Q

_____ inhibits carnitine acyltransferase 1 (CAT1)

A

Malonyl CoA

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23
Q

Inhibition of Acetyl CoA carboxylase promotes ______ of fatty acids

A

Oxidation

24
Q

Deficiency of essential fatty acids causes

A

Dermatitis and poor wound healing

25
Q

Excess of fatty acids causes

A

Resynthesis of triacylglycerol and storage in fat droplets - produces fatty liver

26
Q

_____ are the major energy reserve in the body

They are never use by these two systems in the body:

A

Triglycerides

Brain and RBCs

27
Q

Rate limiting step in the oxidation of fatty acids

A

carnitine palmitoyl-transferase-1 - for palmitate only (carnitine acyltransferase 1)

Transports fatty acids to the mitochrondrial matrix for oxidation

28
Q

beta-oxidation of fattyl acyl CoA produces

A

Acetly CoA, NADH, FADH2

29
Q

Fatty acids which requires carnitine to be shuttled into _______

A

Long chain fatty acid

Mitochondria

30
Q

Fatty oxidation in the _____ is ________

A

liver, unregulated

31
Q

The only point of regulation of fatty oxidation with _____ is

A

hormones

hormone sensitive lipase in the fat cells

32
Q

The brain adapts to the use of ketone bodies during fasting state by:

A

Converting them to the to glucose for energy

33
Q

non ketotic hypoglycemia is caused by

A

Deficiencies in fatty acid oxidation lead to

34
Q

Fat metabolism in fasted state

General overview

A

low insulin to glucagon ratio causes fatty acid release from adipose

triglycerides are degraded to fatty acids and glycerol (by Hormone-sensitive lipase) and sent to liver and energy requiring tissues

Free fatty acids carried to blood stream and bound to albumin

FAs dissociate from albumin and are transported into cell

35
Q

Hormone sensitive lipase allosteric effectors (in triglycerol degradation)

A

Insulin (-)

Epinephrine, GH (+)

36
Q

Carnitine shuttle

A

Transports ≥ 14 C FAs to mito membrane

Carnitine acyltransferase I - outer surface of inner membrane of mito (rate limiting)

Translocase - transports conjugates across inner membrane

Carnitine acyltransferase II - inner surface of inner membrane - carnitine –> fatty acyl CoA

37
Q

Beta-oxidation is the ______ of synthesis

A

reversal

38
Q

beta-oxidation summary:

A

Palmitoly CoA + 7 CoA + 7 FAD + 7 NAD + 7 H2O –> 8 acetyl CoA + 7 FADH2 + 7 NADH + 7 H+

Palmityl CoA under goes 7 rounds of b-oxidation

39
Q

ATP produced from beta-oxidation of palmitoyl CoA

A

106

40
Q

Major difference betwenn odd and even fatty acid metabolism

A

succinyl CoA is used as a substrate for gluconeogenesis and Acetyl CoA is not

41
Q

Very Long Chain Fatty Acids (VLCA)

A

can not enter the mitochondrial matrix so are oxidized to short and medium chain FAs in the peroxisome

42
Q

alpha-oxidation of BCFAs

A

Required for metabolism of plants

43
Q

Unsaturated fatty acids

A

Enoyl CoA Isomerase moves cis double bond to trans double bond

44
Q

MCAD Deficiency

A

Defect in Medium-chain acyl CoA dehydrogenase

MItochondria

Dixarboxylic acid build up

Vommiting, lethargy, hypoglycemia

45
Q

Methylmalonyl acidemia

A

Defect in methylmalonyl CoA mutase and adenosylcobalamin deficiencies

Progressive encephalopathy, seizures, ketosis, acidosis

46
Q

Odd number fatty acid metabolism

A

Propionyl CoA (propionyl CoA carboxylase - Biotin) > methylmalonyl CoA (methylmalonyl CoA mutase - B12) > Succinyl CoA

Met, Ile and Val also feed into thos reaction to form propionyl CoA

47
Q

Adult refsum disease

A

Deficiency of phytanoyl-CoA hydroxylase
Build up of phytanic acid in peroxisomes

Symptoms- neuropathy, cerebellar ataxia, shoretning of 4th toe and hearing loss

48
Q

Odd chain fatty acid oxidation

A

Odd chain fatty acid OR Met, Ile, Val –> Propionyl CoA (by propionly CoA carboxylase) –> Methylmalonyl CoA (by methymalonyl CoA mutase) –> Succinyl CoA –> TCA cycle

49
Q

Even chain fatty acid oxidation

A

Palmitate –> Acyl CoA (by fatty acyl CoA synthetase) –> Acyl carnitine (by carnitine palmitolyl trasnferase I) –> Acyl CoA (by Acyl CoA dehydrogenase/medium chain Acyl CoA dehydrogenase) –> trans enoyl CoA –> Acetyl CoA –> CO2 or Ketone Bodies

50
Q

Fatty Acyl CoA synthetase uses:

A

ATP and Coenzyme A

51
Q

Carnitine palmitoyl transferase 1 or (CAT 1) uses:

A

Carnitine

52
Q

Palmitate is a ___ C FA

A

16

53
Q

Rate limiting step of fatty synthesis and its allosteric effectors

A

Acetly CoA Carboxylase

+Citrate - feed forward activation

Activator:
Insulin

-Palmitoyl CoA - feed back inhibition

Inhibitor:
Glucagon
Epinephrine
AMP

54
Q

Rate limiting step of fatty oxidation and its allosteric effectors

A

Carnitine Acyl Transferase I

Malonyl CoA

55
Q

Hormone sensitive lipase is important in

A

triglycerol degradation

56
Q

_____ activates Hormone sensitive lipase by _____

A

Norepinephrine and epinephrine

phosphorylation

57
Q

Insulin does what to ACC?

A

Activates it through dephosphorylation

MCM - Molecular and Cellular Mechanisms) (6 decks)

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