- Specialized carrier that transports long-chain Acyl groups from Cytosol into the Mitochondrial Matrix - Obtained from the diet (primarily meat products)

- Branched chain fatty acid, product of chlorophyll metabolism

Lipid Mobilization and Oxidation Flashcards by Alex Thomas

Where does dietary lipid digestion occur?

It begins in the stomach and continues in the small intestine

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Where and how are Cholesteryl Esters, Phospholipds, and Triacylglycerols with long-chain fatty acids degraded?

In the small instestine by pancreatic enzymes

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What are the important pancreatic enzymes?

Cholesterol Esterase
Phospholipase A2
Pancreatic Lipase

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How does Cystic Fibrosis affect the pancreatic enzymes?

Thickened mucus prevents these enzymes from reaching the intestine

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How is TAG from milk fat degraded?

TAG in milk contains short- to medium-chain-length FAs and are degraded in the stomach by Acid Lipases (Lingual Lipase and Gastric Lipase)

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Why, where, and how does emulsification occur?

Why: hydrophobic nature of lipids requires them to be emulsified for efficient degradation
Where: Small intestine
How: Peristaltic action (mechanical mixing) and Bile Salts (Detergents)

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What are the 3 primary products of dietary lipid degradation?

) 2-monoacylglycerol
) Cholesterol (nonesterified/free)
) Free FA

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What forms Mixed Micelles?

Why are they important?

The 3 primary products of dietary lipid degradation + fat-soluble vitamins
Facilitate dietary lipid absorption by Intestinal Mucosal Cells (Enterocytes)

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Chylomicrons

Lipoprotein (lipid and protein) comprised of TAG, Cholesteryl Esters, and Apolipoprotein (apo) B-48 assembled with fat-soluble vitamins inside the Intestinal Mucosal Cells (Enterocytes)

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What type of FAs enter the blood directly?

Short- and medium-chain FAs

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How do Chylomicrons enter the blood?

They first enter into the Lymph and then enter the blood

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Where and how are Chylomicrons degraded?

In the Capillaries of Muscle and Adipose tissue by Lipoprotein Lipase (with Apo C-II coenzyme)

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What is Fat Maldigestion and what does it cause?

Malabsorption which causes Steatorrhea (lipids in the feces)

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Carnitine

Specialized carrier that transports long-chain Acyl groups from Cytosol into the Mitochondrial Matrix
Obtained from the diet (primarily meat products)

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Phytanic Acid

Branched chain fatty acid, product of chlorophyll metabolism

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How many carbons do Short Chain Fatty Acids (SCFAs) have?

2-5 carbons

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How many carbons do Medium Chain Fatty Acids (MCFAs) have?

6-12 carbons

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How many carbons do Long Chain Fatty Acids (LCFAs) have?

13+ carbons

What are the fat soluble vitamins?

A, D, E, K

How do Polyunsaturated Fats impact health?

Precursor to Hormones (Ex. Prostaglandins)

- Reduce Total and LDL Cholesterol (Lower Heart Disease)

Prostaglandins

Hormone
Polyunsaturated Fats are a precursor to
Stimulate Endothelial Cells that line blood vessels to release Nitric Oxide (Vasodilator, lowers BP)

Nitric Oxide

Vasodilator, released by Endothelial Cells when stimulated by Prostaglandins
Lowers BP

Preferred energy source in the body

Carbohydrates > Fats > Proteins > Ketone Bodies

Where, when, and how are Ketone Bodies produced?

In the Liver Mitochondria
Made during prolonged Fasting or Exercise
Made with Type 1 DM or Alcoholism
Made by using Acetyle-CoA

How are Ketone Bodies used as energy?

- Ketone Bodies are released from the Liver into the blood - Can be picked up by the majority of cells - Reconverted to Acetyl-CoA in the cell - Acetyle-CoA enters the mitochondria to produce ATP

What are the 3 main Ketone Bodies?

- Acetoacetate - B-Hydroxybutyrate - Acetone

Fasting timeline

1. ) 12 hours: Glycogenolysis (Pancreas releases Glucagon --> Liver breaksdown Glycogen to Glucose) 2. ) 24 hours: Gluconeogenesis (Liver makes new glucose) 3. ) 1-3 days: Breakdown of fatty acids for energy: Fatty Acids --> (B-Oxidation) --> Acetyl-CoA (Except for Brain Cells, FAs can't cross Blood Brain Barrier, Brain Cells can only use Glucose or Ketone Bodies for energy)

Why use Acetyl-CoA for Ketone Body production?

- In a starvation state, low levels of Oxaloacetate (normally Acetyl-CoA + Oxaloacetate --> Citrate in TCA cycle) - When low levels of Oxaloacetate, Acetyle-CoA builds up - Liver uses this build up to make Ketone Bodies

1st step of Ketone Body production

2x Acetyle-CoAs --> (Acetyl-CoA Acyl-Transferase) --> Acetoacetyl-CoA + Free CoA

2nd step of Ketone Body production

Acetoacetyl-CoA + Ac-CoA --> (HMG-CoA Synthase) --> 3-Hydroxy-3-Methylglutaryl-CoA + Free CoA Note: This is the rate limiting step

What is the rate limiting step of Ketone Body production?

The second step: | Acetoacetyl-CoA + Ac-CoA --> (HMG-CoA Synthase) --> (AKA HMG-CoA) + Free CoA

3rd step of Ketone Body production

HMG-CoA --> (HMG-CoA Lyase) --> Acetoacetate (Ketone Body + Ac-CoA

Possible 4th step of Ketone Body

Acetoacetate (Ketone Body) --> (B-Hydroxybuteryate Dehydrogenase) --> B-Hydroxybuterate (Another Ketone Body)

How is Acetone made?

Some Acetoacetate (Ketone Bodies) in the blood spontaneously lose a carbon and become Acetone (Metabolically useless Ketone Body, exhaled from lungs)

What Ketone Body is useless? What implication does this have?

Acetone --> Gets exhaled from the lungs --> Explains Fruity Smelling Breath in Diabetic Ketoacidosis

What happens to the blood pH as a result of Ketone Bodies being in the blood?

- Ketone Bodies are Acids --> Lowers Blood pH | - Metabolic Acidosis

What cells can't use Ketone Bodies (Acetoacetate and B-Hydroxybutyrate) for energy and why?

- Red Blood Cells because they don't have Mitochondria | - Liver cells because they don't have the Enzyme Thiophorase which converts Acetoacetate to Acetoacetyl-CoA

How is B-Hydroxybutyrate converted back to Acetoacetate one in the peripheral tissues?

- Enzyme B-Hydroxybutyrate Dehydrogenase | - Makes an NADH in the process

How is Acetoacetate used as energy in the cells?

Acetoacetate + [Succinyl-CoA] --> (Thiophorase) --> Acetoacetyl-CoA + [Succinate] Acetoacetyl-CoA --> (B-Ketothiolase) --> 2x Acetyl-CoAs + [CoA] Acetyl-CoA can now enter TCA Cycle to make ATP

What hormone induces Triglyceride breakdown in Adipocytes?

Hormone Sensitive Lipase (HSL)

What is the role of the protein Albumin?

Carries fatty acids to target cells, like Live Cells, which are capable of fatty acid oxidation

Step 1 of fatty acid oxidation

Once inside the target cell: FA --> (Fatty Acyl-CoA Synthetase uses 2 ATP) --> Fatty Acyl-CoA

Where are the enzymes required for B-oxidation of fatty acids?

In the Mitochondrial Matrix

Step 2 of fatty acid oxidation

Fatty Acyl-Coa --> (CPT-1 aka CAT-1) --> Fatty Acyl-Carnitine