Lipid Metabolism-week 11 Flashcards
(25 cards)
How can we get the lipids absorbed into our body without them clogging our blood vessels?
- Break down of Triglycerides by Lipases (break down triglycerides into simpler lipids)
- Solubilize the lipids using Bile salts
- Transport the lipids through the intestines
- Transport lipids in the blood
Where are bile salts made?
In the liver (amphipathic molecule) hydrophobic and hydrophilic
Similar structure to cholesterol because cholesterol is the building block for steroid hormones
What are Bile salts?
Used to mix triglycerides
How do Bile salts work?
Amphipathic molecule (hydrophobic and hydrophilic), hydrophobic molecule will bind to the lipid and the hydrophilic molecule will bind to the water molecule
How are lipids transported through the intestine?
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
How are lipids absorbed in the small intestines?
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
How are lipids transported in the blood?
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
Define the term lipoprotein:
Complex of lipids and apolipoprotein e.g chylomicron
What are the 5 classes of lipoproteins?
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)
Case study: Intracellular Transport of Cholesterol
How does cholesterol get transported into a cell?
Cholesterol, Major component of cell membrane, highly hydrophobic
- Cholesterol (diet or made in body) is packaged into a Low density lipoprotein (LDL) complex
- Low density lipoprotein (LDL) molecule is bound by LDL receptors on cell surface through the Apolipoprotein B-100 component
- 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 - Clathrin coated vesicles fuse with endosomes and Clathrin molecules go back to cell surface
- Lower pH (5-6) causes release of LDL from LDL receptor
- Endosome containing LDL fuses with Lysosome (contains proteases), and then the Apoliprotein B-100 portion is degraded and cholesterol released within lysosome
- Cholesterol can either be converted to cholesteryl ester by Acyl-CoA Cholesterol Transferase (ACAT) or go to the endoplasmic reticulum
- 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
Drugs can inhibit cholesterol synthesis:
What is the role of Statins?
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
Summary of cholesterol transport from food into cells:
- After digestion in the intestine, lipids are carried via lipoproteins through the circulatory system (bloodstream).
- 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
Metabolic breakdown of fatty acid:
Reactions in the breakdown (catabolism) of fatty acid
Energy carrying molecules produced by the reactions
How do lipids metabolize after entering the cell?
Lipids move into the cytoplasm of the cell.
In order to extract energy from them (lipid metabolism)
the lipids must go into the mitochondria
What is the rule for getting energy from fatty acids?
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
How are fatty acids prepared for oxidation?
Fatty acids are prepared or “primed” with addition of CoA group by Acyl-CoA synthase
Transport of Fatty Acyl-CoA into the mitochondrion:
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
Beta oxidation of fatty acids in the mitochondrion:
1st reaction
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
Beta oxidation of fatty acids in the mitochondrion:
2nd and 3rd reaction
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
Beta oxidation of fatty acids in the mitochondrion:
Last reaction of the cycle
(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
Summary of Fatty acid Oxidation
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
What is the first step of synthesis of lipids?
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
Where does glycerol 3-phosphate come from?
Glycerol 3-phosphate is formed primarily by the reduction of dihydroxyacetone phosphate, an intermediate of the glycolysis pathway
What occurs during synthesis of triacylglycerol synthesis?
- ) The phosphatidate is hydrolyzed by a phosphatase (an enzyme that removes phosphate) to yield diacylglycerol (DAG)
- ) The DAG is acylated (adding of acyl group) to triacylglycerol by the enzyme diacylglycerol acyltransferase (DGAT)
