Fatty acid degradation

• fuel, primary source of energy, during rest and moderate activity

• Build phospholipids and glycoprotein

• Bind to proteins for transport and recognition

• Derivatives form hormones and messengers

The main roles of FA’s

White adipose tissue within the cytoplasm of adipocytes located:

• viscerally

• Subcutaneously

Where are triacylglycerols stored

Lipid droplets surrounded by a monolayer of phospholipids and proteins which are organelles for lipid metabolism metabolism

Triacylglycerols combine within cells forming

• 1: mobilization

• 2: activation & transport

• 3: breakdown into acetyl CoA

Peripheral tissues access lipid energy through the three stages of:

Triacylglycerols are broken into building components FA’s and glycerol

What happens in the stage 1: mobilization

FA’s are activated to enter the liver mitochondria for degradation

What happens in stage 2: activation and transport

FA’s go through step by step processes to form acetyl CoA which then enters the citric acid cycle

What happens in stage 3: breakdown into acetyl CoA

At the surface of the lipid droplet

The mobilization of triacylglycerols occurs

Epinephrine and glucagon

Hormones that induce FA degradation and regulate stores

• lipase

• 3 water (1 per each bond broken)

In stage 1, triacylglycerols are broken into 3 FA’s and glycerol through the use of

Albumin

FA’s are not water soluble so they must bind to … to travel through blood to tissues

Absorbed by the liver to use in glycolysis & gluconeogenesis

What happens to glycerol that is released in FA degradation

Fatty acid-transport proteins

Once FA & albumin reach the cell membrane FA is released and passes the membrane with the help of …

Fatty acid-binding proteins

Once within the cell FA’s move about with the help of

Reacting with coenzyme A to form Acyl CoA

FA’s become activated by

The outer mitochondrial membrane

Activation of FA’s occurs

• FA reacts with ATP forming acyl adenylate and PPi

• Acyl adenylate then reacts with coenzyme A to form

• Enzyme acyl CoA synthetase

• Reversible

The activation of FA’s reaction in stage 2

The hydrolysis of PPi to 2 phosphates using pyrophosphatase

The reactions in stage 2 are driver forward by

• Acyl CoA reacts with carnitine where the acyl group is transferred forming acyl carnitine and removing CoA

• Enzyme is carnitine acyltransferase I

Large chain FA’s are impermeable to the inner mitochondria membrane so

Translocase

Once formed acyl carnitine is shuttled across the membrane by

• CoA reforming acyl CoA within the matrix through the use of carnitine acyltransferase II

Once within the mitochondria matrix acyl carnitine losses the acyl group to …

• muscle cramping and weakness

• Muscle, kidney, heart

• Carnitine is in red meat

Deficiencies of carnitine, carnitine transferase or translocase can present as, effect, and be found in

• acetyl is 2 carbons

• Acyl is many carbons

Acetyl vs acyl CoA

• oxidation (FAD)

• Hydration

• Oxidation (NAD+)

• Thiolysis

Stage 3: breakdown occurs by the cycle of reactions:

2

Each cycle of reactions in stage 3 removes how many carbons

• left to the ketone

• Saturated (no DB)

Stage 3 is called the beta oxidation pathway as it happens at the beta carbon which is … and this stage only occurs on

Acyl CoA

Acyl CoA dehydrogenase

FAD to FADH2 ( reduced )

Trans delta squared enoyl CoA

Stage 3 step 1: oxidation process Reactant, enzyme, enzyme reaction, product

• trans DB

• 2-3

• The DB begins on C2

Trans delta squared enol CoA has a … DB between carbons … which is indicated by the delta squared representing …

Trans delta squared enoyl CoA

Enoyl CoA hydratase

Addition of water

L-3 hydroxyacyl CoA

Stage 3 step 2: hydration process Reactant, enzyme, enzyme reaction, product

• the DB between C2 and C#

• L isomer

Hydration in step 2 of stage 3 occurs on … which is stereospecific only forming

L-3 Hydroxyacyl CoA

L-3 hydroxyacyl CoA- dehydrogenase

NAD+ to NADH + H+

3-ketoacyl CoA

Stage 3 step 3: oxidation Reactant, enzyme, enzyme reaction, product

The hydroxyl group on c3 is converted to s keto group

In step 3 of stage 3 what occurs

3-ketoacyl CoA

Beta-ketothiolase

Thiol group of a coenzyme A enters

Acyl CoA (shortened by 2 C) + acetyl CoA

Stage 3 step 4: thiolysis/cleavage Reactant, enzyme, enzyme reaction, product

• 1 FAD, NAD, CoA, H2O for each bond broken

• 1 FADH2, NADH, and H+ per bond broken

• # of bonds broken +1 for number for acetyl CoA formed

For any saturated FA that goes through FA degradation, it will yield

• multiply number of NADH2 formed by 1.5

• Multiply number of NADH formed by 2.5

• Multiply number of acetyl CoA by 10

• Then subtract 2 from added number as 2 ATP are used in activation

To calculate number of ATPs generated from FA degradation