Biochem 3-05

Front 1

How long do glycogen stores last in the body?

Back 1

About a day.

Front 2

What fat has 16 carbons and no double bonds? (C16:0)

Back 2

Palmitate. We produce this.

Front 3

What fat has 18 carbons and no double bonds? (C18:0)

Back 3

Stearate

Front 4

What fat has 18 carbons and 1 double bond? (C18:1)

Back 4

Oleate

Front 5

What fat has 18 carbons and 2 double bonds? (C18:2)

Back 5

Linoleate

Front 6

How do fatty acids travel around in the body?

Back 6

Carried by albumin in the blood because FA not water soluble.

Front 7

What happens if there are free FA in the body?

Back 7

Acts like a soap and breaks down lipid bylayers.

Front 8

How long are very long chain fatty acids (VLCFA)?

Back 8

>20 carbons

Front 9

How long are short chain FA (SCFA)?

Back 9

<6 carbons

Front 10

What is the term for FA 12-20 carbons long?

Back 10

Long chain FA (LCFA)

Front 11

What is the term for FA 6-12 carbons long?

Back 11

Medium chain FA (MCFA)

Front 12

How do you make a fatty acyl CoA from a FA?

Back 12

Fatty acid synthetase helps put together FA and AMP (from ATP, hydrolysis releases energy to drive reaction forward). Then CoASH comes in and attacks the carboxyl carbon. This lets AMP go away and voila, you have a fatty acyl CoA!

Front 13

What are the three fates of fatty acyl CoA?

Back 13

-Produce energy via beta-oxidation
-Synthesize membranes
-Stores as tryacylglycerols

Front 14

What is the next step for the fatty acyl CoA, after it's formed in the cytosol?

Back 14

Fatty acyl CoA cannot go into the mitochondria as is. Instead, it drops the CoA and puts on carnitine to become fatty acyl carnitine, which can cross the inner mito membrane. Once on the other side, fatty acyl carnitine puts off carnitine and puts CoA back on to reform as fatty acyl CoA.

Front 15

What is the net from the carnitine transport system? What kind of transport is the carnitine transport system?

Back 15

-FA~CoA (intermembrane space) --> FA~CoA (mito matrix). Now it's ready for beta-oxidation!
-Antiporter

Front 16

What are the three enzymes involved in the carnitine transport system for fatty acyl CoA?

Back 16

-Carnitine palmitoyl transferase I (CPT I)
-Carnitine acylcarnitine translocase
-Carnitine palmitoyl transferase II (CPT II)

Front 17

What are the steps in fatty acid catabolism?

Back 17

-Activation to fatty acyl-CoA
-Transport into the mitochondiria via fatty acyl carnitine
-beta-Oxidation

Front 18

Describe how fatty acids are activated to fatty acyl-CoA.

Back 18

-The fatty acyl attacks ATP, forming fatty acyl AMP and pyrophosphate (hydrolyzed to 2Pi.)
-CoASH attacks the carbonyl carbon of fatty acyl AMP.
-AMP is released and fatty acyl CoA is created.
--Two high energy phosphate bonds are hydrolyzed during creating of fatty acyl-CoA.

Front 19

Describe how fatty acyl-CoA (created in the cytosol) gets into the inner mito membrane.

Back 19

-Fatty acyl-CoA easily crosses the outer mito membrane.
-Carnatine palmitoyl-transferase I (outer mito membrane-bound enzyme) converts FA-CoA into fatty acylcarnitine.
-The carnitine acylcarnitine translocase is an inner mito membrane-bound enzyme that transports fatty acylcarnitine into the inner mito matrix (antiporter- fatty acylcarnitine goes in, carnitine goes out).
-Fatty acylcarnitine is acted upon by carnitine palmitoyl-transferase II (inner mito membrane-bound enzyme) and coverts it to fatty acyl-CoA.

Front 20

What type of transporter is carnitine acylcarnitine?

Back 20

Antiporter- fatty acylcarnitine goes in, carnitine goes out

Front 21

What is the name of the outer mito membrane-bound enzyme involved in fatty acid catabolism?

Back 21

Carnitine palmitoyl transferase I- converts FA-CoA into fatty acylcarnitine.

Front 22

Describe beta-oxidation. Start with fatty acyl CoA in inner mito matrix.

Back 22

Fatty acyl CoA in inner mito matrix.
-Double bond formed between C2 and C3 (beta carbon) by acyl CoA dehydrogenase. (Releases FAD2H)
-Hydroxyl group added to C3 (beta carbon) by enoyl CoA hydratase.
-Hydroxyl group on C3 (beta carbon) converted to carbonyl group by b-hydroxy acyl CoA dehydrogenase. (Releases NADH)
-CoASH attacks C3 (beta carbon with carbonyl group), cleaving bond and releasing Acetyl CoA (enzyme: b-keto thiolase) and forming fatty acyl CoA with 2 fewer carbons!
-Net = 1FAD2H and 1NADH and 1AcCoA (to enter TCA cycle or become a ketone).

Front 23

If you start with Palmitoyl-CoA (16C saturated fatty acid), what is your net yield before the TCA cycle?

Back 23

7NADH (17.5 ATP in ETC)
7FAD2H (10.5 ATP in ETC)
8AcCoA (80 ATP in TCA cycle and ETC)
Total=108 ATP!

Front 24

If you start with an unsaturated FA, what are three problems that you can run into?

Back 24

-C=C may not be between C2 and C3
-May create cis double bonds instead of trans (trans is recognized by CoA hydratase)
-May have a conjugated double bonds (not recognized by enzymes)

Front 25

What is the enzyme required if an unsaturated FA ends up with a C=C between C3 and C4?

Back 25

Enoyl CoA isomerase will move C=C to C2 and C3.

Front 26

What is the enzyme required if an unsaturated FA ends up with a conjugated double bond? C=C-C=C

Back 26

2,4 dienoyl reductase (requires oxidation of NADPH)

Front 27

Why is energy production from an unsaturated FA less than from a saturated FA?

Back 27

-Less FAD2H is produced (because in the first step of beta-oxidation, you form a a C=C between C2 and C3 and produce FAD2H)
-You expend NADPH to oxidize conjugated double bonds.

Front 28

What is produced when you have an odd chain length FA? Where can you also find this other unique product?

Back 28

Produce AcCoA until you get down to 3 carbons and then you release Propionyl CoA. You will also find Propiony CoA from metabolism of branched chain amino acids (leucine, isoleucine, valine)

Front 29

What happens with propionyl CoA (produced from odd chain fatty acids and catabolism of branched chain amino acids-valine, leucine, isoleucine)?
What is the role of Vit B12 (cobalamin) in this reaction?

Back 29

-Propionyl CoA is converted to succcinyl CoA, which is an intermediate in the TCA cycle (anapleurotic reaction).
-Vit B12 (cobalamin) serves as a conenzyme in the final step, where L-methylmalonyl CoA is converted to Succinyl CoA by methylmalonyl CoA mutase.

Front 30

How do medium chain fatty acids get into the inner mito matrix for b-oxidation? What enzyme converts them to FA-CoA?

Back 30

Do NOT require the carnitine transport system. Use a monocarboxylate transporter to go directly into the inner mito membrane where they are converted to fatty-acyl by MCL-AcCoA Synthetase (requires ATP).

Front 31

What are the 4 enzymes required for a saturated LCFA?

Back 31

-Acyl CoA dehydrogenase (to create a C=C between C3 and C4)
-Enoyl CoA hydratase (to add a hydroxyl group onto C3)
-b-hydroxy acyl CoA dehydrogenase (to convert the carboxyl group on C3 to a carbonyl group)
-b-keto thiolase (to cleave 2 carbons off as AcCoA)

Front 32

What two additional enzymes are required for unsaturated FA?

Back 32

-Enoyl CoA isomerase
-2,4 dienoyl reductase

Front 33

What 3 enzymes (and 1 coenzyme) are required for synthesis of Propionyl CoA? What is the fate of propionyl CoA?

Back 33

-Propionyl CoA carboxylase
-Methylmalonyl CoA epimerase
-Methylmalonyl CoA mutase (requires Vit B12 as cofactor).
**Propionyl CoA eventually is processed to become succinyl CoA, and feeds into the TCA cycle.

Front 34

How is the FA catabolism pathway regulated to prevent a futile cycle with FA biosynthesis? (2 ways)

Back 34

#1-The product of the committed step of FA biosynthesis is Malonyl CoA.
-Malonyl CoA shuts down carnitine palmitoyl transferase, which is the enzyme that converts FACoA into FA-carnitine for transport into inner mito membrane. This is known as compartmentalization (keeps FACoA out of the inner mito membrane where it's broken down).
-Ratio of NAD+/NADH

Front 35

What happens to VLCFA?

Back 35

-Go to peroxisome
-Trimmed down to:
-Acetyl CoA
-MCFA CoA
-SCFA CoA
-Also releases H2O2 and produces NADH
-AcCoA, MCFA CoA, and SCFA CoA are converted to Acetyl-carnitine, MCFA-carnitine, and SCFA-carnitine for transport out of the peroxisome and into the inner mito membrane.

Front 36

What is the biggest difference between the first step of the peroxisomal pathway and the first step of the regular b-oxidation pathway?

Back 36

The first step in the peroxisomal pathway does NOT produce energy as FAD2H (FAD2H goes to create H2O2 instead).

Front 37

What happens in Zellweger syndrome?

Back 37

There are NO peroxisomes, therefore, VLCFAs accumulate in tissues, particularly liver and brain.

Front 38

a-oxidation of VLCFA can occur in brain and other nervous tissue. Describe this process.

Back 38

-C1 is the carbonyl carbon (same as regular b-oxidation)
-Through multiple oxygen insertions (by a-hydroxylase) on the a-carbon, decarboxylations and/or chain cleavage is possible.

Front 39

What is the problem with branched LCFAs undergoing b-oxidation? What is the solution?

Back 39

-Branched LCFAs can have a methyl group on the b-carbon, which creates problems during the third step of b-oxidation when OH is oxidized.
-Solution:
-a-oxidation to remove C1
-a-hydroxylase to insert oxygen and make C2 a COOH (becomes the new C1)

Front 40

What is a-hydroxylase deficiency called?

Back 40

Refsum dx

Front 41

What is the importance of omega-oxidation? Where does it occur?

Back 41

-Able to remove 1 carbon at a time if regular oxidation is broken.
-Allows hydrophobic xenobiotics to be excreted
-Occurs in the smooth ER

Front 42

How are ketone bodies produced?

Back 42

-2 AcCoA
-Blah, blah
-Acetoacetate
-Acetoacetate is unstable and becomes 1) acetone and CO2 or is catalyzed to 2) 3-hydroxybutyrate (ketone body) by D-b-hydroxybutyrate dehydrogenase (requires NADH).

Front 43

How are ketone bodies utilized by peripheral tissues?

Back 43

-3-hydroxybutyrate is converted back to acetoacetate by D-b-hydroxyacetate dehydrogenase (produces NADH).
-Acetoacetate is converted to acetoacyl CoA by succinyl CoA:acetoacetate CoA transferase (ENZYME NOT IN THE LIVER!)
-Acetoacyl CoA has another CoA added by thiolase to create 2 AcCoA.

Front 44

What is the key enzyme that is NOT found in the liver that allows peripheral tissues to utilize ketone bodies?

Back 44

Succinyl CoA:acetoacetate CoA transferase.
This enzyme transfer CoA from Succinyl CoA onto acetoacetate, creating succinate and acetoacetyl CoA. Acetoacetyl CoA goes on to be combined with another CoASH (catalyzed by thiolase) to become 2 Acetyl CoA that can enter the TCA cycle.

Front 45

What is the approximate yield from ketone bodies? Compared to glucose?

Back 45

Ketone bodies about 21.5 ATP
Glucose about 30-32 ATP

Front 46

What are 3 physiological conditions in which FA's are used?

Back 46

-Starvation/fasting
-Endurance exercise
-Hight fat/low carb diet

Front 47

What are 3 hormonal conditions which stimulate FA levels to increase?

Back 47

-Increase Glucagon
-Increase Epinephrine
-Decrease insulin

Front 48

What is the key product from FA synthesis that shuts down the carnitine transport system for FA catabolism and prevents a futile cycle?

Back 48

Malonyl CoA

Front 49

Name 6 tissues that can use KB's?
Name 2 tissues that cannot?

Back 49

CAN
-Brain
-Adipose
-Muscle
-Heart
-Intestines
-Fetal
CANNOT
-Liver
-RBC's

Front 50

How is ketone body synthesis regulated?

Back 50

When NADH is not being used, it backs up the TCA cycle and AcCoA is shunted to produce acetoacetyl CoA and then KB.

Front 51

What is the importance of using KB's as fuel in extended starvation?

Back 51

Protein sparing!!