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Biochemistry I > Chapter 26: Fatty Acid and Triacylglyceride Biosynthesis > Flashcards

Chapter 26: Fatty Acid and Triacylglyceride Biosynthesis Flashcards

1
Q

In FA biosynthesis, Acetyl-SCoA

A
  • Exits the mitochondria
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2
Q

FA synthesis takes place in the

A
  • Cytoplasm
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3
Q

Triacylglyceride synthesis components

A
  • Hepatocyte TAG synthesis
  • Adipocyte TAG synthesis
  • Intestinal epithelium TAG synthesis
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4
Q

FA biosynthesis components

A
  • Acetyl-SCoA exits mitochondria
  • Production of malonyl-SCoA
  • FA synthesis complex
  • Initiation, elongation (repeat of cycle)
  • Termination
  • Chain elongation mechanisms
  • FA denaturation
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5
Q

Committed step of FA biosynthesis is catalyzed be

A
  • Acetyl-CoA carboxylase
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6
Q

In the fed state (presence of insulin) carbohydrates can be converted to

A
  • Fats

- Glycolysis is on

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7
Q

In the fed state while glycolysis is on, pyruvate is

A
  • Pyruvate is being produced and converted to Acetyl coenzyme A
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8
Q

Carbon units from glucose have reducing power from

A
  • NADPH (from PPP)

- Using reducing equivalents from NADH to make fatty acids

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9
Q

FA synthesis is catalyzed by a

A
  • Fatty acid synthase complex
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10
Q

Pathway intermediates remain attached to

A
  • An acyl carrier protein on the FA synthase complex
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11
Q

ACP

A
  • Codes for a carrier protein

- Part of the fatty acid synthase complex

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12
Q

When a fatty acid chain is growing, it grows

A
  • Sequential addition of 2 carbon units at a time

- 2C units are in the form of malonyl-ACP from acetyl-SCoA

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13
Q

Fatty acyl-ACP will hold the growing FA chain until it contains

A
  • 16 carbon units
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14
Q

Malonyl-Coenzyme A is a

A
  • 3 carbon molecule
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15
Q

Beta oxidation occurs in the

A
  • Mitochondria
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16
Q

Beta oxidation

A
  • Process of breaking down fatty acids
  • 2 carbon units at a time
  • Generates FADH2 and NADH during process
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17
Q

Acetyl-SCoA is formed in the

A
  • Mitochondria
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18
Q

To take part in FA synthesis, acetyl-SCoA must pass into

A
  • The cytosol

- Passes through disguised as citrate

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19
Q

Citrate is formed

A
  • In the mitochondrial matrix from Acetyl-SCoA and OAA
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20
Q

Citrate diffuses across the IMM via

A
  • Transcarboxylate transport protein
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21
Q

Citrate in the cytoplasm is cleaved into

A
  • Acetyl-SCoA and OAA

- Occurs by ATP-citrate lyase (stimulated by insulin)

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22
Q

For OAA to return to the mitochondria, it must

A
  • First be reduced to malate (catalyzed by MDH in the cytosol)
  • Theh malate oxidatively decarboxylated to pyruvate (by the NADP+ linked malic enzyme)
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23
Q

Malic enzyme also produces

A
  • NADPH
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24
Q

Pyruvate can also enter

A
  • The mitochondria
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25
Q

FA synthesis starts with the formation of

A
  • Malonyl-SCoA from now cytoplasmic acetyl-SCoA
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26
Q

Acetyl-SCoA carboxylase 1

A
  • 2 step reaction that requires biotin and ATP

- Irreversible carboxylation

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27
Q

Irreversible carboxylation reaction serves as

A
  • An activated 2C donor
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28
Q

The malonyl-SCoA formed in the A-CoA carboxylase 1 reaction can be utilized in

A
  • Subsequent steps of fatty acid synthesis
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29
Q

Acetyl-SCoA 1 commits

A
  • Acetyl-SCoA to fatty acid biosynthesis

- Metabolically irreversible carboxylation

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30
Q

A-CoA carboxylase 1 requires

A
  • Hydrolysis of ATP

- Biotin cofactor

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31
Q

A-CoA carboxylase 1 exhibits

A
  • Ping-pong kinetics
  • Active as a polymer
  • Inactive as a monomer
32
Q

A-CoA carboxylase 1 is tightly controlled and requires

A
  • Citrate as an activator
33
Q

A-CoA carboxylase 1 is inhibited by

A
  • AMP
  • Palmitoyl-CoA
  • Slowed my malonyl-CoA (reaction product)
34
Q

A-CoA carboxylase 1 is inactivated by

A
  • Phosphorylation at a specific serine residue (79)
35
Q

Inactivation of A-CoA carboxylase 1 occurs by

A
  • AMP-dependent protein kinase

- Protein Kinase A (stimulated by glucagon/epinephrine)

36
Q

Inhibition of A-CoA carboxylase 1 by phosphorylation (glucagon) favors

A
  • Monomeric form
37
Q

Active A-CoA carboxylase 1 enzyme form is a

A
  • Polymer
38
Q

Inactive A-CoA carboxylase 1 enzyme form is a

A
  • Monomer
39
Q

Mammalian fatty acid synthase complex

A
  • Large protein
  • Homodimeric enzyme complex
  • Two -SH groups that hold substrates during the process of FA synthesis
40
Q

Large protein size of FA synthesis complex

A
  • Approximate molecular weight of 500kD
41
Q

Homodimeric enzyme complex (FA synthase complex) catalyzes

A
  • Catalyzes 7 steps in FA biosynthesis

- i.e. enzyme has 7 catalytic (domains) activities

42
Q

Initiation/elongation of FA synthesis requires

A
  • Formation of acetyl-ACP and malonyl-ACP
43
Q

Condensation (2b) forms

A
  • Acetoacetyl-ACP attached to the enzyme complex
44
Q

Acetoacetyl-ACP is reduced (3) to

A
  • An alcohol

- D-B-hydroxybutyryl-ACP

45
Q

Water is removed from the hydroxyl group and the neighboring C in dehydration (4) forming

A
  • A double bond in crotonyl-ACP (a-B-trans-butenoyl-ACP)
46
Q

The final step in the elongation process

A

-

47
Q

The final step in the elongation process

A

-

48
Q

The product of the first round of the cycle is

A
  • Butyryl-ACP
49
Q

Butyryl-ACP (4C unit) can reenter the cycle with

A
  • Further addition of 2C units (from malonyl-CoA)

- Ultimately forming palmitate (16C)

50
Q

When fatty acid reaches 16C’s in length (palmitate)

A
  • The fatty acyl group is removed by thioesterase (6)
51
Q

We can produce fatty acids longer than 16C’s by these two mechanisms in eukaryotes

A
  • Microsomal
  • Mitochondrial
  • Both require activation (producing CoA derivative)
52
Q

The desaturase system introduces

A
  • Double bonds
53
Q

Desaturase system is found in

A
  • Liver microsomes
54
Q

Essential fatty acids that cannot be synthesized

A
  • Alpha-linolenic acid (omega-3 cardioprotective)

- Linolenic acid (omea-6 precursor of arachidonic acid)

55
Q

Fatty acids are most often found in cells as

A
  • Triacylglycerides
56
Q

Triacylglycerides are

A
  • Triple esters between glycerol and 3 fatty acids
57
Q

Triacylglycerol synthesis occurs in

A
  • Most tissues
58
Q

Hepatocyte triacylglycerol synthesis occurs in

A
  • The membrane of the ER

- Via triacylglycerol synthetase complex

59
Q

Glycerol is first converted to

A
  • Glycerol-3-phosphate by glycerokinase
60
Q

Glycerol-3-phosphate is acylated at _____ by _____

A
  • C1
  • C2
  • By glycerophosphate acyl transferase
61
Q

Adipose tissue does not contain

A
  • Glycerokinase
62
Q

Dietary triacylglyerides are digested in the gut by

A
  • The action of pancreatic lipase

- Small protein cofactor, co-lipase

63
Q

Triacylglycerides are degraded in the small intesyine by

A
  • Lipase activity

- The products are absorbed

64
Q

Shorter chain fatty acids are directly absorbed into the

A
  • Portal vein
65
Q

Shorter chain fatty acids travel around the body bound to

A
  • Albumin
66
Q

Longer chain fatty acids (most of our fatty acids) are packaged in

A
  • Chylomicrons
67
Q

Chylomicrons enter the

A
  • Lymphatic system

- Join circulation later on at the thoracic duct

68
Q

Fatty acid synthesis chain termination (stops elongation) occurs via

A
  • Deacylation
69
Q

Microsomal chain elongation mechanism

A
  • Endoplasmic reticulum

- Malonyl-SCoA & NADPH

70
Q

Mitochondrial chain elongation system

A
  • Reversal of beta oxidation
  • Uses acetyl-SCoA
  • Uses NADPH at final step
71
Q

In the liver, stored triacylglycerides are used to

A
  • Synthesize blood lipoproteins (VLDL)
72
Q

In adipose tissue, the triacylglycerides are

A
  • Continuously synthesized, stored, and degraded
73
Q

Different activation mechanisms for glycerol to glycerol-3-phosphate exist in

A
  • Adipocytes

- Hepatocytes

74
Q

Acylation of G3P by glycerophosphate acyl transferase uses/forms

A
  • Uses acyl CoA

- Forms phosphatidate

75
Q

In most cases, the fatty acyl chain attached to C1 is _____ and that attached to C2 is _____

A
  • Saturated

- Unsaturated

76
Q

Phosphatidic acid phosphatase removes

A
  • The phosphate to give DAG
77
Q

DAG is acylated at C3 by

A
  • Diacylglycerol acyl transferase

- Forms triacylglycerol

Biochemistry I (34 decks)

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