Question 1

The initial step toward the synthesis of triglycerides from free fatty acids and glycerol within hepatocytes requires which of the following enzymes?&#10;A) glycerol kinase&#10;B) glycerol-3-phosphate dehydrogenase&#10;C) glyceraldehyde-3-phosphate dehydrogenase&#10;D) lipoprotein lipase&#10;E) hormone-sensitive lipase

Accepted Answer

Glycerol kinase is the enzyme that catalyzes the phosphorylation of glycerol to form glycerol-3-phosphate, which is the initial step in the synthesis of triglycerides from free fatty acids and glycerol within hepatocytes.  The major building block for the synthesis of TGs, in tissues other than adipose tissue, is glycerol. The glycerol backbone of TG is activated by phosphorylation at the sn3 position by glycerol kinase.

Question 2

Defective ChREBP function would result in a reduction in the synthesis of triglycerides due to loss of the activation of the expression of which of the following genes? A) glycerol kinase B) glycerol-3-phosphate acyltransferase C) hepatic lipase D) phosphatidic acid phosphatase E) phospholipase A₂

Accepted Answer

ChREBP (Carbohydrate Response Element Binding Protein) is involved in the regulation of genes necessary for lipogenesis, including glycerol-3-phosphate acyltransferase, which is crucial for triglyceride synthesis.

Question 3

You are tending to an infant who was born just after only 28 weeks of gestation. The infant exhibits bluish coloration of the skin and has rapid, shallow breathing indicative of respiratory distress syndrome (RDS). RDS results in preterm infants due to the lack of which of the following phospholipid classes normally generated by lung alveolar cells?

A) cardiolipin
B) phosphatidylcholine
C) phosphatidylethanolamine
D) phosphatidylinositol
E) phosphatidylserine

phosphatidylcholine

Accepted Answer

Phosphatidylcholine, also known as lecithin, is a major component of pulmonary surfactant, which reduces surface tension in the alveoli and is often deficient in preterm infants, leading to respiratory distress syndrome.  Phosphatidylcholines are a class of phospholipid also called lecithins. The lecithin dipalmitoyl lecithin is a component of pulmonary surfactant. Pulmonary surfactant is a surface-active phospholipoprotein complex lung alveolar cell, which is critical to the prevention of atelectasis (lung collapse) at the end of expiration. Infants born prior to 30 weeks' gestation have a significantly decreased capacity to synthesize the surfactant and are thus highly susceptible to respiratory distress within minutes of birth.

Question 4

The normal signal response initiated by certain growth factor-receptor interactions is an increase in the activity of protein kinase C (PKC). The activity of PKC is controlled by both calcium ion and lipid, particularly diacylglycerols. Abnormal cells hat do not exhibit normal activation of PKC in response to addition of growth factor would most likely be lacking in the ability to synthesize which of the following class of phospholipid?

A) cardiolipin
B) phosphatidylcholine
C) phosphatidylethanolamine
D) phosphatidylinositol
E) phosphatidylserine

Accepted Answer

Phosphatidylinositol is a precursor for diacylglycerol, which is necessary for PKC activation. Phosphatidylinositols with phosphorylated inositol are termed polyphosphoinositides. The polyphosphoinositides are important intracellular transducers of signals emanating from the plasma membrane. One polyphosphoinositide (phosphatidylinositol 4,5-bisphosphate, PIP₂) is a critically important membrane phospholipid involved in the transmission of signals for cell growth and differentiation from outside the cell to inside. Numerous G-protein- coupled receptors activate phospholipase A2, which releases diacylglycerol (DAG) and inositol trisphosphate (IP₂) from PIP₂. The IP₂ binds to receptors on ER membranes resulting in the release of stored calcium into the cytosol.

Question 5

Hypersensitive individuals have IgE to specific antigens (eg, pollen, bee venom) on the surface of their leukocytes (monocytes, macrophages, basophils, eosinophils). When these individuals are challenged with antigen, the antigen-IgE complexes induce synthesis and release of which of the following physiologically potent lipids?

A) arachidonic acid
B) leukotriene B₄
C) platelet-activating factor
D) prostaglandin E₂
E) thromboxane A₂

Accepted Answer

Platelet-activating factor (PAF) is a potent lipid mediator that is synthesized and released by activated leukocytes. PAF is involved in a variety of inflammatory and allergic reactions, including anaphylaxis.

Question 6

Activation of phospholipase D (PLD) would be expected to result in an increased level of which of the following compounds?&#10;A) cardiolipin&#10;B) diacylglycerol&#10;C) dihydroxyacetone phosphate&#10;D) platelet-activating factor&#10;E) phosphatidic acid

Accepted Answer

Activation of phospholipase D (PLD) hydrolyzes phosphatidylcholine to produce phosphatidic acid and choline, leading to an increased level of phosphatidic acid.  Phospholipase D hydrolyzes the alcohol esterified to the phosphate of phospholipids. The products of the action of PLD are, therefore, phosphatidic acid and the original alcohol such as inositol of ethanolamine, for example.

Question 7

Studies on a cell line derived from a biopsy of a liver tumor demonstrate that these cells are unable to synthesize triglycerides. Which of the following enzymes is most likely defective, or missing, from these cells resulting in the loss of triglyceride synthesis?

A) glycerol kinase
B) glycerol-3-phosphate acyltransferase
C) glycerol-3-phosphate dehydrogenase
D) hepatic lipase
E) phosphatidic acid phosphatase

Accepted Answer

Hepatocytes utilize glycerol as the building block for the synthesis of triglycerides. The glycerol backbone is activated by phosphorylation at the C-3 position by glycerol kinase. Therefore, a loss of glycerol kinase activity in these cells would most likely explain the reduced capability to synthesize triglycerides.

Question 8

Phosphatidic acid, synthesized from glycerol 3-phosphate and 2 molecules of fatty acyl-CoA, is a key intermediate in the biosynthesis of which of the following?&#10;A) bile salts&#10;B) glycosphingolipids&#10;C) phospholipids&#10;D) prostaglandins&#10;E) steroid hormones

Accepted Answer

Phosphatidic acid is a precursor in the biosynthesis of phospholipids, which are essential components of cell membranes.  Phosphatidic acid serves as an intermediate in the synthesis of triglycerides and phospholipids. The fatty acids incorporated into triglycerides are activated to acyl-CoAs through the action of acylCoA synthetases. Two molecules of acyl-CoA are esterified to glycerol 3-phosphate to yield phosphatidic acid. The phosphate is then removed, by phosphatidic acid phosphatase (PAP1), to yield 1,2-diacylglycerol, the substrate for addition of the third fatty acid of a triglyceride. Phospholipids are synthesized by esterification of an alcohol to the phosphate of phosphatidic acid.

Question 9

In adipose tissue, synthesis of triglycerides from fatty acids derived from chylomicrons requires glycolysis for the synthesis of which of the following? A) acetyl-CoA B) citrate C) glycerol 3-phosphate D) NADP⁺ E) NADPH

Accepted Answer

Glycolysis provides dihydroxyacetone phosphate, which is reduced to glycerol 3-phosphate, a necessary backbone for triglyceride synthesis in adipose tissue.

Question 10

Platelet-activating factor (PAF) causes release of arachidonic acid from membrane lipids. Which of the following enzymes is most likely responsible for this effect?&#10;A) cyclooxygenase&#10;B) lipoprotein lipase&#10;C) lipoxygenase&#10;D) phospholipase A2&#10;E) thromboxane synthase

Accepted Answer

Phospholipase A2 is the enzyme responsible for releasing arachidonic acid from membrane phospholipids, which is a key step in the production of eicosanoids.  Arachidonic acid is found esterified to the sn2 position of the glycerol backbone of membrane phospholipids. Activation of membrane receptors, such as that which is activated by PAF, leads to activation of phospholipase A2, which hydrolyzes the ester bond at the sn2 position in phospholipids.

Deck 20: Lipids: Triglyceride and Phospholipid Synthesis