Clinical Correlates 6 Ketones & Lipid Derivatives Flashcards Preview

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Flashcards in Clinical Correlates 6 Ketones & Lipid Derivatives Deck (16):
1

Type 1 diabetes mellitus is due to a deficiency of insulin, which is caused by autoimmune destruction of insulin-producing cells in the pancreas. Insulin is required for glucose to be used by cells. Deficiency of insulin leads to a state known as diabetic ____, which manifests as a severely elevated serum ___ level, increased ___ synthesis, and formation of ___ due to decarboxylation of acetoacetate.

ketoacidosis
glucose
ketone body
acetone

2

Respiratory distress syndrome (RDS) of the newborn occurs in premature infants due to a deficiency of ____ in the lungs, which leads to a decrease
in lung compliance. Dipalmitoyl phosphatidylcholine (DPPC, also called lecithin), is the primary phospholipid in surfactant, which lowers ____ at the alveolar air–fluid interface. Surfactant is normally produced at gestational week __.

surfactant
surface tension
30

3

Steroids, such as _____ ___, are often prescribed for inflammatory or autoimmune diseases, such as rheumatoid arthritis, a debilitating inflammatory joint disease.

cortisone and prednisone

4

Aspirin has been shown to be ____ in myocardial infarction. Although PGI2 is also inhibited, the cardioprotective effect is mediated by inhibiting __

cardioprotective
TXA2.

5

____ causes severe breathing difficulty due to hyperreactivity and narrowing of the airways. Because leukotrienes cause bronchoconstriction,____ ___ can be prescribed as a treatment.

Asthma
leukotriene-receptor antagonists

6

3-b-Hydroxysteroid dehydrogenase deficiency is a disease resulting in decreased production of ___ ___ ___ (3-bhydroxysteroid dehydrogenase is required for production of all three types of steroids). Male infants manifest with ambiguous genitalia (owing to lack of androgens), and both males and females show___ ___ (owing to lack of aldosterone).

aldosterone, cortisol, and androgens
salt wasting

7

17-a-hydroxylase deficiency is a disease resulting in decreased production of ___ ___ but increased production of___. Male and female teenagers are usually diagnosed during puberty with lack of secondary sexual characteristics. Increased aldosterone can cause excessive ____.

cortisol and androgens
aldosterone
salt absorption

8

1. A 12-year-old boy presents with fatigue, polydipsia, polyuria, and polyphagia. A fingerstick glucose measurement shows a glucose level of 350mg/dL in his serum. He is diagnosed with type 1 diabetes mellitus, a disease characterized by a deficiency of insulin.Which one of the following ismost likely occurring in this patient?
(A) Increased fatty acid synthesis from glucose in liver
(B) Decreased conversion of fatty acids to ketone bodies
(C) Increased stores of triacylglycerol in adipose tissue
(D) Increased production of acetone
(E) Chronic pancreatitis

D. A decreased insulin-to-glucagon ratio leads to a decrease in fatty acid synthesis and an increase in adipose triacylglycerol degradation, leading to fatty acid release into the circulation. The liver takes up the fatty acids, and within the mitochondria, fatty acids undergo b-oxidization. As acetyl CoA accumulates, the ketone bodies, acetoacetate and b-hydroxybutyrate, are formed and are released into the circulation. These ketone bodies are used to fuel the heart, brain, and muscle. Nonenzymatic decarboxylation of acetoacetate forms acetone, which can be smelled by some providers on the breath of patients in diabetic ketoacidosis. Because triglycerides are degraded under these conditions, there is not an increase in triglyceride storage. Pancreatitis
does not result from an inability to produce insulin.

9

2. A 58-year-old woman is undergoing a myocardial infarct and is given 162 mg of aspirin, owing to the cardioprotective effects of aspirin during such an incident. Aspirin is a nonsteroidal anti-inflammatory drug that inhibits cyclooxygenase. Cyclooxygenase is required for which one of the following conversions?
(A) Thromboxanes from arachidonic acid
(B) Leukotrienes from arachidonic acid
(C) Phospholipids from arachidonic acid
(D) Arachidonic acid from linoleic acid
(E) HPETEs and subsequently hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid

A. Prostaglandins, prostacyclins, and thromboxanes are synthesized from arachidonic acid by the action of cyclooxygenase. Inhibiting cyclooxygenase decreases the synthesis of prostaglandins. Leukotriene synthesis requires the enzyme lipoxygenase. Phospholipid synthesis does not require any oxygenase reaction. The conversion of linoleic acid to arachidonic acid involves fatty acid elongation and desaturation reactions, but not the participation of cyclooxygenase. HPETE and HETE synthesis is through the leukotriene pathway, or through a cytochrome
P-450–mediated pathway.

10

3. The cardioprotective effects of aspirin occur due to the inhibition of the synthesis of which one of the following?
(A) PGF2a
(B) PGE2
(C) TXA2
(D) PGA2
(E) PGI2

C. Even though inhibition of cyclooxygenase leads to a decrease in synthesis of all the answers listed (PGF2a, PGE2, TXA2, PGA2, and PGI2), it is the inhibition of thromboxane A2 that is cardioprotective. TXA2 is a potent vasoconstrictor and a stimulator of platelet aggregation. The stimulation of platelet aggregation initiates thrombus formation at sites of vascular injury as
well as in the vicinity of a ruptured atherosclerotic plaque in the lumen of vessels. Inhibition of TXA2 synthesis reduces the risk for thrombus formation and occlusion of a vascular vessel.

11

4. A 40-year-old woman has rheumatoid arthritis, a crippling disease causing severe pain and deformation in the joints of the fingers. She is prescribed prednisone, a steroid that exerts its beneficial effects through anti- inflammatory pathways. What is the mechanism of steroidal anti-inflammatory agents?
(A) Prevent conversion of arachidonic acid to epoxides
(B) Inhibit phospholipase A2
(C) Promote activation of prostacyclins
(D) Degrade thromboxanes
(E) Promote leukotriene formation from HPETEs

B. Steroids such as cortisone and prednisone inhibit phospholipase A2, which cleaves arachidonic acid from membrane phospholipids. In the absence of free arachidonic acid, the formation of prostaglandins and leukotrienes is reduced. Because these molecules are mediating the ‘‘pain’’ response, a reduction in their synthesis results in a feeling of less pain for the affected individual. Steroids do not prevent the conversion of arachidonic acid to epoxides, activate prostaglandins, degrade thromboxane, or stimulate leukotriene production.

12

5. An infant is born prematurely at 28 weeks and increasingly has significant difficulty breathing, taking rapid breaths with intercostal retractions. The child soon becomes cyanotic. He is diagnosed with respiratory distress syndrome due to a deficiency of surfactant. Which of the following is the phospholipid in highest
concentration in surfactant?
(A) Dipalmitoyl phosphatidylcholine
(B) Dipalmitoyl phosphatidylethanolamine
(C) Dipalmitoyl phosphatidylglycerol
(D) Dipalmitoyl phosphatidylinositol
(E) Dipalmitoyl phosphatidylserine

A. Dipalmitoyl phosphatidylcholine (DPPC), also called lecithin, is the major phospholipid in surfactant. Surfactant is a protein and lipid mixture that is responsible for lowering surface tension at the alveolar air–fluid interface. DPPC contains a glycerol backbone, palmitic acid, esterified at positions 1 and 2, and phosphocholine esterified at position 3. The other phospholipids suggested as answers are present in nonappreciable levels in surfactant.

13

6. An 11-year-old Ashkenazi Jewish girl presents with an enlarged liver and spleen, low white and red blood cell counts, bone pain, and bruising. She is diagnosed with Gaucher disease, a lysosomal storage disease. Which of the following compounds is accumulating in her lysosomes?
(A) Galactocerebroside
(B) Ceramide
(C) Glucocerebroside
(D) Sphingosine
(E) GM1

C. Patients with Gaucher disease have a deficiency of b-glucocerebrosidase, resulting in glucocerebroside accumulation in the lysosomes of cells of the liver, spleen, and bone marrow. Galactocerebroside accumulates in Krabbe disease. Ceramide accumulation is associated
with Farber disease. Sphingosine accumulation is associated with Niemann-Pick disease. GM1 accumulation is associated with generalized gangliosidosis.

14

7. A 4-month-old infant presents with muscular weakness that is progressing to paralysis. Examination of the back of the eye shows a cherryred spot on the macula. An abnormally low level of hexosaminidase A is present, causing deposition of certain gangliosides in neurons. The accumulating material in this disorder is which of the following?
(A) GM1
(B) GM2
(C) GM3
(D) GD3
(E) GT3

B. This patient has either Tay-Sachs or Sandoff disease. Patients with these diseases have a deficiency of hexosaminidase A (Tay-Sachs), or hexosaminidase A and B (Sandhoff) activity, resulting in the buildup of GM2 in neurons, which can result in neurodegeneration and early death. Hexosaminidase A (which is composed of proteins encoded by the HexA and HexB genes) removes N-acetylgalactosamine from GM2, to form GM3. TheM series of gangliosides contain 1 sialic acid residue; the D series contain 2 sialic acid residues, and the T series contain 3 sialic acid residues.

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8. A male infant with 3-b-hydroxylase deficiency is born with ambiguous genitalia and severe salt wasting from lack of androgens and aldosterone, respectively. Testosterone, a major androgen, is produced by which of the following reactions?
(A) Oxidation of the A ring of pregnenolone
(B) Removal of the side chain of the D ring of progesterone
(C) Aromatization of the A ring of estradiol
(D) Cleavage of the side chain of progesterone
(E) Oxidation of aldosterone

B. 3-b-Hydroxylase deficiency is a disease resulting in decreased production of aldosterone, cortisol, and androgens (3-b-hydroxylase is required for production of all three types of steroids). Male infants manifest with ambiguous genitalia (owing to lack of androgens and testosterone), and both males and females show salt wasting (owing to lack of aldosterone). Testosterone is produced only by the removal of the side chain of the D ring of progesterone.

16

9. A 2-year-old girl is failing to meet age-appropriate milestones, including a progressive difficulty in walking. An abnormally low level of arylsulfatase A is found in her cells, causing accumulation of sulfated glycolipids in neurons. Unfortunately, she dies 5 years later. Which one of the following is the most likely diagnosis for this disorder?
(A) Fabry disease
(B) Gaucher disease
(C) Niemann-Pick disease
(D) Tay-Sachs disease
(E) Metachromatic leukodystrophy

E. Metachromatic leukodystrophy is due to a deficiency in arylsulfatase A, a lysosomal enzyme that degrades sulfated glycolipids. These sulfatide compounds accumulate in neural tissue, causing demyelination of central nervous system and peripheral nerves, with resultant loss of cognitive and motor functions. Fabry disease is a result of a deficiency in a-galactosidase A; Niemann-Pick is a result of a deficiency in sphingomyelinase; Gaucher disease is a result of a deficiency in glucocerebrosidase; and Tay-Sachs is a result of a deficiency in hexosaminidase A.