Beta oxidation - Brar

Question 1

how are dietary triglycerides metabolized?

Answer 1

Dietary triglycerides are metabolized by bile acids
Red meat = more fat = more bile acid
Net result is likely tumor promotion manifesting as colon cancer

Bile acids emulsify dietary TG and then pancreatic lipase works on what is left of TG

Question 2

What is the carnitine shuttle and how does it work?

Answer 2

In order to transport fatty acyl CoA’s into mitochondrial matrix for beta oxidation carnitine is used

Acyl CoA synthetase (in the outer mitochondrial membrane) uses ATP to convert free FA in the cytosol into fatty acyl CoA.

Fatty acyl CoA crosses outer mitochondrial membrane into the inter membrane space where it is combined with carnitine by carnitine palmitoyl-transferaseI (CPT I) (also, in the outer mitochondrial matrix) to create fatty acylcarnitine

this fatty acylcarnitine is transported into the matrix via carnitine acylcarnitine translocase

in the matrix, CoA and the fatty acyl carnitine will react via carnitine palmitoyl-transferase II (CPT II) to create a fatty acyl CoA (which will be available for beta oxidation) and a carnitine

carnitine is moved back into the inter membrane space via the same translocase

Question 3

what are the 4 reactions of beta oxidation and what do they produce?

Answer 3

Essentially four reactions which are repeated until an even FA chain is converted to acetyl CoA

1. Dehydrogenation ( generating FADH2 ) via Acyl CoA dehydrogenase--> enoyl CoA
2. Hydration via enoyl CoA hydratase-->3-hydroxyacyl CoA
3. Oxidation ( generating NADH ) via 3 hydroxyacyl CoA dehydrogenase--> 3 ketoacyl CoA
4. Thiolysis via beta-ketoacyl-CoA thiolase and the addition of CoA --> fatty acyl CoA and acetyl CoA 

These four reactions are then repeated
each turn of the four steps produces:
FADH2 = 2 ATP (in electron transport chain)
NADH = 3 ATP
Each turn of cycle yields 17 ATP’s (5 from NADH and FADH2 and 12 from the acetyl CoA) and 2 C’s are cleaved from the fat

Question 4

How many ATP’s are generated for every acetyl CoA made in beta-oxidation?

Answer 4

5

Question 5

How many ATP’S per acetyl CoA through the TCA cycle?

Answer 5

12

Question 6

energy yield of fatty acids?

Answer 6

16 C palmitic acid yields 129 ATP
each cycle adds 17 ATP, for 2 C

so for an 18 C FA, you would get 129+17 ATP=146

Question 7

What additional enzymes are needed for unsaturated fatty acids and polyunsaturated fatty acids ?

Answer 7

Enoyl CoA isomerase to convert cis FA –> trans FA –> the only enzyme needed for monounsaturated FA

2,4-dienyl CoA reductase for PUFA’s to breakdown the conjugated double bonds (in addition to enoyl COA isomerase)

Question 8

How are odd chain FA oxidized? what enzymes are necessary and what are the products?

Answer 8

beta oxidation will take place until a 3 C FA remains (propionyl CoA)

propionyl–> D-methylmalonyl CoA (BIOTIN=required cofactor!!)
–> L-methylmalonyl CoA–> succinyl CoA (coenzyme form of vitamin B12=required!)

succinyl CoA can form malate and enter gluconeogenesis and is also an intermediate of the TCA cycle

Question 9

ketogenesis

Answer 9

acetyl CoA generated by beta oxidation is converted by the liver into ketone bodies (acetone, 3-hydroxybutyrate, and acetoacetate)

ketone bodies are oxidized for energy by the brain, skeletal muscle, kidney and intestinal mucosa ==> during fasting

the NAD+/NADH ratio during FA oxidation determines how much 3-hydroxybutyrate is formed.

acetoacetate is either reduced to beta-hydroxybutyrate or decarboxylated to acetone

Question 10

What are the ketogenic AA?

Answer 10

Certain amino acids are broken down into acetyl CoA or acetoacetyl CoA:

Leucine
Isoleucine
Lysine 
Tryptophan
Phenylalanine
Tyrosine