FA Metabolism Flashcards

1
Q

Nomenclature for double bonds

A

Number corresponds to number of carbons away from carbonyl carbon, inclusive

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2
Q

Most common saturated FA

A

Palmitic acid

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3
Q

Most common unsaturated FA

A

Oleic acid

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4
Q

Overview

A

Glycerol-3P is created from DHAP, then combined with free FA’s to create triglycerides

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5
Q

Where is Triglyceride stored?

A

In adipose tissue, for use of other tissues

In muscle, for its own use

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6
Q

What is the result of an overflow of excess lipids

A

Lipids begin to be stored in other tissues, such as the liver and muscle leading to insulin resistance

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7
Q

What breaks down TG to DAG?

A

Adipose Triglyceride Lipase

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8
Q

What breaks down DAG to MAG?

A

Hormone Sensitive Lipase

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9
Q

What breaks down MAG to glycerol and free FA?

A

MAG Lipase

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10
Q

Which hormones stimulate lipolysis?

A

Epinephrine, Glucagon

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11
Q

3 macro steps of FA breakdown

A

1) Acylation of FA’s via acyl-CoA
2) Transport into mitochondria via Carnitine shuttle
3) ß-oxidation

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12
Q

What is special about acyl-CoA synthase in terms of energy?

A

It uses ATP which gets converted into AMP and PPi because the bond is so high-energy, which allows the reaction to be pulled to the right

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13
Q

Describe the Carnitine shuttle

A

CPT-1 combines Acyl-CoA with Carnitine to produce fatty acyl-carnitine, which is then transported across the IMM by Translocase

CPT-II splits fatty acyl-carnitne into Acyl-CoA and Carnitine which is cycled back out

CPT = Carnitine Palmitoyl Transferase

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14
Q

First step of beta-oxidation

A

Acyl-CoA to trans-∆2-enoyl-CoA via Acyl CoA DH

FAD -> FADH2
Feeds into ETC

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15
Q

Second step of beta-oxidation

A

trans-∆2-enoyl-CoA to L-3-hydroxyacyl-CoA

via Enoyl-CoA hydratase

Input of H2O

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16
Q

Third step of beta-oxidation

A

L-3-hydroxyacyl-CoA to 3-Ketoacyl-CoA

via L-3-hydroxyacyl-CoA DH

NAD to NADH
Feeds into ETC

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17
Q

Fourth step of beta-oxdation

A

3-Ketoacyl-CoA to Acyl-CoA + Acetyl-CoA

via ß-ketothiolase

Input of CoA

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18
Q

Inhibition of Carnitine shuttle via Malonyl-CoA

A

ACC (acetyl-CoA carboxylase) creates Malonyl-CoA (inhibitory)

Inhibition of ACC via AMPK/PKA signals a low-energy state and stopping of FA synthesis

Prevention of Malonyl-CoA synthesis, resulting in de-inhibiton of Carnitine shuttle

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19
Q

AMPK

A

AMP-activated protein kinase

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20
Q

Describe MCAD

A

Medium-chain Acyl-CoA DH deficiency (first step in ß-oxidation)

Hypoglycemia
- no FA oxidation, so glucose used up
- no FA, so no gluconeogenesis

21
Q

Ketone body pathway synthesis first step

A

2 Acetyl-CoA via Thiolase to Acetoacetyl-CoA

22
Q

Ketone body pathway synthesis second step

A

Addition of another Acetyl-CoA to produce HMG-CoA via HMG-CoA synthase

23
Q

Ketone body pathway synthesis third step

A

Loss of acetyl-CoA produces acetoacetate

24
Q

Ketone body pathway synthesis fourth step

A

Acetoacetate can produce acetone and D-3-Hydrozybutyrate (all ketone bodies) via DH

25
Q

Ketone body breakdown first step

A

D-3-Hydroxybutyrate via DH to Acetoacetate

26
Q

Ketone body breakdown second step

A

Acetoacetate to Acetoacetyl-CoA via Succinyl-CoA to Succinate

enzyme is transferase

27
Q

Ketone body breakdown third step

A

Acetoacetyl-CoA to 2x Acetyl-CoA via Thiolase

28
Q

Diabetic Ketoacidosis

A

T1D - decreased insulin, increased epinephrine and glucagon trigger mass lipolysis

This puts many FA’s into circulation, which are broken down into ACetyl-CoA

Leads to mass production of ketone bodies (H+ is a byproduct, creating acidosis)

29
Q

FA synthesis differences to oxidation

A

1) All in cytoplasm
2) Reactants attached to ACP
3) FAS complex
4) Uses NADPH

30
Q

FA synthesis step one

A

Acetyl-CoA to Malonyl-CoA by Acetyl-CoA carboxylase

31
Q

FA synthesis step two

A

Attachment of ACP

Transacylase

32
Q

FA synthesis step three

A

Condensation step of acetyl and malonyl ACP to create acetoacetyl-ACP via Condensing enzyme

Loss of ACP and CO2

33
Q

FA synthesis step four

A

Reduction via reductase to D-3-Hydroxybutyryl-ACP

NADPH to NADP

34
Q

FA synthesis step five

A

Dehydration of D-3-Hydroxybutyryl-ACP to Crotonyl-ACP

35
Q

FA synthesis step six

A

Reduction of Crotonyl-ACP to Butyryl-ACP

NADPH to NADP

36
Q

FA synthesis after 16C

A

Hydration of Palmitoyl-ACP to Palmitic Acid via Thioesterase

37
Q

Overall reaction for Palmitate synthesis

A

8 Acetyl CoA + 14 NADPH + 7 ATP

38
Q

Where do the NADPH for FA synthesis come from?

A

8 from Citrate Pyruvate shuttle
6 from PPP

39
Q

Which enzymes are part of Fatty Acid Synthase?

A

All of them except for Acetyl-CoA Carboxylase

40
Q

Acetyl-CoA Carboxylase inhibitors and activators

A

Inhibitor: long chain acyl-CoA and PKA/AMPK

Activator: Citrate

41
Q

Goal of the Citrate-Pyruvate shuttle

A

Bring Acetyl-CoA into the cytoplasm for FA synthesis, and produce NADPH

42
Q

Citrate-Pyruvate shuttle mechanism

A

OAA + Acetyl-CoA -> Citrate -> OAA -> Malate -> Pyruvate -> OAA

43
Q

Which enzyme releases Acetyl-CoA in the cytosol for FA synthesis?

A

Citrate to OAA via ATP-Citrate Lyase

44
Q

Which enzyme reoxidizes NADP in the cytosol for FA synthesis?

A

Malic enzyme converts Malate to Pyruvate and produces NADPH

45
Q

FA elongation

A

Process of extending Palmitic acid up to 24 C using Malonyl CoA and NADPH

46
Q

FA desaturation

A

Uses desaturases to remove carbon atoms

47
Q

What are essential fatty acids

A

Linoleic and Linolenic acid must be supplied in the diet because double bonds cannot be synthesized beyond C9

48
Q

Source of glycerol for TAGs

A

DHAP and phosphorylation of glycerol by glycerol kinase (liver)