1.9 - Fatty Acid Metabolism II (Anabolism)

Question 1

2 stage process of biosynthesis (2)

Answer 1

1. preparation of precursor malonyl-CoA and acyl-ACP
2. elongation of fatty acid by fatty acid synthase

Question 2

starting materials of biosynthesis (2)

Answer 2

1. unit added is malonyl-CoA (instead of acetyl-CoA)
2. chain reaction starts from acyl-CoA and malonyl-CoA

Question 3

primary electron donor of biosynthesis

Answer 3

NADPH

Question 4

where does FA catabolism (B-oxidation) occur?

Answer 4

mitochondria

Question 5

where does FA anabolism (biosynthesis) occur?

Answer 5

cytoplasm

Question 6

1st step of FA biosynthesis (carboxylation)

Answer 6

carboxylation of acetly-CoA to malonyl-CoA by acetyl-CoA carboxylase (requires 1 ATP per malonyl-CoA synthesised)

Question 7

substrates of fatty acid synthase (3)

Answer 7

1. acetly-CoA
2. malonyl-CoA
3. NADPH

Question 8

what encodes mammalian FA synthase

Answer 8

single gene

Question 9

mammalian FA synthase structure

Answer 9

single polypeptide chain with 3 domains and 7 catalytic sites (homodimer)

Question 10

how many FA can FA synthase synthesise simultaneously?

Answer 10

2

Question 11

what is required in a significant quantity for biosynthesis?

Answer 11

NADPH

Question 12

biosynthesis substrate reactions catalysed by FA synthase

Answer 12

condensation -> reduction -> hydration -> reduction

Question 13

how many acetyl-CoA and ATP make malonyl-CoA?

Answer 13

7 acetyl-CoA + 7 ATP -> malonyl-CoA

Question 14

how many acetyl-CoA, ATP, malonyl-CoA and NADPH make palmitate?

Answer 14

1 acetyl-CoA + 7 ATP + 7 malonyl-CoA + 14 NADPH -> palmitate

Question 15

main product of FA biosynthesis

Answer 15

16-carbon fatty acid, palmitate

Question 16

what catalyse elongation reactions of biosynthesis?

Answer 16

enzymes located on cytosolic face of endoplasmic reticulum (ER) membrane

Question 17

donor for elongation reactions of biosynthesis

Answer 17

malonyl-CoA

Question 18

where does FA elongation occur?

Answer 18

endoplasmic reticulum (ER)

Question 19

enzyme required for FA elongation

Answer 19

fatty acid elongase

Question 20

difference between FA elongase activity and FA synthesis (on cytosolic ER membrane)

Answer 20

malonyl-CoA (FA attached to CoA instead of ACP (acyl-carrier protein)

Question 21

role fatty acid production in the brain

Answer 21

very long chain FA produced in brain, increases rapidly during myelination producing FA required for sphingolipid production

Question 22

where are FA biosynthesis pathways present in the body? (3)

Answer 22

1. liver cells
2. brain cells
3. kidney cells

Question 23

what regulates FA biosynthesis?

Answer 23

hormones

Question 24

when is the FA biosynthesis used

Answer 24

conditions of excess energy (particularly carbohydrate intake)

Question 25

what happens when citrate accumulated more than capacity of TCA cycle to process

Answer 25

citrate moves to cytoplasm

Question 26

when is FA biosynthesis active in mammary glands

Answer 26

post pregnancy

Question 27

what happens to excess citrate when it moves to the cytoplasm? (2)

Answer 27

1. citrate digested to acetyl-CoA and oxaloacetate 2. oxaloacetate resturns to mitochondria as pyruvate

Question 28

what does the conversion of oxaloacetate -> malate -> pyruvate provide?

Answer 28

NADPH pool required for FA anabolism (biosynthesis)

Question 29

different forms of neutral fats (3)

Answer 29

1. monoacylglycerol (MAG) 2. diacylglycerol (DAG) 3. triacylglycerol (TAG)

Question 30

how are fatty acids stored?

Answer 30

FA covalently attached to glycerol and stored as neutral fats

Question 31

how is palmitate attached to glycerol

Answer 31

carboxyl group reactive which is activated by ATP/AMP and becomes acyl-CoA before attached to glycerol

Question 32

glycerol structure for attaching fatty acids

Answer 32

has three hydroxyl groups where activated fatty acids attach

Question 33

how is glycerol synthesised

Answer 33

synthesised from DHAP and glycerol-3-phosphate (G-3-P) (G-3-P comes from dihydroxyacetone phosphate (DHAP) - glycolysis)

Question 34

where does triacylglycerol (TAG) form lipid droplets?

Answer 34

inside ER membrane in between phospholipids

Question 35

reactivity of lipid bodies in fat cells (adipose tissue)

Answer 35

stable

Question 36

purpose of adipose cells in soft tissue other than storage

Answer 36

shock absorbers

Question 37

role of lipid bodies in adipose cells

Answer 37

source of energy for near by tissues and muscle cells

Question 38

fatty acid transport (triacylglycerol (TAG) hydrolysis in adipose tissue) (2)

Answer 38

1. free FAs pass through membranes and enter blood stream 2. free FAs bind to human serum albumin (HSA)

Question 39

FA transport to mitochondria (FA entry into muscle cells)

Answer 39

FAs offloaded from HSA, enter muscle cell and move into outer membrane of mitochondria where they are activated

Question 40

fatty acid transport across inner mitochondrial membrane (3)

Answer 40

1. FAs first react with zwitterionic alcohol (carnitine) 2. acyl-carnitine transported across bilayer by translocase (exchanges carnitine and acyl-carnitine) 3. FAs reattached to CoA once in matrix replacing carnitine with CoA (carnitine transferase II)

Question 41

describe the process of FA transport across the mitochondrial membrane (4)

Answer 41

1. FAs offloaded from HSA, enter muscle cell, pass outer membrane -> inter-membrane space where they are activated by CoA -> acyl-CoA 2. CoA replaced by zwitterionic alcohol (carnitine) by carnitine transferase I -> acyl-carnitine 3. acyl-carnitine translocated -> matrix by acyl-carnitine translocase 4. carnitine in acyl-carnitine replaced by CoA by carnitine transferase II within matrix, -> acyl-CoA

Question 42

fates of neutral fats (4)

Answer 42

1. FA ingested in forms of neutral fat and absorbed by muscle cells to be used as duel (B-oxidation) 2. glycerol recycled in liver 3. excess neutral fats may be absorbed and stored by liver and/or adipose tissue 4. excess acetyl-CoA (by B-oxidation) converted to ketone bodies to be used in heart and renal cortex

Question 43

how do normal tissues obtain fatty acids?

Answer 43

diet

Question 44

how do tumour tissues obtain fatty acids?

Answer 44

de novo fatty acid synthesis by human fatty acid synthase (hFAS) (hFAS activity hallmark of cancer progression)

Question 45

how many carbons does acyl-CoA have

Answer 45

8

Question 46

how many carbons does acetyl-CoA have

Answer 46

2