Cellular Fatty Acid Factories

Front 1

How are Non-Esterified FAs Stored?

Back 1

As tri-acylglyerols (TAGs)

Front 2

What role do Non-esterified Fatty acids serve in the body?

Back 2

Used as fuel molecules

Front 3

Describe the structure of Non Esterified Fatty Acids

Back 3

Long CH chains with a terminal carboxylate group

Front 4

Describe Tri-Acyl Glycerols.

Back 4

1. Uncharged esters of FAs + glycerol

2. Fuel storage molecules

3. Stored in adipocytes

Front 5

What features of TAGs make them good energy stores?

Back 5

1. Being reduced and anhydrous allows them to be highly concentrated stores of energy chemically - 9Kcal / g of TAG.

2. Being non polar allows TAGs to be stored in the anhydrous form allowing a physically tight packing of TAGs in a given space.

Front 6

How much energy does a gram of TAGs yield when catabolised?

Back 6

9 Kcal

Front 7

How much energy does the average 70kg man have stored as TAGs?

Back 7

100,000 Kcal!

(accounts for only 11kg of the overall weight)

Front 8

1. How are dietary lipids absorbed?

2. What is the basic process of this?

Back 8

1. Dietary lipids are digested by pancreatic lipases, they must be degraded before they can be absorbed across the intestinal epithelium.

2. TAGS degraded by lipases to become Fatty acids (FAs) and monoacylglycerides in the gut lumen.

These enter the mucosal cell and recombine into TAGs. Recombined TAGs are formed into chylomicrons which subsequently enter the lymphatic system.

Front 9

What is the chemical mechanism process of TAG degradation? (i.e its conversion into monoacylglycerols (MAG))

Back 9

Process of 2x hydrolytic reactions catalysed by lipases. Results in the formation of 2 FAs and 1 MAG.

Front 10

What the 4 overall steps of Fatty Acid degradation?

Back 10

1. Oxidation

2. Hydration

3. Oxidation

4. Cleavage

Front 11

What is the preliminary step before fatty acid (FA) degradation can begin?

Back 11

Carboxyl group (of the FA) is bound to a -s-CoA group

Front 12

What is the specific name of the process which breaks down fatty acids in mitochondria?

Back 12

Mitochondrial Beta-oxidation

Front 13

How does fatty acid degradation help to fuel respiration?

Back 13

Fatty acids oxidised into Acetyl CoA which can directly enter the Kreb's cycle and thus fuel oxidative phosphorylation

Front 14

What is the distinction between degrading a FA with an even number of carbons and one with an uneven number of carbons?

Back 14

Even number of carbons will completely degrade an even carbon fatty acid with no byproducts, just Acetyl-CoAs

An uneven C number FA will be broken down in the final step into 1x Acetyl CoA and 1x propionyl CoA.

Front 15

What is the specific process by which Acetyl CoA is able to enter the Kreb's Cycle?

Back 15

Acetyl CoA combines with oxaloacetate (formed from carbohydrates) to enter the Kreb's cycle.

Front 16

1. When might Acetyl CoA not be able to enter the Kreb's cycle?

2. What happens instead?

Back 16

1. Lack of carbohydrates (to form oxaloacetate)

2. Diverted to create ketone bodies

Front 17

When is Fatty Acid synthesis necessary?

Back 17

1. During embryonic development

2. Lactation in mammary glands

Front 18

What tissues can synthesise FAs?

Back 18

1. Adipose Tissue

2. Liver

Front 19

What is the basic concept which compares FA synthesis and degradation?

Back 19

The basic mechanism of each is the reverse of the other

ie. Degradation: FAs --> Acetyl CoA ((a) oxidation, (b) Hydration, (c) Oxidation, (d) cleavage)

Synthesis: Acetyl --> CoA ((a) reduction, (b) Dehydration, (c) Reducation, (d) Condensation)

Front 20

What are some key differences between FA synthesis and degradation?

(I.e. Where? Enzymes? Intermediates?)

Back 20

Front 21

What is the basic overall equation for FA synthesis?

Back 21

Acetyl CoA (2C) + Malonyl - CoA ---> Acetoacetyl ACP + ACP + CO2

Front 22

How do enzymes interact with the FA synthesis pathway?

Back 22

Very important multifactorial enzyme called FA Synthase holds malonyl-CoA and anchors the synthesising FA chain in place.

Front 23

1. What is the enzyme which catalyses Fatty Acid Synthesis?

2. What features are key about this enzyme?

Back 23

1. Fatty Acid synthase

2. 7 active sites

Front 24

What are the two functional groups of FA synthase?

Back 24

1. Modification Compartment

2. Selecting and condensing compartment

Front 25

What is the synoptic idea of how FA synthase catalyses FA synthesis?

Back 25

Holds Acetyl-CoA in one area and Malonyl CoA in another.

Catalytic mechanisms to bind one to the other which then rebinds Malonyl CoA to repeat the process to lengthen the FA chain one Malonyl CoA at a time.

Front 26

1. How many carbons is the cut off point for FA synthesis?

2. What is the name of this molecule?

Back 26

1. 16 carbons

2. Palmiate

Front 27

What is the first step of FA synthesis?

Back 27

Step 1 (a) Acetyl group delivered to the 'Ketosynthase' (KS) active site

(b) Malonylacetyl Transferase (MAT) subunit attaches malonyl unit to Acyl Carrier Protein subunit.

(Subunits of FA synthase)

Front 28

What is the second step of FA synthesis?

Back 28

Step 2 (a) Acetyl Carrier Protein (ACP) visits Ketosynthase (KS) subunit again

(b) KS condense acetyl+malonyl units

(c) This forms a Beta-Ketoacyl product, attached to ACP

Front 29

What is the third step of FA synthesis?

Back 29

Step 3 (a) Acetyl Carrier Protein (ACP) delivers the Beta-Ketoacyl product to the KetoReducatase (KR) subunit.

(b) KR reduces the keto group to an alcohol

Front 30

What is the fourth step of FA synthesis?

Back 30

Step 4 (a) DeHydratase (DH) subunit now visits who kindly introduces a double bond

(b) H2O is lost (dehydration)

Front 31

What are Fatty Acids built into?

Back 31

Built into phospholipids and glycolipids

Front 32

What is the fifth step of FA synthesis?

Back 32

Step 5: Now the EnoylReductase (ER) domain wants a piece of the action and reduces the double bond.

Front 33

What is the sixth step of FA synthesis?

Back 33

Step 6: (a) Acetyl carrier protein (ACP) hands the reduced product back to Ketosynthase (KS) - at this point it is clear that the FA chain has basically been extended by one unit.

(b) Malonyl Acetyl Transferase (MAT) now sees Acetyl Carrier Protein (ACP) is now empty and delivers a new malonyl CoA to ACP to begin the cycle anew.

Front 34

How is Fatty Acid Synthase useful for diagnostics?

Back 34

1. Cancer cells upregulate FA synthase expression

2. FA synthase expression = poor prognosis for heart + prostate cancer.

Front 35

How is FA synthesis controlled?

Back 35

Acetyl CoA carboxylase plays an essential role in regulating FA synthesis as it catalyses the production of Malonyl CoA

This is the rate limiting step.