Lecture 8 - Fatty acid oxidation

Question 1

State the length classification for FAs.

Answer 1

• Very long > 20
• Long 12 - 20
• Medium 6 - 12
• Short

Question 2

Explain the general movement of FA oxidation overnight.

Answer 2

1) Adipose cells release long chain FAs
2) Circulate in blood associated with albumin
3) In cells are converted to Fatty acyl-CoA by acyl-CoA synthetase
4) Activated acyl-CoA transported into matrix bound to carnitine
5) Fatty acyl-CoA regenerated in beta ox
6) Oxidizing produces FADH2, NADH, and Acetyl-CoA (all require oxidative phosphorylation to produce ATP)

Question 3

Where are water-soluble, medium chain FAs oxidized?

Answer 3

Do not require carnitine and occurs only in liver

Question 4

What rxn occurs to excess FAs? What are the products and where do the products of this rxn end up?

Answer 4

Gamma-oxidation, dicarboxylic acid products end up in urine

Question 5

Where are very long FA chains processed prior to entering the mitochondria?

Answer 5

Peroxisomes

Question 6

What are acetoacetate and beta-hydroxybutyrate and where are they generated?

Answer 6

Ketone bodies, liver

Question 7

What is the role of Malonyl-CoA?

Answer 7

Inhibits formation of fatty acyl carnitine derivatives

Question 8

Stearic acid

Answer 8

C18 (18 carbons including the carbon of the carboxylic acid)

Question 9

Oleic acid

Answer 9

C18:1 (18 carbons including the carbon of the carboxylic acid + one double bond)

Question 10

Linolenic acid

Answer 10

C18:3

Question 11

Arachidonic acid

Answer 11

C20:4

Question 12

Role of acyl CoA synthetase

Answer 12

Activates FA using ATP. Forms a transient covalent bond with a phosphate in order to allow CoASH to perform nucleophilic attack.

Question 13

Where are the acyl-CoA isozymes required to activate short chain FAs located?

Answer 13

Cytosol or on mitochondrial membrane

Question 14

Where are the acyl-CoA isozymes required to activate medium chain FAs located?

Answer 14

Matrix of mitochondria

Question 15

Where are the acyl-CoA isozymes required to activate long chain FAs located?

Answer 15

Endoplasmic reticulum, outer mitochondrial membrane, or peroxisomal membranes

Question 16

Where are the acyl-CoA isozymes required to activate very long chain FAs located?

Answer 16

In peroxisomes

Question 17

Where is carnitine located? What is its role at this location?

Answer 17

External and internal surfaces of the inner mitochondrial membrane, Shuttles fatty acyl CoA into the matrix.

Question 18

List the enzymes in the beta oxidation spiral in order.

Answer 18

1) Acyl CoA dehydrogenase, enoyl CoA dehydrogenase, beta hydroxy acyl CoA DH, beta-keto thiolase
(ACDH, ECDH, BHACDH, BKT)

Question 19

Palmitic acid

Answer 19

C16

Question 20

List the substrates of the FA oxidation spiral.

Answer 20

1) Fatty acyl CoA
2) Trans ^2 fatty enoyl CoA
3) L-beta-hydroxy acyl CoA
4) Beta-keto acyl CoA

Question 21

What is the role of enoyl CoA isomerase?

Answer 21

Turns a cis unsat bond to a trans (moves it towards the acyl coA end)

Question 22

What is the enzyme that solves the problem of a conjugated trans and cis double bond?

Answer 22

2,4-dienoyl-CoA reductase (step oxidizes NADPH to NADP+ and creates trans fat between sites of original double bonds). NOTE: this creates an beta trans bond which cannot be handled by 3-L-hydoxyacyl DH

Question 23

What enzyme corrects the problem created by 3,2-dienyoyl-CoA isomerase (a beta trans bond)?

Answer 23

3,2-dienoyl-CoA reductase

Question 24

What type of oxidation is required for branched FAs

Answer 24

Alpha oxidation

Question 25

Where does omega oxidation occur?

Answer 25

ER

Question 26

What does omega oxidation of FAs produce?

Answer 26

Dicarboxylic acids (observed in urine if defects in beta ox)

Question 27

What is the effect of low insulin/high glucagon on beta ox?

Answer 27

Activates hormone sensitive lipase > increased FAs

Question 28

Where are ketone bodies synthesized?

Answer 28

Liver mitochondrion

Question 29

What enzyme required for conversion of ketones back to acetyl-CoA is absent in the liver? What does this enzyme do?

Answer 29

Succinyl CoA: acetoacetyl CoA transferase - transfers a CoASH to acetoacetate

Question 30

State the enzymes in order that convert beta-hydroxybutyrate to 2 acetyl-CoA.

Answer 30

1) Beta-hydroxybutrate DH
2) Succinyl CoA:acetoacetyl CoA transferase (thiophorase)
3) Thiolase

Question 31

How many ATP do acetoacetate and beta-hydroxybutyrate produce?

Answer 31

acetoacetate: 19 beta-hydroxybutyrate: 21.5

Question 32

What tissues can only use glucose?

Answer 32

RBC, Renal medulla