Lipid Metabolism

Triacylglycerols (TAGs)

What is the primary component of dietary lipids, making up 98% of them?

No

Do salivary enzymes in the mouth have any effect on lipids, specifically triacylglycerols (TAGs)?

Chyme

What physical transformation do most, not all triacylglycerols (TAGs) undergo in the stomach, resulting in small globules or droplets known as what?

Physical

Is the transformation of most triacylglycerols (TAGs) into small globules or droplets called chyme in the stomach a physical or chemical process?

Stomach

Where does lipid digestion start?

10%

Lipid Digestion in the Stomach

Approximately what percentage of TAGs are hydrolyzed in the stomach during lipid digestion?

Gastric lipase enzymes

Lipid Digestion in the Stomach

What enzymes in the stomach hydrolyze TAG ester bonds?

Emulsified with bile salts

Lipid Digestion in the Intestinal Cells

What happens to chyme when it enters the small intestine in the context of lipid digestion?

Pancreatic lipase

Lipid Digestion in the Intestinal Cells

Which enzyme hydrolyzes ester bond linkages between fatty acid units and glycerol

Micelles

Lipid Digestion in the Intestinal Cells

What is formed when fatty acids, monoacylglycerols, and bile salts combine in lipid digestion?

Monoacylglycerols; Free fatty acids

Lipid Digestion in the Intestinal Cells

In the intestinal cells, (?) and (?) are repackaged to form TAGs

Chylomicrons

Lipid Digestion in the Intestinal Cells

These new TAGs combine with membrane lipids (phospholipids and cholesterol) and water-soluble proteins to form?

Chylomicrons

What do you call the lipoproteins that transport TAGs from intestinal cells, via the lymphatic system, to the bloodstream?

Short-chain; Medium-chain; Long-chain

Enumerate the 3 types of fatty acids

Enterocytes

Short- and medium-chain fatty acids enter portal blood directly from?

Albumin

Short- and medium-chain fatty acids are bound to (?) in blood

Liver

Short- and medium-chain fatty acids are oxidized in (?) or elongated and used for triglyceride formation

Chylomicrons

Long-chain fatty acids form what?

Lacteals

Long-chain fatty acids drain into the lymphatics via the?

12

True or False? If false, replace the underlined word to make the statement correct.

“Long-chain fatty acids have more than 15 Carbons.”

Mouth

LIPID DIGESTION

Identify Step 1

Mouth; Stomach; Small Intestine; Intestinal Cells; Lymphatic System; Bloodstream

Enumerate in order, the organs that lipid digestion goes through

Stomach

LIPID DIGESTION

Identify Step 2

Skin

Adipose tissue is located beneath the (?), especially in the abdominal region and vital organs

Small Intestine

LIPID DIGESTION

Identify Step 3

heat loss; physical shock

Adipose tissue serves as an insulator against (?) and protection against (?)

Intestinal Cells

LIPID DIGESTION

Identify Step 4

Adipose Tissue

Largest cells in the body where the cytoplasm is replaced with large TAG droplets

Beta Oxidation

What is the catabolic process by which fatty acid molecules are broken down to generate acetyl-CoA, which enters the citric acid cycle, and NADH and FADH2, which are co-enzymes used in the electron transport chain

Lymphatic System

LIPID DIGESTION

Identify Step 5

Dihydroxyacetone phosphate (DHAP)

Glycerol Metabolism

What is glycerol, after entering the bloodstream, converted to in the liver or kidney?

Phosphorylation; primary

Glycerol Metabolism

Step 1: (?) of (?) hydroxyl group of the glycerol

Oxidization; secondary

Glycerol Metabolism

Step 2: (?) of (?) alcohol group of glycerol to a ketone

Muscle and Liver

Beta Oxidation

Where does it occur?

Tissues that can use fatty acids as energy source, primarily in the 2 organs?

Bloodstream

LIPID DIGESTION

Identify Step 6

Cytosol

Beta Oxidation

Where does it occur?

Fatty acid activation occurs in the (?)

Mitochondria; Peroxisomes

Beta Oxidation

Where does it occur?

β-oxidation occurs in the (?) and (?)

Fatty Acids (Palmitic acid and Linoleic acid)

What are the substrates involved in Beta Oxidation?

Acetyl-CoA; NADH; FADH2; Propionyl CoA

What are the products of Beta Oxidation?

Odd-numbered

Beta Oxidation

Prioponyl CoA is for (?) Carbon fatty acids

Mitochondria

Beta Oxidation

Which step is rate-limiting?

Translocation of fatty Acyl CoA from the cytosol to the (?)

Carnitine-palmitoyl transferase

Beta Oxidation

Which enzyme is involved in the translocation of fatty Acyl CoA from the cytosol to the mitochondria?

A

Beta Oxidation

➢ "Priming" of fatty acids for reaction

➢ ATP-dependent acylation to form fatty Acyl-CoA

➢ Enzyme: Acyl-CoA synthetases (thiokinases)

A.) Step 1: Fatty acid activation

B.) Step 2: Transport of fatty Acyl-CoA across the mitochondrial membrane

C.) Step 3: Degradation of fatty Acyl-CoA

Acyl-CoA synthetases (thiokinases)

Beta Oxidation

What enzyme is involved in Step 1: Fatty Acid Activation?

Carnitine palmitoyltransferases I and II

Beta Oxidation

What enzyme is involved in Step 2: Transport of fatty Acyl-CoA across the mitochondrial membrane?

B

Beta Oxidation

➢ Transfer of acyl portion to carnitine

➢ Mediated by specific carrier protein

➢ Enzymes involved:

carnitine palmitoyltransferases I and II

A.) Step 1: Fatty acid activation

B.) Step 2: Transport of fatty Acyl-CoA across the mitochondrial membrane

C.) Step 3: Degradation of fatty Acyl-CoA

C

Beta Oxidation

➢ Four reactions repeatedly cleave two carbon units from the carboxyl end of the acyl CoA molecule

➢ This process is also called β-oxidation pathway because the second carbon or beta carbon from the carboxyl end of the chain is oxidized.

A.) Step 1: Fatty acid activation

B.) Step 2: Transport of fatty Acyl-CoA across the mitochondrial membrane

C.) Step 3: Degradation of fatty Acyl-CoA

C

Beta Oxidation

Oxidation → Hydration → Oxidation → Thiolysis

A.) Step 1: Fatty acid activation

B.) Step 2: Transport of fatty Acyl-CoA across the mitochondrial membrane

C.) Step 3: Degradation of fatty Acyl-CoA

Oxidation; Hydration; Oxidation; Thiolysis

Beta Oxidation

Enumerate the steps in Step 3: Degradation of Fatty Acyl-CoA

FAD; FADH2

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

In Step 1: Oxidation/Dehydrogenation,

The oxidizing agent is (?)

The product is (?)

A

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

➢ Hydrogen atoms removed from α and β carbons, forming a double bond between them

➢ FAD serves as the oxidizing agent, producing an FADH2 molecule

A.) Step 1: Oxidation/Dehydrogenation

B.) Step 2: Hydration

Acyl Coa dehydrogenase

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

In Step 1: Oxidation/Dehydrogenation,

What is the enzyme involved?

Enoyl CoA hydralase

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

In Step 2: Hydration

What is the enzyme involved?

B

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

➢ A molecule of water is added across the trans double bond, producing a secondary alcohol at the β-carbon position

A.) Step 1: Oxidation/Dehydrogenation

B.) Step 2: Hydration

C

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

➢ This step requires NAD+ as a coenzyme.

➢ The two hydrogens and electrons removed are transferred to the NAD+ to form NADH+ and H+.

➢ Secondary alcohol is oxidized to a ketone at the beta carbon.

C.) Step 3: Oxidation/Dehydrogenation

D.) Step 4: Thiolysis

NAD+

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

In Step 3: Oxidation/Dehydrogenation

Which coenzyme is required?

B-Hydroxyacyl CoA dehydrogenase

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

In Step 3: Oxidation/Dehydrogenation

Which enzyme is involved?

2

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

In Step 4: Thiolysis,

The new Acyl CoA molecule is shorter by how many carbon atoms than its predecessor?

D

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

➢ Fatty acid chain is broken between the α and β carbons by

reaction with a coenzyme A molecule.

➢ The result is an acetyl CoA molecule and a new acyl CoA molecule that is shorter by two carbon atoms than its predecessor

C.) Step 3: Oxidation/Dehydrogenation

D.) Step 4: Thiolysis

Thiolase

Beta Oxidation – Step 3: Degradation of Fatty Acyl-CoA

In Step 4: Thiolysis,

What is the enzyme involved?

2

Beta Oxidation – Unsaturated Fatty Acids

Oxidation of unsaturated fatty acids differs to saturated fatty acids because it requires how many ADDITIONAL STEPS?

A

A.) Step 1: Oxidation/Dehydrogenation

B.) Step 2: Hydration

C.) Step 3: Oxidation/Dehydrogenation

D.) Step 4: Thiolysis

B

A.) Step 1: Oxidation/Dehydrogenation

B.) Step 2: Hydration

C.) Step 3: Oxidation/Dehydrogenation

D.) Step 4: Thiolysis

C

A.) Step 1: Oxidation/Dehydrogenation

B.) Step 2: Hydration

C.) Step 3: Oxidation/Dehydrogenation

D.) Step 4: Thiolysis

D

A.) Step 1: Oxidation/Dehydrogenation

B.) Step 2: Hydration

C.) Step 3: Oxidation/Dehydrogenation

D.) Step 4: Thiolysis

Epimerase

Beta Oxidation – Unsaturated Fatty Acids

Which enzyme changes D configuration to an L configuration?

Cis-trans isomerase

Beta Oxidation – Unsaturated Fatty Acids

Which enzyme produces a trans-(2,3) double bond from a cis-(3,4) double bond

21

ATP Yield of Palmitate

Identify the ATP yield (A)

14

ATP Yield of Palmitate

Identify the ATP yield (B)

96

ATP Yield of Palmitate

Identify the ATP yield (C)

-2

ATP Yield of Palmitate

Identify the ATP yield (D)

129

ATP Yield of Palmitate

Identify the ATP yield (E)

carbohydrate; lipid metabolism

Beta Oxidation

Adequate balance in (?) and (?) is required

fat; carbohydrates

Lipid–carbohydrate metabolism can be disturbed by the following conditions:

Dietary intake is high in (?) and low in (?)

Diabetic conditions

Lipid–carbohydrate metabolism can be disturbed by the following conditions:

(?) where the body cannot use glucose properly

fasting

Lipid–carbohydrate metabolism can be disturbed by the following conditions:

Prolonged (?) conditions

Ketogenesis

Involves the synthesis of ketone bodies from acetyl CoA

Ketone bodies

What are the water-soluble molecules containing the ketone group that are produced by the liver from fatty acids?

liver mitochondria

Where is the primary site for Ketogenesis?

Ketone bodies

What is produced by the liver when you don't eat much, follow low-carb diets, starve, exercise intensely, drink too much alcohol, or have untreated type 1 diabetes.

Acetoacetate; β-hydroxybutyrate; Acetone

Enumerate the 3 ketone bodies

Thiolase

Ketogenesis

In Step 1: First condensation, which enzyme is involved?

A

Ketogenesis

➢ Two acetyl CoA molecules combine

➢ Reversal of the last step of the β-oxidation pathway

➢ Result: Acetoacetyl CoA

A.) Step 1: First condensation

B.) Step 2: Second condensation

HMG-CoA synthase

Ketogenesis

In Step 2: Second condensation, which enzyme is involved?

B

Ketogenesis

➢ Acetoacetyl CoA + Third Acetyl CoA + Water → 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) + CoA–SH

A.) Step 1: First condensation

B.) Step 2: Second condensation

HMG-CoA lyase

Ketogenesis

In Step 3: Chain cleavage, which enzyme is involved?

C

Ketogenesis

➢ hahaha

C.) Step 3: Chain cleavage

D.) Step 4: Hydrogenation

D-B-hydroxybutyrate dehydrogenase

Ketogenesis

In Step 4: Hydrogenation, which enzyme is involved?

Complex

Lipogenesis - Step 2: Fatty Acid Synthase Complex

Fatty acid formation is made efficient as all reactions because the process takes place within the?

D

Ketogenesis

➢ Acetoacetate is reduced to β-hydroxybutyrate

C.) Step 3: Chain cleavage

D.) Step 4: Hydrogenation

Lipogenesis

It is the process of converting protein into fatty acids

Mitochondria

Lipogenesis - Step 1: Conversion of Acetyl CoA to Malonyl CoA

Acetyl CoA is generated in which organelle?

Acetyl CoA

What is the starting material for lipogenesis?

Cancer

Enhanced lipogenesis is a characteristic feature of which sickness?

Tumor cell

Enhanced Lipogenesis

Which cell’s survival is influenced by deregulated lipid biosynthesis?

Cytosol

Lipogenesis - Step 1: Conversion of Acetyl CoA to Malonyl CoA

Once the Acetyl CoA is generated in mitochondria, it must first be transported where?

acyl carrier protein (ACP-SH)

Lipogenesis - Step 2: Fatty Acid Synthase Complex

All intermediates in fatty acid synthesis are linked to (?)

acyl carrier protein (ACP-SH)

Lipogenesis - Step 2: Fatty Acid Synthase Complex

(?) can be regarded as a “giant CoA molecule”

Malonyl CoA; palmitate

Lipogenesis - Step 2: Fatty Acid Synthase Complex

(?) is elongated by the FAS complex to produce (?)

Highly proliferating

Enhanced Lipogenesis

Leads to a continuous supply of fatty acids for membrane production of which type of cells?