Question

Explain every step involved in the breakdown of fatty acids. Explain how each enzyme is working and all the chemical structures involved. Also explain how fatty acid breakdown is being regulated to allow a switch between carbohydrate breakdown. Describe how each protein is working in this regulation.

Answer 1

BETA OXIDATION STEPS

After one round of four metabolic steps,one acetyl CoA unit is split off and acyl CoA with 2 Carbon atoms less is generated.This would undergo the same series of reactions again until fatty acids are completely oxidised.

STEP 1: FAD Linked Dehydrogenase

The fatty acyl CoA is dehydrogenated to a transenoyl CoA with FAD accepring hydrogen atoms.FADH₂ when oxidised in electron transport chain will produce 1.5ATP molecules.

STEP 2: Hydartion

This is catalysed by an enoyl CoA hydratase.This step forms a beta-hydroxy fatty acyl CoA.The L isomer alone is formed during the hydartion of the trans double bond.

STEP 3: NAD Dependent Dehydrogenase

The beta-hydroxy fatty acyl CoA is agian oxidised to form beta-keto fatty acyl CoaA.This hydrogenase acts on L isomer.The NADH when oxidised in electron transport chain will generate 2.5 ATP's

STEP 4: Cleavage

The beta-keto fatty acyl CoA now undergoes thiolytic cleavage,splitting of a molecule of acetyl CoA and leaving behind a fatty acid with 2 carbon atoms less.

FURTHER CYCLES

The newly formed fatty acyl CoA will sequentially undergo further cycles of steps 1,2,3 and 4 of beta-oxidation until the fatty acid is completely converted to acetyl CoA

4 Steps of β-oxidation (C16) R-CH2_-CH2-CH2-c- S-CoA Palmitoyl-CoA acyl-CoAFAD 1. Dehydrogenation of the fatty acyl-CoA FADH Step 1 to make a trans double bond between α and β carbon R-CH2 trans-A2 Enoyl-CoA Short, medium, and long chain acyl CoAdehydrogenases e removed transferred to FAD enoyl-CoAH20 hydratase Step 2 2. Hydration of the double bond L-B-Hydroxy acyl-CoA 1. Dehydrogenation of the B-hydroxyl NAD Step 3 group to a ketone - e removed transferred to NAD+ dehydrogenaseNADHH , B-Ketoacyl-CoA 1. Acylation - addition of CoA and production of acetyl-CoA COA-SH Step 4 0 0 (C 14) Acyl-CoA (myristoyl-CoA) Acetyl -CoA

SUMMARY

When one molecule of palmitate undergoes beta-oxidation the net reaction is

$Palmiitoyl CoA +7FAD +7NAD+ +7H2O +7HSCoA \rightarrow 8Acetyl CoA+7FADH2(2 in subscript)+7NADH+7H+(Plus)(+)in super script)$

REGULATION OF BETA OXIDATION

1.The availability of free fatty acids (FFA) regulates the net utilization through beta oxidation.

2.The level of FFA in turn is controlled by glucagon:insulin ratio,Glucagon increases FFA levels and insulin has the opposite effect.

3.CAT-1 is the regulator of entry of fatty acids into mitochondria.Malonyl CoA inhibits CAT-1 activity.Thus during de novo syntesis of fatty acids,beta oxidation is inhibited.