The patient was a young girl who had a history of severe abdominal pain and was taken to the local hospital at 5 a.m. in severe distress. Her blood was drawn, and it was observed that her plasma had a milky appearance with a triacylglycerol level greater than 2,000 mg/dl (normal range being 4–150 mg/dl). To address this issue, the patient was put on a diet that was extremely low in fat but included medium-chain triglycerides.

The most likely lipoprotein particles responsible for the milky appearance of the patient's plasma are chylomicrons. These particles contain a high concentration of triacylglycerols. Given that the patient arrived at the hospital at 5 a.m., several hours after her last meal, it suggests that she has difficulty in degrading these lipoprotein particles. The other lipoprotein particles such as intermediate-density lipoproteins, low-density lipoproteins, and high-density lipoproteins primarily consist of cholesteryl esters. If any of these particles were elevated, it would cause hypercholesterolemia. Very-low-density lipoproteins, on the other hand, do not cause the described milky appearance of plasma.

The most likely protein to be deficient in this patient is apolipoprotein C-II. The degradation of triacylglycerols in chylomicrons is facilitated by endothelial lipoprotein lipase (LPL), which requires apolipoprotein C-II as a coenzyme. Deficiency of LPL or apo C-II results in a decreased ability to degrade chylomicrons, which leads to their accumulation. The remnants of these chylomicrons are cleared by liver receptors with the help of apo E. Apolipoprotein A-I is involved in lecithin:cholesterol acyltransferase activity. Apolipoprotein B-48 is a structural protein found in chylomicrons. Cholesteryl ester transfer protein catalyzes the exchange of cholesteryl ester and triacylglycerol between high-density and very-low-density lipoproteins. Microsomal triglyceride transfer protein, on the other hand, is involved in the formation, not degradation, of chylomicrons and very-low-density lipoproteins.

If the individual had a deficiency in 17-α-hydroxylase instead of 21-α-hydroxylase, the results would be different. In classic 21-α-hydroxylase deficiency, mineralocorticoids (aldosterone) and glucocorticoids (cortisol) are virtually absent. This leads to a decrease in blood pressure and blood glucose levels since aldosterone increases blood pressure and cortisol increases blood glucose. Cortisol normally inhibits the release of adrenocorticotropic hormone (ACTH) by the pituitary through feedback mechanisms. In the absence of cortisol, there is an elevation in ACTH levels. The loss of 21-α-hydroxylase enzyme activity causes progesterone and pregnenolone to be diverted to androgen synthesis, resulting in an increase in androstenedione levels. If there was a deficiency in 17-α-hydroxylase, sex hormone synthesis would be decreased, while mineralocorticoid production would be increased, leading to hypertension.
A young girl with a history of severe abdominal pain was taken to her local hospital at 5 a.m. in severe distress. Blood was drawn, and the plasma appeared milky, with the triacylglycerol level >2,000 mg/dl (normal = 4–150 mg/dl). The patient was placed on a diet extremely limited in fat but supplemented with medium-chain triglycerides.
8.3. Which of the following lipoprotein particles are most likely responsible for the appearance of the patient’s plasma?
A. Chylomicrons
B. High-density lipoproteins
C. Intermediate-density lipoproteins
D. Low-density lipoproteins
E. Very-low-density lipoproteins
Correct answer = A. The milky appearance of her plasma was a result of triacylglycerol-rich chylomicrons. Because 5 a.m. is presumably several hours after her evening meal, the patient must have difficulty degrading these lipoprotein particles. Intermediate-, low-, and high-density lipoproteins contain primarily cholesteryl esters, and, if one or more of these particles was elevated, it would cause hypercholesterolemia. Very-low-density lipoproteins do not cause the described milky appearance of plasma.
8.4. Which one of the following proteins is most likely to be deficient in this patient?
A. Apolipoprotein A-I B. Apolipoprotein B-48
C. Apolipoprotein C-II
D. Cholesteryl ester transfer protein
E. Microsomal triglyceride transfer protein
Correct answer = C. The triacylglycerol (TAG) in chylomicrons is degraded by endothelial lipoprotein lipase (LPL), which requires apolipoprotein (apo) C-II as a coenzyme. Deficiency of LPL or apo C-II results in decreased ability to degrade chylomicrons to their remnants, which get cleared (via apo E) by liver receptors. Apo A-I is the coenzyme for lecithin:cholesterol acyltransferase; apo B-48 is the characteristic structural protein of chylomicrons; cholesteryl ester transfer protein catalyzes the cholesteryl ester–TAG exchange between high-density and very-low-density lipoproteins (VLDL); and microsomal triglyceride transfer protein is involved in the formation, not degradation, of chylomicrons (and VLDL).
8.5. Complete the table below for an individual with classic 21-α-hydroxylase deficiency relative to a normal individual.
How might the results be changed if this individual were deficient in 17-αhydroxylase, rather than 21-α-hydroxylase?
Classic 21-α-hydroxylase deficiency causes mineralocorticoids (aldosterone) and glucocorticoids (cortisol) to be virtually absent. Because aldosterone increases blood pressure, and cortisol increases blood glucose, their deficiencies result in a decrease in blood pressure and blood glucose, respectively. Cortisol normally feeds back to inhibit adrenocorticotropic hormone (ACTH) release by the pituitary, and, so, its absence results in an elevation in ACTH. The loss of 21-α-hydroxylase pushes progesterone and pregnenolonetoandrogensynthesisand,therefore,causesandrostenedionelevelstorise.With17-α-hydroxylasedeficiency,sexhormonesynthesiswouldbedecreased.Mineralocorticoidproductionwouldbeincreased,leadingtohypertension.
UNIT IV Nitrogen Metabolism Amino Acids: Nitrogen Disposal 19
For additional ancillary materials related to this chapter, please visit thePoint.
I. OVERVIEW