Module 10 - Lipid Synthesis Flashcards
Anabolic Steroids
Steroid molecules that are structurally related to and have similar effects as testosterone except that their anabolic activity is enhanced compared to their androgenic activity.
Lipoproteins
A group of soluble protein-lipid complexes that transport lipids in the blood
Statins
A class of drugs prescribed to lower cholesterol levels in the blood. They are HMG-CoA reductase competitive inhibitors.
Compare and contrast triacylglycerol and phospholipids
both have a glycerol backbone
in triacylglycerol, three fatty acids are linked to each of the three carbon atoms of glycerol
In phospholipids, there are two fatty acids linked to carbons 1 and 2 of glycerol, while a phosphate group and one of several different head groups are linked to carbon 3.
Where does triacylglycerol synthesis occur?
significant triacylglycerol synthesis only occurs in liver and adipose tissue
Where does phospholipid synthesis occur?
phospholipid synthesis occurs in all cells since they are major components of membranes
What is the common precursor for both triacylglycerol and phospholipids?
Glycerol-3-P is a common precursor for both classes of lipids
it can be derived either from glycerol released from adipose tissue when triacylglycerol is degraded (in liver only), or from the conversion of dihydroxyacetone phosphate (in liver and other tissues)
a molecule called phosphatidate is the precursor for both triacylglycerol and phospholipids
How is phosphatidate synthesized from glycerol-3-P?
It consists of two consecutive additions of a fatty acid (using an acyl-CoA derivative) to carbon 1 and then to carbon 2, via ester linkages.
The fatty acid linked to carbon 1 is usually a saturated fatty acid, while an unsaturated fatty acid is usually linked to carbon 2.
Carbon 3 has the phosphate group attached to it, which will facilitate the addition of different head groups to form different phospholipids
How is triacylglycerol synthesized from phosphatidate?
two-step process that is catalyzed by a triacylglycerol synthetase complex that is located on the ER membrane
In the first step, the phosphate group is cleaved off to form diacylglycerol.
In the second step the third fatty acid is linked to carbon 3 to form triacylglycerol.
Under normal conditions what happens to the triacylglyceride that is synthesized?
Under normal conditions, most of the triacylglycerol that is synthesized in liver is transported to either the muscle to be used as fuel or to adipose tissue where it is stored for future energy needs.
What are some of the common phospholipids?
There are several common membrane phospholipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol.
They have very similar structures and differ only in the head group (shown in red in Figure 10-5) attached to the phosphate group on carbon 3 of the glycerol backbone.
Phospholipids are _________________ molecules
amphiphilic
The have a very non-polar region due to the two fatty acid chains and a highly polar head group.
Where does phospholipid synthesis take place?
Phospholipid synthesis takes place in the endoplasmic reticulum
What is the precursor to phospholipid synthesis?
uses phosphatidate as a precursor to which an alcohol is linked (ethanolamine, choline, or serine)
How does the first part of phospholipid synthesis take place using an activated diacylglycerol?
(primarily in yeast and bacteria)
Diacylglycerol is activated by linking a CDP molecule to it.
In this reaction, phosphatidate reacts with CTP to form CDP-diacylglycerol.
The pyrophosphate (PPi) released is quickly hydrolyzed in the cell to two Pi.
the energy released from this hydrolysis drives this reaction strongly forward.
How does the second part of phospholipid synthesis take place using an activated diacylglycerol?
(primarily in yeast and bacteria)
CDP-diacylglycerol reacts with an alcohol such as choline to form the phospholipid with the release of CMP
How does phospholipid synthesis take place in mammals?
In the case of mammals, rather than diacylglycerol being activated, the alcohol is activated by linking it to CDP.
Example:
Note that ethanolamine rather than diacylglycerol is linked to CDP, and that diacylglycerol reacts with CDP-ethanolamine.
What is the most abundant phospholipid in animals?
Phosphatidylcholine is the most abundant phospholipid in animals and makes up 50% of membrane mass.
If phosphatidylcholine is the most abundant phospholipid in animals what happens if dietary choline available is insufficient?
the liver possesses an alternative route for the synthesis of phosphatidylcholine
In this reaction, phosphatidylcholine is synthesized from phosphatidylethanolamine by the enzyme phosphatidylethanolamine methyltransferase
The amino group of ethanolamine is methylated three times using S-adenosylmethionine (SAM) as the methyl donor
Why is cholesterol an important molecule?
It is a critical component of cell membranes that ensures it has proper fluidity.
It is also the precursor for: steroid hormones such as estrogen, progesterone, testosterone, and cortisol; bile salts, which aid in digestion; and vitamin D
Where does the synthesis of cholesterol occur?
our bodies have a pathway for its synthesis that occurs in all cells but especially in the liver
What is the precursor for the synthesis of cholesterol?
The precursor for its synthesis is acetyl CoA;
in fact, all 27 carbons in cholesterol are derived from acetyl CoA.
Where in the cell does the synthesis of cholesterol take place? And what are its characteristics?
occurs partly in the cytosol (2 stages) and partly in the ER (2 stages).
Note that it has four fused rings, a long hydrocarbon tail (carbons 20-27), a hydroxyl group on carbon 3, and a double bond between carbons 5 and 6.
It is highly non-polar and insoluble in water.
The first stage of cholesterol synthesis in the cytosol.
the first step is regulated
the synthesis of mevalonate from three acetyl CoA molecules
two molecules of acetyl CoA condense to form acetoacetyl CoA in the first step, and then a third acetyl CoA is condensed to form form hydroxymethylglutaryl-CoA (HMG-CoA).
This molecule is then reduced, using NADPH, to mevalonate by the enzyme HMG-CoA reductase.
