Biochem Lecture 25

Front 1

De novo FA synthesis requires Acetyl-CoA but occurs in the __________

Back 1

cytoplasm

Front 2

When energy charge is high (ATP>>ADP), ______________ is inhibited, citric acid builds up and is passively transported to cytoplasm.

Back 2

isocitrate dehydrogenase

Front 3

When energy charge is high (ATP>>ADP), isocitrate dehydrogenase is inhibited, ________ builds up and is passively transported to cytoplasm.

Back 3

citric acid

Front 4

During fatty acid synthesis, what enzyme ensures that mitochondrial oxaloacetate is not depleted?

Back 4

pyruvate carboxylase

Front 5

________ converts citrate to Acetyl CoA & Oxaloacetate in the _________

Back 5

- citrate lyase

- cytoplasm

Front 6

What does citrate lyase do?

Back 6

- converts citrate to acetyl coA & oxaloacetate in the cytoplasm

Front 7

________ generates cytoplasmic acetyl-CoA

Back 7

Citrate lyase

Front 8

______________ makes Malonyl-CoA, a committed building block of FAs

Back 8

Acetyl CoA carboxylase

Front 9

What coenzyme does acetyl CoA carboxylase use?

Back 9

biotin

Front 10

________ is the activated form of acetyl CoA

Back 10

Malonyl CoA

Front 11

How does ping-pong mechanism of acetyl CoA carboxylase work? Which enzyme is it very similar to?

Back 11

- biotin is carboxylated to form CO2-biotin enzyme complex, which transfers CO2 to acetyl CoA to form malonyl CoA (transcarboxylase reaction)

- similar to pyruvate carboxylase

Front 12

__________ is the first committed step in FA synthesis. Thus, __________ is tightly regulated.

Back 12

- Malonyl-CoA

- Acetyl CoA Carboxylase

Front 13

When Acetyl CoA Carboxylase is active it is a ______ because of _________

Back 13

- polymer

- dephosphorylation

Front 14

When Acetyl CoA Carboxylase is inactive it is ________ because of ________

Back 14

- depolymerized

- phosphorylation

Front 15

What stimulates protein phosphatase that turns on/polymerized Acetyl CoA Carboxylase?

Back 15

- citrate

Front 16

What stimulates cyclic AMP dependent protein kinase that turns off/depolymerizes Acetyl CoA Carboxylase?

Back 16

- Palmitoyl CoA, Malonyl CoA

- hormones: glucagon & epinephrine

Front 17

FAS uses ___________, ________ and reduced ______ to form FA chains.

Back 17

- Malonyl-CoA

- Acetyl-CoA

- NADPH

Front 18

When do FAS levels increase ~70x?

Back 18

after a CHO-rich meal after a fast

Front 19

FAS is a ______ head to tail each with ___ enzymatic activities & 2 active _____ for forming thioester bonds

Back 19

- homodimer

- 7

- sulfhydryls

Front 20

The two active sulfhydryls on FAS are _____ & ______

Back 20

- Pant SH = Phosphopantetheine sulfhydryl

- Cys SH = Free sulfhydryl on cysteine

Front 21

Where is the Phosphopantetheine sulfhydryl
group found (which domain)? Where is the free sulfhydrylon cystein found (which domain)?

Back 21

- ACP = acyl carrier protein domain

- COND = condensing domain

Front 22

Growing FA chain is held alternatively by -SH of ________ or by ___________

Back 22

- FAS-Cysteine residue

- FAS-linked phosphopantetheine

Front 23

First & second steps in fatty acid biosynthesis include adding acetyl CoA to the phosphopantetheine on _____, and then to the -SH of a cysteine on the ______. This reaction is catalyzed by ______.

Back 23

- ACP

- condensing enzyme portion of FAS

- Acyl Transferase (acetyl transferase or AT)

Front 24

The third step in FAS, malonyl CoA is transferred to a -SH of the phosphopantetheine group of ______, catalyzed by the enzyme _________

Back 24

- ACP

- Malonyl Transferase (MT)

Front 25

The fourth step of fatty acid synthesis involves the condensation of the acetyl group & the malonyl group, liberating _____ & forming 4 carbon acetoacetyl-ACP. This is done by ________. What is unique about the CO2 produced in this reaction?

Back 25

- CO2

- condensing enzyme

- The CO2 is the same one added by Acetyl CoA Carboxylase earlier

Front 26

In steps 5-7 of fatty acid synthesis the newyl snythesized acetoacetyl-ACP (keto-acid) undergoes what 3 reactions?

Back 26

1) reduction
2) dehydration
3) reduction

-reductions give you fully saturated FA, dehydratases give you double bond

Front 27

Fatty acid synthesis proceeds by _____ carbon units until 16 carbons. _________ cleaves off C16 ______, leaving FAS ready for another cycle.

Back 27

- 2

- Thioesterase

- palmitate

Front 28

The chemistry of FA synthesis is esentially the reverse of FA beta-oxidation, how?

Back 28

- beta oxidation: saturated --> enol --> hydroxyl --> keto

- synthesis: keto --> hydroxyl --> enol --> saturated

Front 29

What are the two sources of NADPH for FA synthesis?

Back 29

1) Pentosephosphate pathway

2) NADPH-linked malate dehydrogenase

Front 30

Oxaloacetate generated by _______ is converted to malate which is converted to ______ by ________, which generates NADPH

Back 30

- citrate lyase

- pyruvate

- NADPH-linked malate dehydrogenase (malic enzyme)

Front 31

Overall Requirements for FA synthesis (16:0 palmitate)
___ Acetyl CoA
___ ATP (to convert 7 Acetyl CoA to 7 Malonyl CoA)
___ NADPH (7 b-keto and 7 enoyl reductions)

Back 31

- 8

- 7

- 14

Front 32

Is carbohydrate conversion to FAs efficient (how efficient)?

Back 32

81%

Front 33

How do elongases, desaturases, oxygenases & hydroxylases modify fatty acids?

Back 33

Elongases: Add 2 carbon units (from Acetyl CoA or Malonyl-CoA) to carboxyl end, followed by reduction & dehydration.

Desaturases: Add cis double bonds, generally spaced by 3 carbons,in mammals never closer than omega-7.

Oxygenases: Oxidize polyunsaturated FAs to create intercellular messengers.

Hydroxylases: Add -OH to alpha carbon (C2) of some FAs used in nervous tissues.

Front 34

Fatty acid elongation is a lot like FAS steps, but it occurs on the ______ in the _______. Different enzymes are used. Where does it add? Does it change the omega number?

Back 34

- smooth ER

- mito matrix

- carboxyl end

- DOES NOT CHANGE THE OMEGA NUMBER b/c adding to the carboxyl end

Front 35

What does the desaturase mechanism do? Does it change the omega number? What are it's limits?

Back 35

- desaturase adds cis double bonds

- can change omega number

- CAN ONLY DESATURATE AT OMEGA-7 OR GREATER

Front 36

The essenatial fatty acids are ______ & ________. Where do we obtain these? They are important in membranes & for intercellular signaling.

Back 36

- alpha linolenic acid = omega-3

- linolenic acid = omega-6

- diet

Front 37

Can fats be converted to glucose?

Back 37

NO! THERE IS NO MAMMALIAN ENZYME TO CONVERT ACETYL-COA TO PYRUVATE

Front 38

In the liver & adipose tissue, _______ & _______ are the precursors for TAG syntehsis

Back 38

- glycerol-3-phosphate

- fatty acyl CoA

Front 39

Glycerol-3-phosphate is formed by the reduction of ______ produced during glycolysis. _______ is the enyzme that does this.

Back 39

- DHAP

- glycerol phosphate dehdrogenase

Front 40

Glycerol-3-phoasphate is also formed from glycerol by _______. This enzyme is virutally absent in adipose tissue.

Back 40

glycerol kinase

Front 41

______, released by adipose tissue, suppresses food intake by altering the hormones released from the hypothalamus.

Back 41

Leptin