Fatty Acid Oxidation and Ketogenesis

When youre hungry, fatty acids are released from ____ by. _____

triglycerols by hormone sensitive lipase

What kind of carbons are used for fatty acid oxidation?

Long chain fatty acids (16C or more)

From the cytosol, the fatty acid wants to move into the mitochondrial membrane. What is the first step to make this possible

In the cytosol, we must attach CoA through Fatty Acyl CoA synthetase and 2 ATP, creating fatty acyl coA. (Note: use of ATP leaves AMP, this step is irreversible)

From Fatty Acyl CoA, we are still not in the M Membrane because CoA cannot enter. How do we enter the M Membrane?

Remove CoA and replace with Carnitine through CAT-I

What is the rate limiting step of fatty acid oxidation transport

Fatty Acyl CoA to Fatty Acyl Carnitine using CAT-I and reverting back to Fatty Acyl CoA with CAT-II. This allows entrance into the membrane via carnitine and makes it stay as CoA

What would happen if a cell had an inability to produce acyl CoA dehydrogenase? Structure and physiological outcome.

A double bond would not form between the alpha and beta carbon of fatty acyl CoA. Person is unable to undergo fatty acid oxidation at the β-oxidation step

Why do we hydrate the double bond between the alpha and beta carbon of enoyl coA?

To break the double bond and leave a free hydroxyl group on beta carbon. Enzyme used for this reaction: Enoyl hydratase

A cell lacks beta-ketoacyl-CoA dehydrogenase. What step of beta oxidation is stopped?

the formation of beta ketoacyl CoA from beta hydroxyacyl CoA

Final products of fatty acid beta oxidation. Why are these products beneficial to the hungry human?

Fatty acyl CoA (14 carbons now) and Acytl CoA. We continually break down lipids because we don’t have access to sugar and we keep creating ATP via the ETC so our bodies can continue with its normal functions (heart beats, brain thinks, liver filters)

What is the total ATP generated from fatty acid oxidation? Show your work

108 ATP

What changes from fatty acid oxidation when we use an odd-numbered-position unsaturated fatty acid?

ODD:

1. 3 cycles of beta oxidation, shortens carbon chain and moves double bond between 3 and 4 carbon

2. use delta 3 delta 2-enoyl coA isomerase to move double bond between the 2 and 3 carbon

3. ready for beta oxidation

What changes from fatty acid oxidation when we use an even-numbered-position unsaturated fatty acid?

First half is the same as odd: move one double bond between carbons 2 and 3. To deal with the other double bond, 2,4-dienoyl reductase will remove the double bond attached to the 2 and 4 carbons. This moves the double bond to the middle of them (between 3 and 4) to be acted upon by enoyl-CoA isomerase, which moves the double bond back between carbons 2 and 3. Continue with beta oxidation.

What step of fatty acid oxidation is halted when we do not remove the second double bond from an even-numbered position saturated fatty acid?

Enoyl hydratase

Utilizing fatty acids with an odd number of

carbons and branched fatty acids produce ____ and leave behind _____ after beta oxidation .

Actyl CoA and propionyl-CoA

To break down propionyl-CoA into something we can use, what steps do we take?

1. Propionyl-CoA carboxylase will use ATP and HCO2 on the propionyl-CoA to make methylmalonyl coA

2. Methylmalonyl coA mutase will move structures around in methylmalonyl coA to make succinyl coA

3. Succinyl coA eventually becomes oxaloacetate and can create glucose through gluconeogenesis

Does fatty acid oxidation only occur in the mitochondria? Generates?

No, it can also occur in peroxisomes. (exclusive to 20 C or longer fatty acids) Generates Acetyl CoA and hydrogen peroxide. it’s.. not ideal.

The rate limiting step of ketogenesis is

The generation of HMG CoA from Acetoacetyl CoA via HMG CoA Synthase

What does HMG CoA lyase do to HMG CoaA? What are your products?

Cleaves a CoA and produces Acetoacetate, which will then produce beta-hydrxybutarate, and acetone (ALL KETONE BODIES!)

What prompts ketogenesis? What does this mean physiogically?

Excess acetyl coA. Our patient is can be fasting, doing keto diet, or undergoing ketoacidosis

What organ generates and utilizes ketone bodies? Why?

Our liver generates ketone bodies for the brain, heart, muscle, and kidney because our glucose levels are very low.

Where do you get ATP from?

Food! From your dietary fats.

You’re digesting a large, fatty meal after you have removed your gallbladder, and you experience discomfort. Why?

The gallbladder produces bile salts that break down your dietary fats, so without one you digest inefficiently.

What are chylomicrons?

Lipoproteins that can transport triglycerides and cholesterol through your body

A child is born with a defect in ApoC2. What does this tell you about how they digest food?

Once they create chylomicrons and have them sent into the bloodstream, they cannot be broken down and accumulate triglycerides in the blood.