Lipid Metabolism

What two main parts make up a fatty acid?

A carboxyl group and a long hydrocarbon chain.

Why are fatty acids important for lipids?

They are crucial for the formation of lipids, including triglycerides.

What causes a bend in a fatty acid chain?

A double bond in the hydrocarbon chain.

What is the difference between saturated and unsaturated fatty acids?

Saturated fatty acids have no double bonds and are straight; unsaturated fatty acids have at least one double bond, causing a bend.

What are the most abundant dietary lipids?

Triglycerides

What are essential fatty acids and where are they found?

Linoleic and linolenic acid; found in most vegetables and must be ingested because the body cannot make them.

What roles do fatty deposits in adipose tissue play?

They provide cushioning around organs, insulation under the skin, and a concentrated energy source.

What are the roles of dietary fats in the body?

• Help absorb fat-soluble vitamins (A, D, E, K)

• Serve as a major energy source for liver and muscle

  • Are components of myelin sheaths and cell membranes

What are Prostaglandins

fatty acid-based molecules that act like local hormones

What are the functions of prostaglandins?

Smooth muscle contraction, Control of blood pressure, Inflammation

What roles does cholesterol play in the body?

Stabilizes cell membranes, Precursor of bile salts, Precursor of steroid hormones, It is a hydrophobic lipid

What structural materials does the liver synthesize in lipid metabolism?

Lipoproteins (for cholesterol and fat transport), Tissue factor (a clotting factor), Cholesterol from acetyl CoA, Bile salts (from cholesterol)

How do endocrine organs use cholesterol?

They synthesize steroid hormones from cholesterol.

Is cholesterol hydrophobic or loving water

hydrophobic

What are lipids

fatty, oily, or waxy molecules that do not dissolve in water. They're made mostly of carbon, hydrogen, and oxygen.

What are the two main categories of lipids in the body?

1. Storage lipids (neutral)

2. Membrane lipids (polar)

What is the structure of a triacylglycerol (storage lipid)?

3-carbon glycerol backbone, 3 fatty acids, Used to store energy in fat cells

What does it mean when a lipid is amphipathic?

It has both polar (hydrophilic) and non-polar (hydrophobic) parts.

What are the two main types of phospholipids?

1. Glycerophospholipids: glycerol + 2 fatty acids + phosphate + alcohol

2. Sphingolipids: sphingosine + 1 fatty acid + phosphate + choline

What is the role of glycolipids in the membrane?

1. Cell recognition

2. Cell signaling

What are the two types of glycolipids?

• Sphingolipids: sphingosine + fatty acid + sugar

• Galactolipids: glycerol + 2 fatty acids + sugar (± sulfate)

What is unique about archaeal ether lipids?

1. Found in archaebacteria

2. Use ether linkages instead of ester

3. Structure: glycerol + diphytanyl chains + phosphate

Why are membrane lipids important?

• They form the cell membrane

• Allow selective transport

• Help maintain fluidity and cell signaling

How are fatty acids attached to glycerol in a triglyceride?

By ester bonds

What is the structure of glycerol?

CH₂OH–CHOH–CH₂OH

How are glycerol and fatty acids metabolized?

1. They are metabolized in distinct ways

2. Glycerol enters glycolysis, and fatty acids undergo beta-oxidation

What major metabolic processes occur in the cytosol (outside mitochondria)?

glycolysis, PPP, Fatty Acid Synthesis

What major metabolic processes occur in the mitochondrial matrix?

Citric Acid Cycle, Oxidative Phosphorylation, beta-oxidation of Fatty acids, Ketone Body formation

What happens in both the mitochondrial matrix and cytosol

Urea Synthesis, Glucogensis

What are the 3 sources of fatty acid fuel for cells?

Fats consumed in the diet, Fats stored in cells as lipid droplets, Fats synthesized in one organ and exported to another

What are lipid droplets?

Lipid droplets are storage sites inside cells where fats are concentrated and held for later use as energy.

How are most fat metabolism products transported in the body?

They are transported in lymph as chylomicrons, which are special lipoprotein structures.

What happens to lipids in chylomicrons?

They are hydrolyzed by plasma enzymes and then absorbed by cells.

What type of fats are routinely used for energy?

Neutral fats (like triglycerides) are the main source of fats that are oxidized for energy.

What are the two separate pathways for fat catabolism?

• Glycerol pathway

• Fatty acid pathway

What is the role of bile salts in fat digestion?

They emulsify dietary fats in the small intestine, forming mixed micelles.

What does it mean that bile salts "emulsify dietary fats" and form mixed micelles?

Bile salts break large fat droplets into smaller ones in the small intestine (emulsification), allowing fats to mix with water. They then surround the small fat pieces to form micelles, which help enzymes digest the fats and make absorption easier.

What happens to triacylglycerols in the intestine?

They are broken down by intestinal lipases.

What happens after lipids are broken down in the intestine?

1. Fatty acids and breakdown products are absorbed by intestinal mucosa.

   1. They are reassembled into triacylglycerols.

How are triacylglycerols transported after absorption?

They are packed with cholesterol and apolipoproteins into chylomicrons.

How do chylomicrons reach tissues?

They move through the lymphatic system and bloodstream to reach tissues.

What does lipoprotein lipase do?

It breaks down triacylglycerols in chylomicrons into fatty acids and glycerol (activated by ApoC-II).

What happens to fatty acids after entering cells?

They are either oxidized for energy or re-esterified for storage in myocytes or adipocytes.

First step of fatty acid catabolism?

Mobilization: Triglycerides are broken down into fatty acids and glycerol and released from adipose tissue.

Second step of fatty acid catabolism?

Activation & Transport: Fatty acids are activated and transported into mitochondria.

Third step of fatty acid catabolism?

Breakdown: Fatty acids are broken down step-by-step into acetyl-CoA, which enters the Krebs/TCA cycle.

What does "mobilization of triglycerides" mean?

It refers to the process of breaking down stored triglycerides into free fatty acids and glycerol, which can then be used for energy.

What hormone signaling pathway leads to triglyceride mobilization?

1. A hormone binds to a 7TM receptor

2. This activates adenylate cyclase, which makes cAMP

3. cAMP activates protein kinase

4. Protein kinase activates triacylglycerol lipase, which breaks down triglycerides into fatty acids and glycerol

What triggers the mobilization of triglycerides in adipose tissue?

Low blood glucose levels stimulate glucagon release, which starts the process.

How does glucagon lead to triglyceride breakdown?

1. Glucagon binds to a G-protein-coupled receptor

2. Activates adenylate cyclase, which produces cAMP

3. cAMP activates PKA

4. PKA phosphorylates perilipin and activates hormone-sensitive lipase (HSL)

What happens once hormone-sensitive lipase is activated?

It breaks down triglycerides into fatty acids and glycerol, which are released into the bloodstream and transported to other cells (like muscle) for energy.

What is the role of hormone-sensitive lipase?

It hydrolyzes triglycerides into glycerol and three fatty acids during fat mobilization.

How is hormone-sensitive lipase regulated?

• Glucagon activates HSL

• Insulin inactivates HSL

What is the purpose of activating fatty acids?

To convert them into a form (fatty acyl-CoA) that can enter mitochondria for breakdown.

What is the reaction for fatty acid activation?

Fatty acid + CoA + ATP → fatty acyl-CoA + AMP + 2Pi
(This is an exergonic reaction and requires ATP)

What enzyme activates fatty acids?

Fatty acyl-CoA synthetase

How do fatty acids get into the mitochondrial matrix?

1. Fatty acyl-CoA is converted to acyl-carnitine

2. Acyl-carnitine is transported into the mitochondria by translocase

3. Once inside, it's converted back to fatty acyl-CoA

What is the role of carnitine in fatty acid transport?

Carnitine carries fatty acids across the mitochondrial membranes by forming acyl-carnitine complexes.

Which enzymes are involved in carnitine-mediated fatty acid transport?

1. Carnitine acyltransferase I (outer membrane)

2. Carnitine acyltransferase II (inner membrane)

what is the first stage of fatty acid oxidation?

β-oxidation of fatty acids

what is the second stage of fatty acid oxidation?

Acetyl-CoA is oxidized to CO₂ in the citric acid cycle

what is the third stage of fatty acid oxidation?

Electrons from NADH/FADH₂ go to the electron transport chain (ETC) to make ATP

What happens during β-oxidation?

Fatty acid chains are broken down, removing 2-carbon units each round to produce acetyl-CoA

What does acetyl-CoA do after β-oxidation?

It enters the citric acid cycle and gets fully oxidized to CO₂

What is the role of NADH and FADH₂ in fatty acid oxidation?

They carry electrons to the electron transport chain, where ATP is produced

What kind of fatty acids undergo regular β-oxidation?

Even-numbered, saturated fatty acids

what is the 4-step repetitive cycle of β-oxidation?

1. Oxidation

2. Hydration

3. Oxidation

4. Thiolysis

What is produced in each round of β-oxidation?

1 molecule of acetyl-CoA (2-carbon unit)

• NADH and FADH₂ (electron carriers)

What does thiolysis do in fatty acid breakdown?

It cleaves the β-ketoacyl-CoA, releasing an acetyl-CoA and a shortened acyl-CoA chain.

What is an example of fatty acid oxidation?

Oxidation of palmitate (C16) produces 8 acetyl-CoA molecules

What is the key intermediate formed after the first oxidation step in β-oxidation?

trans-Δ²-enoyl-CoA

How many total ATP are produced from the complete oxidation of one palmitoyl-CoA molecule?

108

How is ATP generated during fatty acid oxidation?

ATP comes from:

1. FADH₂ (1.5 ATP each)

2. NADH (2.5 ATP each)

3. Direct GTP/ATP production (e.g., from Succinyl-CoA synthetase)

What enzyme is required for β-oxidation of monounsaturated fatty acids?

Enoyl-CoA isomerase

How does a double bond affect ATP yield in monounsaturated fatty acid oxidation?

You lose 2 ATP per double bond.

Why is enoyl-CoA isomerase needed in monounsaturated fatty acid oxidation?

It converts cis double bonds into trans configuration so β-oxidation can proceed.

What additional enzyme is required for polyunsaturated fatty acid oxidation?

2,4-dienoyl-CoA reductase (in addition to enoyl-CoA isomerase)

How much ATP is lost per additional double bond in polyunsaturated fatty acids?

You lose 3 ATP per additional double bond.

How does the oxidation of odd-chain fatty acids differ from even-chain fatty acids?

It proceeds like even-chain FA oxidation but ends with a 3-carbon propionyl-CoA, which is converted to succinyl-CoA.

What is propionyl-CoA converted into during odd-chain FA oxidation?

Succinyl-CoA, which enters the TCA (Krebs) cycle

What cofactors are needed to convert propionyl-CoA to succinyl-CoA?

• Biotin (for carboxylation step)

• Vitamin B₁₂ (coenzyme for methylmalonyl-CoA mutase)

What is lipogenesis?

The process of converting excess glucose, glycerol, and fatty acids into triglycerides for fat storage.

Why can glucose easily be converted to fat?

Because acetyl-CoA, a glucose breakdown intermediate, is the starting molecule for fatty acid synthesis.

What is lipolysis?

Lipolysis is the breakdown of stored fat, essentially the reverse of lipogenesis.

What molecule is required for the complete oxidation of fat?

Oxaloacetate

What happens when oxaloacetate levels drop during fat metabolism?

Acetyl-CoA is converted into ketone bodies (ketogenesis).

What does lipolysis break triglycerides into?

Glycerol and fatty acids.

What happens to glycerol after lipolysis?

It enters glycolysis.

What happens to fatty acids after lipolysis?

They undergo β-oxidation to form acetyl-CoA.

What are the three main fates of acetyl-CoA?

• Enters the Krebs cycle to produce ATP

• Used in ketogenesis (during fasting)

• Converted into cholesterol → steroids and bile salts

Why is glucose easily converted into fat?

Because acetyl-CoA, produced from glucose metabolism, is the starting molecule for fatty acid synthesis.

What are the two key enzymes for coordinating fatty acid synthesis and degradation?

Acetyl-CoA carboxylase (ACC) and Carnitine acyltransferase I.

What does ACC do in fatty acid metabolism?

It catalyzes the formation of malonyl-CoA, the first step in fatty acid synthesis.

What does Carnitine acyltransferase I do?

It regulates transport of fatty acids into the mitochondrial matrix for β-oxidation.

What happens in the body after a high-carb meal regarding fat metabolism?

Insulin is released, activates phosphatase which dephosphorylates and activates ACC, increasing malonyl-CoA which inhibits fatty acid entry into mitochondria.

How does the body regulate fat metabolism when blood glucose drops?

Glucagon activates PKA, which phosphorylates and inactivates ACC. Malonyl-CoA levels drop, allowing fatty acids to enter mitochondria for oxidation.