Lipid Metabolism-week 11

Question 1

How can we get the lipids absorbed into our body without them clogging our blood vessels?

Answer 1

1. Break down of Triglycerides by Lipases (break down triglycerides into simpler lipids)
2. Solubilize the lipids using Bile salts
3. Transport the lipids through the intestines
4. Transport lipids in the blood

Question 2

Where are bile salts made?

Answer 2

In the liver (amphipathic molecule) hydrophobic and hydrophilic

Similar structure to cholesterol because cholesterol is the building block for steroid hormones

Question 3

What are Bile salts?

Answer 3

Used to mix triglycerides

Question 4

How do Bile salts work?

Answer 4

Amphipathic molecule (hydrophobic and hydrophilic), hydrophobic molecule will bind to the lipid and the hydrophilic molecule will bind to the water molecule

Question 5

How are lipids transported through the intestine?

Answer 5

Pancreatic lipase breakdown the lipids in the intestine into smaller lipid products and the lipid products are solubilized by bile salts where the lipid products can cross the intestine

Question 6

How are lipids absorbed in the small intestines?

Answer 6

Triglycerides are
broken down by lipases into fatty acids and monoacylglycerols

Lipoproteins (Chylomicron) take over the function of the bile salts and allow the lipids to stay solubilized so it can be sent to other parts of the body

To the Lymph system

Question 7

How are lipids transported in the blood?

Answer 7

After being absorbed by the intestine, lipids go to tissues through the blood stream

They are too hydrophobic to go themselves so they are escorted by Apolipoproteins, these proteins bind the lipids and keep them soluble in the bloodstream

Question 8

Define the term lipoprotein:

Answer 8

Complex of lipids and apolipoprotein e.g chylomicron

Question 9

What are the 5 classes of lipoproteins?

Answer 9

Chylomicrons (transport cholesterol and lipids to tissues)
VLDL “ (very low density lipoprotein)
IDL “ (intermediate density lipoprotein)
LDL “ (low density lipoprotein)

HDL (transport cholesterol and lipids away from tissues, from tissues back to the liver, this is why higher ratio of HDLs is healthier because it counters build up of cholesterol in the body)

Question 10

Case study: Intracellular Transport of Cholesterol

How does cholesterol get transported into a cell?

Answer 10

Cholesterol, Major component of cell membrane, highly hydrophobic

1. Cholesterol (diet or made in body) is packaged into a Low density lipoprotein (LDL) complex
2. Low density lipoprotein (LDL) molecule is bound by LDL receptors on cell surface through the Apolipoprotein B-100 component
3. LDL receptor and molecule is internalized by cell membrane pits forming through recruitment of Clathrin proteins into Clathrin-coated vesicles.
   - cell membrane curves inward forming vesicles which pinch off and become internalized
4. Clathrin coated vesicles fuse with endosomes and Clathrin molecules go back to cell surface
5. Lower pH (5-6) causes release of LDL from LDL receptor
6. Endosome containing LDL fuses with Lysosome (contains proteases), and then the Apoliprotein B-100 portion is degraded and cholesterol released within lysosome
7. Cholesterol can either be converted to cholesteryl ester by Acyl-CoA Cholesterol Transferase (ACAT) or go to the endoplasmic reticulum
8. Increased levels of cholesterol in the endoplasmic reticulum signals the cells to make MORE Acyl-CoA Cholesterol Transferase (ACAT), and make LESS LDL Receptor and less Hydroxymethylglutaryl (HMG)-CoA Reductase

Question 11

Drugs can inhibit cholesterol synthesis:

What is the role of Statins?

Answer 11

Class of drugs (statins) can inhibit the enzyme HMG CoA reductase.

HMG CoA reductase is one of many enzymes in the cholesterol synthesis pathway.

Simvastatin, a popular statin drug prescribed for patients

Question 12

Summary of cholesterol transport from food into cells:

Answer 12

1. After digestion in the intestine, lipids are carried via lipoproteins through the circulatory system (bloodstream).
2. Cholesterol is packaged in the low density lipoprotein (LDL) and internalized into the cell
   - cells have a way to know if there is enough cholesterol already inside, which will result in stopping the transport and stopping the making of new cholesterol

Question 13

Metabolic breakdown of fatty acid:

Answer 13

Reactions in the breakdown (catabolism) of fatty acid

Energy carrying molecules produced by the reactions

Question 14

How do lipids metabolize after entering the cell?

Answer 14

Lipids move into the cytoplasm of the cell.

In order to extract energy from them (lipid metabolism)

the lipids must go into the mitochondria

Question 15

What is the rule for getting energy from fatty acids?

Answer 15

Rule: Longer fatty acids yield more energy than shorter fatty acids

Reason: Fatty acids are broken down by cycles or rounds of oxidation, and each round removes 2-carbon units. Therefore, the longer fatty acids can go through more cycles of oxidation

Question 16

How are fatty acids prepared for oxidation?

Answer 16

Fatty acids are prepared or “primed” with addition of CoA group by Acyl-CoA synthase

Question 17

Transport of Fatty Acyl-CoA into the mitochondrion:

Answer 17

Acyl-CoA is not permeable across the membrane cannot easily enter the molecule, therefore, cell has designed a way for it to enter by:

replacing the Acyl-CoA group with Carnitine to form Acyl-Carnitine (using the enzyme carnitine palmitoyl transferase I)

the mitochondria expresses the carnitine carrier protein (which allows anything attached to carnitine)

this allows the Acyl-Carnitine inside the mitochondria

in order to reverse the molecule back to Acyl-CoA they use an enzyme called (carnitine palmitoyl transferase II) which substitutes the carnitine with CoA

We now brought back Acyl-CoA

Question 18

Beta oxidation of fatty acids in the mitochondrion:

1st reaction

Answer 18

1st reaction of beta oxidation is catalyzed by Acyl-CoA dehydrogenase (removal of hydrogen) on Fatty Acyl-CoA

results in trans-Enoyl-CoA (hydrogen is removed from the carbon to form a double bond between 2 carbons in the chain)

hydrogens that are removed will carry electrons and transfer to FAD to form FADH2

energy carrying molecules will go to the electron transport chain and one of the molecules will generate 1 ATP

Question 19

Beta oxidation of fatty acids in the mitochondrion:

2nd and 3rd reaction

Answer 19

In the 2nd reaction
Enoyl-CoA hydratase is added to trans-Enoyl-CoA which makes 3-hydroxyacyl-CoA

In the 3rd reaction
3-hydroxlacyl-CoA dehydrogenase (HAD) catalyzes this reaction (removing hydrogens)
forming (beta) B-ketoacyl-CoA

NADH + H+ Electron transport chain
energy carrying molecules generate 2 ATPs

Question 20

Beta oxidation of fatty acids in the mitochondrion:

Last reaction of the cycle

Answer 20

(beta) B-ketoacyl-CoA, B-ketoacyl-CoA thiolase will add a CoA-SH to fatty acyl-CoA again and perform a cutting process (2 carbon atoms shorter)

Return to beginning of oxidation cycle to run through reactions again until the hydrocarbons are used up (back to reaction no. 1)

the carbons will become Acetyl-CoA
which will go through (oxidize) via the citric acid cycle and generate more NADHs and FADH2s

Question 21

Summary of Fatty acid Oxidation

Answer 21

Once inside the mitochondrion, cycles of oxidation break down the acyl-CoA molecule to yield FADH2 AND NADH, which feed into the electron transport chain reaction to make ATPs.

Each cycle removes 2 carbon atoms from acyl-CoA molecule to make acetyl-CoA, which feeds into the citric acid cycle to generate more FADH2 and NADH via oxidation

Question 22

What is the first step of synthesis of lipids?

Answer 22

The first step in the synthesis of both phospholipids for membranes and triacylglycerols for energy storage is the synthesis of phosphatidate
(diacylglycerol 3-phosphate)

Phosphatidate is formed by two acylation reactions starting from glycerol-3-phosphate

Question 23

Where does glycerol 3-phosphate come from?

Answer 23

Glycerol 3-phosphate is formed primarily by the reduction of dihydroxyacetone phosphate, an intermediate of the glycolysis pathway

Question 24

What occurs during synthesis of triacylglycerol synthesis?

Answer 24

1. ) The phosphatidate is hydrolyzed by a phosphatase (an enzyme that removes phosphate) to yield diacylglycerol (DAG)
2. ) The DAG is acylated (adding of acyl group) to triacylglycerol by the enzyme diacylglycerol acyltransferase (DGAT)

Question 25

Summary of topic:

Answer 25

Lipids such as cholesterol and triglyceride can be obtained from our diet or can be made by biochemical reactions in our body

There are different classes of lipoproteins that carry lipids throughout our body

Lipids such as fatty acids can be broken down and energy -carrying molecules such as NADH can be produced