Chapter 26: Fatty Acid and Triacylglyceride Biosynthesis Flashcards
1
Q
In FA biosynthesis, Acetyl-SCoA
A
- Exits the mitochondria
2
Q
FA synthesis takes place in the
A
- Cytoplasm
3
Q
Triacylglyceride synthesis components
A
- Hepatocyte TAG synthesis
- Adipocyte TAG synthesis
- Intestinal epithelium TAG synthesis
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
5
Q
Committed step of FA biosynthesis is catalyzed be
A
- Acetyl-CoA carboxylase
6
Q
In the fed state (presence of insulin) carbohydrates can be converted to
A
- Fats
- Glycolysis is on
7
Q
In the fed state while glycolysis is on, pyruvate is
A
- Pyruvate is being produced and converted to Acetyl coenzyme A
8
Q
Carbon units from glucose have reducing power from
A
- NADPH (from PPP)
- Using reducing equivalents from NADH to make fatty acids
9
Q
FA synthesis is catalyzed by a
A
- Fatty acid synthase complex
10
Q
Pathway intermediates remain attached to
A
- An acyl carrier protein on the FA synthase complex
11
Q
ACP
A
- Codes for a carrier protein
- Part of the fatty acid synthase complex
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
13
Q
Fatty acyl-ACP will hold the growing FA chain until it contains
A
- 16 carbon units
14
Q
Malonyl-Coenzyme A is a
A
- 3 carbon molecule
15
Q
Beta oxidation occurs in the
A
- Mitochondria
16
Q
Beta oxidation
A
- Process of breaking down fatty acids
- 2 carbon units at a time
- Generates FADH2 and NADH during process
17
Q
Acetyl-SCoA is formed in the
A
- Mitochondria
18
Q
To take part in FA synthesis, acetyl-SCoA must pass into
A
- The cytosol
- Passes through disguised as citrate
19
Q
Citrate is formed
A
- In the mitochondrial matrix from Acetyl-SCoA and OAA
20
Q
Citrate diffuses across the IMM via
A
- Transcarboxylate transport protein
21
Q
Citrate in the cytoplasm is cleaved into
A
- Acetyl-SCoA and OAA
- Occurs by ATP-citrate lyase (stimulated by insulin)
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)
23
Q
Malic enzyme also produces
A
- NADPH
24
Q
Pyruvate can also enter
A
- The mitochondria
25
FA synthesis starts with the formation of
- Malonyl-SCoA from now cytoplasmic acetyl-SCoA
26
Acetyl-SCoA carboxylase 1
- 2 step reaction that requires biotin and ATP
| - Irreversible carboxylation
27
Irreversible carboxylation reaction serves as
- An activated 2C donor
28
The malonyl-SCoA formed in the A-CoA carboxylase 1 reaction can be utilized in
- Subsequent steps of fatty acid synthesis
29
Acetyl-SCoA 1 commits
- Acetyl-SCoA to fatty acid biosynthesis
| - Metabolically irreversible carboxylation
30
A-CoA carboxylase 1 requires
- Hydrolysis of ATP
| - Biotin cofactor
31
A-CoA carboxylase 1 exhibits
- Ping-pong kinetics
- Active as a polymer
- Inactive as a monomer
32
A-CoA carboxylase 1 is tightly controlled and requires
- Citrate as an activator
33
A-CoA carboxylase 1 is inhibited by
- AMP
- Palmitoyl-CoA
- Slowed my malonyl-CoA (reaction product)
34
A-CoA carboxylase 1 is inactivated by
- Phosphorylation at a specific serine residue (79)
35
Inactivation of A-CoA carboxylase 1 occurs by
- AMP-dependent protein kinase
| - Protein Kinase A (stimulated by glucagon/epinephrine)
36
Inhibition of A-CoA carboxylase 1 by phosphorylation (glucagon) favors
- Monomeric form
37
Active A-CoA carboxylase 1 enzyme form is a
- Polymer
38
Inactive A-CoA carboxylase 1 enzyme form is a
- Monomer
39
Mammalian fatty acid synthase complex
- Large protein
- Homodimeric enzyme complex
- Two -SH groups that hold substrates during the process of FA synthesis
40
Large protein size of FA synthesis complex
- Approximate molecular weight of 500kD
41
Homodimeric enzyme complex (FA synthase complex) catalyzes
- Catalyzes 7 steps in FA biosynthesis
| - i.e. enzyme has 7 catalytic (domains) activities
42
Initiation/elongation of FA synthesis requires
- Formation of acetyl-ACP and malonyl-ACP
43
Condensation (2b) forms
- Acetoacetyl-ACP attached to the enzyme complex
44
Acetoacetyl-ACP is reduced (3) to
- An alcohol
| - D-B-hydroxybutyryl-ACP
45
Water is removed from the hydroxyl group and the neighboring C in dehydration (4) forming
- A double bond in crotonyl-ACP (a-B-trans-butenoyl-ACP)
46
The final step in the elongation process
-
47
The final step in the elongation process
-
48
The product of the first round of the cycle is
- Butyryl-ACP
49
Butyryl-ACP (4C unit) can reenter the cycle with
- Further addition of 2C units (from malonyl-CoA)
| - Ultimately forming palmitate (16C)
50
When fatty acid reaches 16C's in length (palmitate)
- The fatty acyl group is removed by thioesterase (6)
51
We can produce fatty acids longer than 16C's by these two mechanisms in eukaryotes
- Microsomal
- Mitochondrial
- Both require activation (producing CoA derivative)
52
The desaturase system introduces
- Double bonds
53
Desaturase system is found in
- Liver microsomes
54
Essential fatty acids that cannot be synthesized
- Alpha-linolenic acid (omega-3 cardioprotective)
| - Linolenic acid (omea-6 precursor of arachidonic acid)
55
Fatty acids are most often found in cells as
- Triacylglycerides
56
Triacylglycerides are
- Triple esters between glycerol and 3 fatty acids
57
Triacylglycerol synthesis occurs in
- Most tissues
58
Hepatocyte triacylglycerol synthesis occurs in
- The membrane of the ER
| - Via triacylglycerol synthetase complex
59
Glycerol is first converted to
- Glycerol-3-phosphate by glycerokinase
60
Glycerol-3-phosphate is acylated at _____ by _____
- C1
- C2
- By glycerophosphate acyl transferase
61
Adipose tissue does not contain
- Glycerokinase
62
Dietary triacylglyerides are digested in the gut by
- The action of pancreatic lipase
| - Small protein cofactor, co-lipase
63
Triacylglycerides are degraded in the small intesyine by
- Lipase activity
| - The products are absorbed
64
Shorter chain fatty acids are directly absorbed into the
- Portal vein
65
Shorter chain fatty acids travel around the body bound to
- Albumin
66
Longer chain fatty acids (most of our fatty acids) are packaged in
- Chylomicrons
67
Chylomicrons enter the
- Lymphatic system
| - Join circulation later on at the thoracic duct
68
Fatty acid synthesis chain termination (stops elongation) occurs via
- Deacylation
69
Microsomal chain elongation mechanism
- Endoplasmic reticulum
| - Malonyl-SCoA & NADPH
70
Mitochondrial chain elongation system
- Reversal of beta oxidation
- Uses acetyl-SCoA
- Uses NADPH at final step
71
In the liver, stored triacylglycerides are used to
- Synthesize blood lipoproteins (VLDL)
72
In adipose tissue, the triacylglycerides are
- Continuously synthesized, stored, and degraded
73
Different activation mechanisms for glycerol to glycerol-3-phosphate exist in
- Adipocytes
| - Hepatocytes
74
Acylation of G3P by glycerophosphate acyl transferase uses/forms
- Uses acyl CoA
| - Forms phosphatidate
75
In most cases, the fatty acyl chain attached to C1 is _____ and that attached to C2 is _____
- Saturated
| - Unsaturated
76
Phosphatidic acid phosphatase removes
- The phosphate to give DAG
77
DAG is acylated at C3 by
- Diacylglycerol acyl transferase
| - Forms triacylglycerol
