lipid metabolism I

Question 1

major source of carbon for fatty acid synthesis is

Answer 1

dietary carbohydrates

Question 2

fatty acid synthesis-overview

occurs primarily in ____

also occurs in ____ tissue, ____ , ____ and ____ ____ ____

requires coordination between ____ and ____ reactions

Answer 2

liver

adipose tissue, brain, kidneys, lactating mammary glands

cytosolic and mitochondrial

Question 3

end product of FA synthesis

Answer 3

palmitic acid (16 carbon molecule)

Question 4

precursor of FA synthesis

Answer 4

acetyl CoA (2 carbon molecule)

Question 5

phase I of FA synthesis

Answer 5

cytosolic entry of Acetyl CoA (made in mitochondrial matrix but needed in cytoplasm)

Question 6

phase II of FA synthesis

Answer 6

generation of Malonyl CoA (acetyl CoA is carboxylated to malonyl CoA. most important substrate in FA synthesis. RATE LIMITING REACTION)

Question 7

phase III of FA synthesis

Answer 7

fatty acid chain formation (the enzyme Fatty Acid Synthase catalyzes 7 rxns that incorporate Acetyl CoA and Malonyl CoA into Palmitate, a C16 FA)

Question 8

phase I - cytosolic entry of Acetyl CoA:

1. condenstation of Acetyl CoA with ____ to form ____ (catalyzed by ____ ____ )
2. transport of citrate from mitochondria to cytosol. via a ____ ____
3. citrate converted back to ____ ____ and ____ (catalyzed by ____ ____ )
4. oxaloacetate (OAA) reduced to ____ (catalyzed by ____ ____ )

regeneration of Oxaloacetate (OAA):

1. malate transported into mitochondria via ____ ____ transporter and oxidized to ____ by ____ ____
2. cytosolic malate converted to ____ by ____ enzyme. Pyruvate transported to mitochondira via pyruvate tranporter and carboxylated to OAA by pyruvate carboxylase

Answer 8

1. oxaloacetate (OAA) citrate citrate synthase
2. citrate transporter
3. Acetyl CoA and OAA citrate lyase
4. malate malate dehydrogenase
5. malate-alpha ketoglutarate OAA malate dehydrogenase
6. pyruvate malic

Question 9

citrate lyase regulation:

activators:

inhibitors:

Answer 9

activators: glucose, insluin
inhibitors: PUFA, leptin

Question 10

phase II Generation of Malonyl CoA:

1. cytosolic Acetyl CoA (2 carbon) is converted to ____ ____ (3 carbon) by carboxylation.
   
   1. catalyzed by ____ ____ ____ (RATE LIMITING ENZYME OF FA BIOSYNTHESIS PATHWAY)
   2. ACC adds a ____ to acetyl CoA
   3. uses ATP (for energy) and ____ as co-factor
   4. ACC exists in dimeric ( ____ ) or polymeric ( ____ ) forms

Answer 10

1. Malonyl CoA
   
   1. Acetyl CoA Carboxylase (ACC)
   2. CO₂
   3. Biotin
   4. inactive active

Question 11

regulation of Acetyl CoA carboxylase (ACC):

activators:

inhibitors:

Answer 11

activators: citrate, insulin
inhibitors: glucagon, epinephrine, high [AMP], palmitate, PUFA

Question 12

malonyl CoA:

substrate for:

regulator - inhibits:

prevents FA synthesis and ____ from occuring simultaeneously

Answer 12

Fatty Acid Synthase (FAS)

carnitine acyltransferase (rate limiting step in FA degration)

degradation

Question 13

phase III: FA chain formation:

1. 2 carbon units from malonyl CoA are sequentially added to the growing fatty acyl chain in ____ rxns to form ____ (16:0)
2. the rxns of FA synthesis occur on the ____ ____ ____ complex

Answer 13

1. 7 rxns palmitate
2. fatty acid synthase (FAS)

Question 14

fatty acid synthase (FAS):

large ____-____ complex

composed of 2 identical ____

2 dimers arranged in ____ to ____ conformation

each monomer has ____ enzyme activites and an ____ ____ ____ (ACP)

Answer 14

multi-enzyme

dimers

head to tail

7 acyl carrier protein (ACP)

Question 15

acyl carrier protein (ACP) has a ____ arm consisting of a ____ group that picks substrates and directs substrates to different enzymes in complex

Answer 15

flexible

phosphopantetheine

Question 16

stoichiometry: palmitate synthesis reaction:

Answer 16

1 acetyl CoA + 7 Malonyl CoA + 14 NADPH + 14 H⁺ → CH₃(CH₂14COO^- (palmitate) + 14 NADP⁺ + 8 CoA + 6 H₂​O

Question 17

reactions catalyzed by FAS

Answer 17

1. first cycle
   
   1. Cys-SH of FAS binds to acetyl group
   2. Pan-SH on FAS binds to malonyl group
2. condensation to form beta-ketoacyl group
3. reduction
4. dehydration
5. reduction
6. Cys-SH on FAS is now free
7. 4-C fatty acyl group on Pan-SH is transferred to Cys-SH on FAS
8. another new malonyl group is attached to Pan-SH and cycle repeats 6x

Question 18

sources of NADPH

Answer 18

malic enzyme: 1 molecule of NADPH

pentose phosphate pathway: 2-12 molecules of NADPH

Question 19

regulation of FA synthesis:

gene expression of the enzymes are induced by

Answer 19

low fat, high carb diet

(ATP citrate lyase) - phase I

(Acetyl CoA Carboxylase (ACC) - phase II - rate limiting step

(Fatty acid synthase) - phase III

Question 20

regulation of ATP citrate lyase:

stimulated by ____

gene expression induced by ____/____

induction of gene expression counteracted by ____ ____ ____

induction of gene expression couteracted by ____

Answer 20

phosphorylation

glucose/insulin

polyunsaturated fatty acids (PUFAs)

leptin (hormone that senses fat content of body)

Question 21

acetyl CoA carboxylase:

____ dimer , ____ polymer

Answer 21

inactive active

Question 22

regulation of acetyl CoA Carboxylase:

1. allosteric regulation
   
   1. activator:
   2. inhibitor:
2. phosphorylation (inhibits) / dephosphorylation (activates)
   
   1. activators:
   2. inhibitors:
      
3. induction
   
   1. gene expression up-regulated by ____ ____ / ____ ____ diet

Answer 22

1. allosteric regulation
   
   1. activator: citrate
   2. inhibitor: long chain fatty acids (palmitate)
2. phosphorylation (inhibits) / dephosphorylation (activates)
   
   1. activators: insulin via activation of protein phosphatase
   2. inhibitors:
      
      1. epinephrine via activation of PKA
      2. glucagon via activation of PKA
      3. AMP via activation of AMP kinase (energy sensory)
3. induction
   
   1. gene expression up-regulated by high carb / low fat diet

Question 23

regulation of Fatty Acid Synthase (FAS):

1. allosteric effect (presence of phosphorylated sugars) - ____ activity
2. induction and repression at gene level
   
   1. insulin and glucocorticoid hormones ____ synthesis
   2. high carb / low fat diet ____ synthesis
   3. high fat diets as well as starvation ____ synthesis
   4. high PUFA ____ synthesis

Answer 23

1. increase
2. 1. increase
   2. increase
   3. lowers
   4. suppresses

Question 24

synthesis of longer chain FA - elongation:

1. elongation: palmitate converted to longer chain FA in ____ ____ ____ or ____
2. brain cells need longer chain fatty acids ( ____ - ____ )
3. FA lengthened 2 carbons at a time by the enzyme ____ ____ ____
4. ____ is used as reducing power
5. SER pathway uses ____ ____ as carbon donor
6. mitochondria uses ____ ____ as carbon donor

Answer 24

1. smooth endoplasmic reticulum (SER) or mitochondria
2. C18 - C24
3. Fatty Acid Elongase
4. NADPH
5. Malonyl CoA
6. Acetyl CoA

Question 25

desaturation (unsaturation) occurs in ____ \_\_\_\_ ____ , uses ____ and oxygen, and is catalyzed by ____ \_\_\_\_ \_\_\_\_

Answer 25

smooth ER NADPH (or NADH) Acyl CoA Desaturases

Question 26

humans have ____ desaturases ( ____ , ____ , ____ , ____ )

Answer 26

4 delta⁴ , ⁵, ⁶, and ⁹ can introduce double bonds between carbons 4-5, 5-6, 6-7, and 9-10

Question 27

FAs with double bonds beyond carbon 9 and 10 cannot

Answer 27

be synthesized in humans e.g. omega 3 and omega 6 FA (need to ingest them or their precursors in diet)

Question 28

precursors of FA with double bonds beyond carbons 9 and 10 are called

Answer 28

essential fatty acids

Question 29

_essential fatty acids:_ need to ingest these via diet or their precursors:

Answer 29

linoleic acid (18:2 w6) and linolenic acid (18:3 w3)

Question 30

linoleic acid used to make ____ acid (20:4 w6) a precursor for jeicosanoids (prostaglandins, leukotriences, and thromboxanes) linolenic acid used to make ____ acid (EPA) (20:5 w3) and ____ acid (DHA) (22:6 w3)

Answer 30

arachidonic eicosapentanoic docosahexanoic \*DHA is important for brain fxn; present in breast milk

Question 31

benefits of w3 and w6 FAs

Answer 31

immune system cardiovascular system nervous system vision cell membrane

Question 32

FAs are incorporated into

Answer 32

triacylglycerols (the storage form of lipids - used for energy)

Question 33

pound for pound, TAGs contain about ____ times as much energy as \_\_\_\_

Answer 33

6.75 carbs

Question 34

_typical 70kg man fuel stores:_ 40 kCal ____ (blood) 600 kCal in ____ (liver and muscle) 24,000 kCal in ____ (muscle) 100,000 kCal in ____ (in fat and muscle)

Answer 34

glucose glycogen protein TAGs

Question 35

_TAGs_ backbone: -OH are replaced with:

Answer 35

glycerol fatty acids

Question 36

_building TAGs occurs in 3 locations:_ dietary TAG (processed in ____ cells) De Novo TAG (in ____ ) De Novo TAG (in ____ )

Answer 36

intestinal hepatocytes adipocytes

Question 37

_TAG synthesis in Liver:_ glucose: 1. glucose → ____ (via glycerol 3-phosphate dehydrogenase) glycerol: 1. glycerol → ____ (via glycerol kinase) acetyl CoA: 1. acetyl CoA → ____ \_\_\_\_ → ____ \_\_\_\_ ____ (via fatty acyl CoA Synthase) overall: 1. glycerol 3-P + fatty acyl CoA → ____ acid → ____ acid → diacylglycerol (DAG) → Triacylglycerol TAG → \_\_\_\_

Answer 37

glucose: 1. glucose → glycerol 3-P (via glycerol 3-phosphate dehydrogenase) glycerol: 1. glycerol → glycerol 3-P (via glycerol kinase) acetyl CoA: 1. acetyl CoA → fatty acid → fatty acyl CoA (via fatty acyl CoA Synthase) overall: 1. glycerol 3-P + fatty acyl CoA → lysophosphatidic acid → phosphatidic acid → diacylglycerol (DAG) → Triacylglycerol TAG → VLDL

Question 38

steps in TAG synthesis in liver

Answer 38

glycerol 3-P → lysophosphatidic acid → phosphatidic acid → diacyl glycerol → triacyl glycerol

Question 39

_TAG synthesis in liver key points:_ 1. glucose and glycerol form ____ using different pathways 2. Glucose 3-P used as ____ for TAG synthesis 3. Free fatty acids (FFA) (synthesized in liver from ____ \_\_\_\_ ) added to glycerol 3-P to form TAGs 4. TAGs packaged with apolipoproteins and other lipids (phospholipids) to form a lipoprotein called \_\_\_\_ 5. VLDL released into \_\_\_\_ 6. TAG synthesis in hepatocytes promoted by excess \_\_\_\_

Answer 39

1. glycerol 3-P 2. backbone 3. acetyl CoA 4. VLDL (very low density lipoproteins) 5. bloodstream 6. carbohydrates

Question 40

_TAG synthesis in adipocytes key points:_ 1. glucose forms \_\_\_\_ 2. glycerol 3-P used as ____ for TAG synthesis 3. Free fatty acids (FFA) (obtained from breakdown of ____ and ____ in blood) by the action of ____ \_\_\_\_ \_\_\_\_ 4. glycerol 3-P and free fatty acids form \_\_\_\_ 5. TAGs stored in \_\_\_\_ 6. TAG synthesis in adipocytes promoted by excess ____ and \_\_\_\_

Answer 40

1. glycerol 3-P 2. backbone 3. chylomicrons and VLDL capillary lipoprotein lipase 4. TAGs 5. adipocytes 6. carbohydrates and fats