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MCD Metabolism > metabolic pathways and ATP production > Flashcards

metabolic pathways and ATP production Flashcards

fatty acid metabolism: summarise the pathways for the synthesis and metabolism of fatty acids with respect to the substrates and products, coenzymes used, carrier molecules and their cellular locations; explain how inborn errors of fatty acid metabolism may cause disease

1
Q

structure of a fatty acid

A

hydrophilic COO- head and hydrophobic hydrocarbon tail

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2
Q

saturated vs unsaturated fatty acid

A

saturated have no C=C and are solid; unsaturated have C=C present and are liquid

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3
Q

enzyme for desaturation

A

fatty acyl CoA desaturase

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4
Q

where is fat obtained

A

diet, liver (de novo), adipocytes

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5
Q

what does bile do

A

emulsify fats and increase their digestion and absorption

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6
Q

what is steatorrhea and how is it used to treat obesity

A

fatty stool; inhibit lipases

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7
Q

where does B-oxidation occur

A

mitochondria

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8
Q

sources of fatty acids

A

triacylglycerols, adipose

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9
Q

fatty acid to acyl CoA reaction

A

fatty acid + ATP + HSCoA → acyl CoA + AMP + PPi

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10
Q

what enzyme catalyses the conversion of fatty acids to acyl CoA, and where in the mitochondria does it act

A

acyl CoA synthase in outer membrane

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11
Q

how is acyl CoA transported into the matrix

A

via coupling to carnitine and entering via a translocase membrane

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12
Q

reaction of acyl CoA with carnitine, and enzyme

A

acyl CoA + carnitine ⇌ acyl carnitine, by carnitine acyltransferases

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13
Q

diagram of translocase

A

diagram from metabolism 6

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14
Q

acyl CoA → acetyl CoA: first step

A

acyl CoA oxidised by dehydrogenase enzyme (FAD → FADH2)

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15
Q

acyl CoA → acetyl CoA: second step

A

hydrated by hydrolase enzyme

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16
Q

acyl CoA → acetyl CoA: third step

A

oxidised by dehydrogenase enzyme (NAD+ → NADH + H+)

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17
Q

acyl CoA → acetyl CoA: fourth step

A

cleavage by reacting with HSCoA, catalysed by thiolase enzyme to form acetyl CoA and an acyl CoA

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18
Q

how many fewer carbons does the new acyl CoA have

A

2

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19
Q

acetyl CoA formation diagram

A

diagram from metabolism 6

20
Q

palmitoyl as example of fatty acid: reaction

A

palmitoyl CoA + 7 FAD + 7 NAD+ + 7 H2O + 7 CoA → 8 acetyl CoA + 7 FADH2 + 7 NADH

21
Q

how many B-oxidations required for palmitoyl

A

7 (16C → 8 acetyl CoA as last produces 2x acetyl CoA, as 4C intermediate)

22
Q

what is the maximum number of ATP molecules produced by palmitoyl B-oxidation

A

129 ATP as 131 but 2 bonds broken: ATP → AMP+PPi

23
Q

why can’t glucose be generated via gluconeogenesis in this pathway

A

pyruvate is not produced when fats are respired, so there is no conversion to oxaloacetate, so [oxaloacetate] decreases; therefore acetyl CoA from B-oxidation only enters TCA if balanced with carbohydrate metabolism

24
Q

what happens to acetyl CoA when B-oxidation is greater than glycolysis (e.g. when fasting)

A

converted to ketone bodies in the liver

25
Q

fat metabolism diagram

A

diagram from metabolism 9

26
Q

acetyl CoA → fatty acid (lipogenesis): what enymes are required and where does it occur

A

acetyl CoA carboxylase and fatty acid synthase (FAS); occurs in cytoplasm

27
Q

list the components associated with FAS

A

synthesising, transferring, dehydrating, reducing and hydrolysing; also contains acyl carrier protein (ACP), which is a swinging arm to move molecules (similar to PDH)

28
Q

acetyl CoA → fatty acid (lipogenesis): first stage

A

formation of malonyl CoA by acetyl CoA carboxylase (+ HCO3-) and biotin coenzyme; ATP → ADP + Pi

29
Q

acetyl CoA → fatty acid (lipogenesis): second stage

A

transfer of malonyl to ACP ro form malonyl-ACP (ACP → HSCoA)

30
Q

acetyl CoA → fatty acid (lipogenesis): third stage

A

transfer of acetyl from acetyl CoA to ACP to form acetyl-ACP (ACP → HSCoA)

31
Q

acetyl CoA → fatty acid (lipogenesis): fourth stage

A

condensation of malonyl-ACP and acetyl-ACP to form 4C fatty acid acetoacetyl-ACP

32
Q

acetyl CoA → fatty acid (lipogenesis): fifth stage

A

reduction of acetoacetyl-CoA to 3-hydroxybutyryl-ACP (NADPH → NADP+)

33
Q

acetyl CoA → fatty acid (lipogenesis): sixth stage

A

dehydration of 3-hydroxybutyryl-ACP to crotonyl-ACP

34
Q

acetyl CoA → fatty acid (lipogenesis): seventh stage

A

reduction of crotonyl-ACP to butyryl-ACP (NADPH → NADP+)

35
Q

how many times must stages 4 to 7 be repeated to form 16C palmitoyl-ACP

A

6

36
Q

final stage reaction of acetyl CoA → fatty acid (lipogenesis) for palmitate

A

hydrolysis of palmitoyl-ACP to palmitate and ACP

37
Q

summary reaction of acetyl CoA → palmitate (lipogenesis)

A

acetyl CoA (C2) + 7 malonyl CoA (C3) + 14 NADPH + 14 H+ → palmitate (C16) + 7CO2 + 6H2O + 8CoA-SH + 14 NADP+

38
Q

how many more carbons does the fatty acid have

A

2

39
Q

B-oxidation vs lipogenesis reaction sequences

A

B-oxidation: oxidation, hydration, oxidation, cleavage; lipogenesis: condensation, reduction, dehydration, reduction

40
Q

diagram showing B-oxidation and lipogenesis differences

A

diagram from metabolism 6

41
Q

B-oxidation and lipogenesis: difference in carriers

A

B-oxidation: CoA; lipogenesis: ACP

42
Q

B-oxidation and lipogenesis: difference in reducing power

A

B-oxidation: NADPH; lipogenesis: FAD/NAD+

43
Q

why is a family of acyl CoA dehydrogenases required

A

catalyse different lengths of fatty acids (fatty acids pocessed produce acyl CoA with 2 fewer carbons)

44
Q

inborn disorders of fatty acid oxidation: MCAD deficiency

A

C6-C12; can’t break down FA beyond C6 so can’t generate acetyl CoA; can be fatal (especially if fasting); treated with a high carb diet and IV glucose

45
Q

inborn disorders of fatty acid oxidation: primary carnitine deficiency

A

mutation in gene for carnitine transporter which lowers carnitine uptake; treated with carnitine supplements

MCD Metabolism (21 decks)

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