Set 4 Fa Synthesis

Front 1

Where does FA syth occur?n

Back 1

In the cytosol

Front 2

What is the electron donor for FA synth?

Back 2

NADPH

Front 3

What are the 4 steps of FA synth?

Back 3

CRDR (CONDENSATION, Reduction, Dehydration, Reduction) - Carly Rae Doesn't rock

Front 4

When does Fatty Acid synthesis occur?

Back 4

During times of plenty, when Insulin is produced instead of glucagon.

Front 5

FAs getting degraded are in the __ configuration

Back 5

L

Front 6

FAs getting synthesized are in the __ configuration

Back 6

D

Front 7

Where is Acetyl-Coa primarily located in cells

Back 7

In the mitochondrial Matrix. It needs to be transported into the Cytosol for FA synth.

Makes sense, as FAs undergo B-OX in the mitochon matrix. And Pyruvate gets converted to Acetyl CoA by Pyruvate Dehydrogenase (PDH) in the mitochondrial matrix.

Front 8

How does Acetyl CoA get from the MT matrix to the cytosol?

Back 8

Through the Citrate shuttle

Acetyl CoA (2C) condenses with OAA (4C) to form Citrate (6C), and Citrate is transported through the Citrate transporter on the inner MT membrane

Front 9

When Citrate gets into the Cytoplasm from the MT matrix, it is cleaved by ______ into ______ and ______ . This requires _____

Back 9

Cleaved by Citrate lyase

into OAA and Acetyl CoA

The Splitting of 1 ATP

Front 10

Why Does Citrate move across the MT membrane into the Cytosol?

Back 10

So it can be broken down into Acetyl CoA, and so it can subsequently be used to synth FAs.

Citrate Lyase is positively regulated by insulin, and isocitrate dehydrogenase (TCA cycle enzyme in the MT matrix) is negative regulated by increased [NADH] and [ATP]

Front 11

How does OAA get into the MT matrix?

Back 11

It cannot get into the matrix as OAA. To get OAA back into the matrix after is formed from the splitting of citrate, it must be converted to Malate by cytosolic Malate Dehydrogenase. Malate can re enter the MT. Malate Dehydrogenase requires NADH + H+, or it produces these two products, depending on which way it goes. (production of OAA from malate produces NADH + H+)

Front 12

What is an isoenzyme?

Back 12

2 enzymes that catalyze the same chemical reaction, but have slightly different AA sequence.

Front 13

What enzyme converts Malate into Pyruvate?

Back 13

Malic Enzyme

Front 14

How does pyruvate get converted into OAA?

Back 14

It gets carboxylated by pyruvate carboxylase to form OAA

Front 15

WHat are the 2 ways that NADPH gets made in the cell?

Back 15

NADPH is produced when Malate is converted into Pyruvate + CO2, by Malic enzyme.

2 NADPH get made during the pentose Phosphate pathway, in which
glucose-6-Phosphate gets converted into ribulose 5 phosphate

Front 16

How does Malonyl CoA get produced from Acetyl CoA

Back 16

Acetyl CoA + HCO3- + ATP --> Malonyl CoA + H+ + ADP + Pi. Catalyzed by Acetyl CoA Carboxylase. (ACC). Committed step in FA synth, requires Energy and is Irreversible.

Front 17

What is the "Committed step" in Fatty Acid Synthesis?

Back 17

the formation of Malonyl CoA from Acetyl CoA using the Catalyst Acetyl Acl Carboxylase (ACC). Requires an input of ATP. This step is irreversible

Front 18

What is the structure of Fatty Acid Synthase I (FAS I)

Back 18

It is a homodimer, composed of two identical polypeptide chains.

Front 19

How many Domains are there on FAS I

Back 19

7

Front 20

What are the two domains on FAS I we need to know, and what functional groups do they have that make them important?

Back 20

The KS (B-Ketoacyl ACP Synthase) domain and the ACP (Acyl Carrier protein) domain. They both have thiol groups, which can allow them to bind to Malonyl CoA and Acetyl CoA, and when the thiol bonds b/w FAS and Acetyl CoA or Malonyl CoA break, the rxn is highly exergonic.

Front 21

In FA synthesis, how big is the FA that is made (before any elongation steps)

Back 21

C16:0 Palmitate.

Front 22

Where do the Carbons For FA synthesis come from

Back 22

2 come from Acetyl CoA (the 2 Cs at the terminal end), and the rest of the carbons come from Malonyl CoA

Front 23

What is the first preliminary step of FA Synthesis?

Back 23

an acetyl group is added to the thiol group of ACP (acyl Carrier protein), and one CoA is lost. The Acetyl group is then transferred onto the Thiol group of the KS domain.

Front 24

what is the second preliminary step of FA synthesis ?

Back 24

The Malonyl Group of Malonyl CoA is aded onto the thiol group of ACP, and a CoA is lost.

Front 25

Why do Cells add on Co2 onto Acetyl CoA to make Malonyl CoA if it just going to be removed during the Condensation step of FA synthesis.

Back 25

because decarboxylation rxns are very exergonic, so when this condensation reaction occurs, and CO2 is lost, the the rxn is highly energetically favourable.

Front 26

Which Domain on FAS I does the first step (condensation) of FA synthesis occur?

Back 26

ACP

Front 27

Malonyl groups are added onto FAS I on which domain?

Back 27

The ACP Domain.

Front 28

What is the balanced equation for the first round of FA synthesis ?

Back 28

Acetyl-CoA + Malonyl CoA + 2NADPH + 2H+ ---> C4:0-ACP + CO2 + 2CoA + 2NADP+

Front 29

How many H20 Are made during the production of palmitate (C16:0)

Back 29

6 H20s (7 rounds) However, 1 H20 is used to hydrolyze the FA

Front 30

What fatty Acid product is made from FAS I after FA synthesis? And how many rounds of CRDR does this take?

Back 30

Palmitate (C16:0) 7 rounds.

Front 31

Where does Fatty Acid elongation occur?

Back 31

On the Cytosolic face of the Smooth ER.

Front 32

What is the only difference between Fatty Acid Synth, and Fatty acid elongation?

Back 32

The enzyme used. FAS I adds a total of 16 Carbons together. Other enzymes add 2 carbons on at a time by adding Malonyl groups on, coupled to a decarboxylation of the carboxyl group on malonyl (similar to how regular FA synth occurs)

Front 33

Which enzyme adds double bonds to FAs? And what type of double bonds do they add?

Back 33

FA desaturase. Cis double bonds

Front 34

Which double bonds can humans add into their fatty Acids, and what number carbon can the double bonds not go past?

Back 34

4,5,6 and 9. Cannot add double bonds past Carbon 9. Humans must ingest FAs that have double bonds past Carbon 9.

Front 35

ACC is activated during __________. When ACC is activated it is:

Back 35

Times of plenty. Dephosphorylated.

Front 36

Does FA synth and B Ox happen at the same time?

Back 36

No, this would cause a futile cycle.

Front 37

Which hormones inhibit FA synthesis (inhibit ACC)

Back 37

Glucagon and epinephrine.

Front 38

Which molecule diverts the consumption of fuel in the cell from to Storage of FAs?

Back 38

Citrate

Front 39

When is Citrate Moved from the matrix of the MT into the cytosol?

Back 39

When [acetyl CoA] and [ATP] is high

Front 40

How does Citrate prevent Carbon flow through glycolysis?

Back 40

Citrate inhibits Function of Phosphofructokinase 1, preventing the further oxidation of glucose.

Front 41

What Fatty Acid synthesis End product can inactivate ACC?

Back 41

Palmitoyl-CoA (C16:0) can inactivate ACC>

Front 42

Which enzyme adds a CoA to a Fatty Acid chain?

Back 42

Acyl CoA Synthase.

Front 43

When Blood-glucose levels are high, ______ is secreted from the pancrease

Back 43

Insulin.

Front 44

What is the the molecular role of insulin, and what Enzyme does it bind to, to carry out it's role.

Back 44

Insulin binds to insulin dependant phosphatase to dephosphorylate ACC, activating it. When ACC is dephosphorylated, it can catalyze the production of Malonyl CoA, which is the committed step in FA synthesis.

Front 45

Which Molecule Inhibits Carnitine Transferase I (CAT I), and why is this important?

Back 45

Malonyl CoA inhibits CAT I. This is important, as CAT I is used to transport FAs into the MT matrix for B-OX. By inactivating CAT I with Malonyl CoA, the cell can ensure that whenever it is committed to FA synthesis, it will not carry out B-OX. If B-OX and FA synth occurred at the same time, it would be a futile cycle.

Front 46

When blood glucose levels are low, which molecule is secretes by the pancreas?

Back 46

Glucagon

Front 47

With respect to FA synthesis, what is the role of glucagon in the cell?

Back 47

increased glucagon levels activates PKA (protein Kinase A), which can phosphorylate ACC, inactivating it (preventing FA synthesis)

Front 48

With respect to FA mobilization, what is the role of glucagon in the cell?

Back 48

Glucagon binds to a sensor protein on the cell surface of adipocytes, which will activate G protein, which activates Adenyl Cyclase, forming cAMP. cAMP phosphorylates PKA, and PKA phosphorylates HSL (hormone sensitive lipase) and Perilipins. Phosphorylating perilipins allows TAGs to leave the lipid droplet within the cell. HSL cleaves the FAs off of the TAG, and FAs are shipped into the blood stream, and they move through the blood bound to serum albumin.

Front 49

Which enzyme cleaves cAMP --> AMP in adipocytes?

Back 49

cAMP Phosphodiesterase (cAMP PDE)

Front 50

WRT FA synthesis, which enzyme acts a fuel gauge in the cell, and how does it work?

Back 50

AMP dependant Protein Kinase. (AMPK) is activated by a high AMP/ATP ratio, and it phosphorylates ACC, inactivating it. This makes sense, as if [AMP] concentration is high relative it [ATP], the cell needs to produce E, via Beta Ox (and therefore, the cell would want to prevent FA synth)

Front 51

Which Molecule, other than insulin dependent Phosphatase, can dephosphorylate ACC, and how is it regulated.

Back 51

Phosphatase 2a. Phosphatase 2a is inhibited by glucagon, as phosphatase 2a must be dephosphorylated to be active (and PKA can phosphorylate phosphatase 2a. Phosphatase 2a is inactive when phosphoorylated.

Front 52

Which Enzymes in FAS I are used for each step? (other than ACP and KS)?

Back 52

1st reduction -> KR
Dehydration-->DH

2nd reduction -->ER

Release of FA by adding H20--> TE