Clinical Correlates 4 Fatty Acids

Question 1

Total parenteral nutrition (TPN) is an __ form of nutrition containing essential fatty acids required in the diet. TPN is used in chronic illness, infection, trauma, burn injuries, postsurgery recovery, starvation, and kidney or liver failure. TPN avoids using the gastrointestinal tract.

Answer 1

intravenous

Question 2

In intestinal epithelial cells, triacylglycerol synthesis occurs by a different pathway than in other tissues. This triacylglycerol becomes a component of chylomicrons. Ultimately, the fatty acyl groups are stored in adipose triacylglycerols.

Answer 2

In liver and adipose tissue, glycerol 3-phosphate provides the glycerol moiety that reacts with two fatty acyl CoA molecules to form phosphatidic acid. The phosphate group is cleaved to form a diacylglycerol, which reacts with another fatty acyl CoA to form a triacylglycerol.

Question 3

Elevated triglyceride (triacylglycerol) > ___ can cause pancreatitis, an inflammation of the pancreas that causes severe abdominal pain.

Answer 3

1000 mg/dL

Question 4

Chylous ascites is the extravasation of milky chyle (lymph) with a triglyceride (triacylglycerol) level of more than ___ into the peritoneal cavity of the abdomen. (Fluid collection in the peritoneum is ascites.) Chylous ascites occurs in abdominal surgery, abdominal trauma, and cancers such as ___, in which the lymphatic system is obstructed.

Answer 4

200 mg/dL

lymphomas

Question 5

______ is a deficiency of the plasma membrane carnitine transporter, leading to urinary wasting of carnitine. Subsequent depletion of intracellular carnitine impairs transport of____ ___ into mitochondria, limiting fatty acid availability for oxidation and energy production.

Answer 5

Primary carnitine deficiency

long-chain fatty acids

Question 6

Cytosolic fatty acyl CoA reacts with carnitine in the outer mitochondrial membrane, forming fatty acyl carnitine via carnitine acyl transferase I (CAT I), also called carnitine palmitoyl transferase I (CPT I).

Answer 6

Fatty acyl carnitine passes to the inner membrane, where it reacts with carnitine acyl transferase II (CAT II) to reform fatty acyl CoA, which enters the mitochondrial matrix.

Question 7

CAT I, which catalyzes the transfer of acyl groups from coenzyme A to carnitine, is inhibited by malonyl CoA, an intermediate in fatty acid synthesis.

Answer 7

Therefore, when fatty acids are synthesized in the cytosol, malonyl CoA inhibits their transport into mitochondria, preventing a futile cycle (synthesis followed by immediate degradation).

Question 8

___ ___ results in intermittent ataxia, oculomotor palsy (cranial nerve [CN] III), hypotonia, mental confusion, and disturbance of consciousness.

Answer 8

CAT I deficiency

Question 9

Inside the mitochondrion, fatty acyl CoA undergoes ?

Answer 9

b-oxidation

Question 10

______ (MCAD) deficiency is a deficiency of one of the acyl CoA dehydrogenases, which oxidizes fatty acids between 6 and 10 carbons long. The defect is manifested when serum glucose levels are low (hypoglycemia) because of fasting, infection, or increased amount of time between feedings. Fatty acids cannot be fully oxidized as an alternate form of energy in individuals with this disorder.

Answer 10

Medium-chain acyl CoA dehydrogenase

Question 11

___ ___ is a peroxisomal disorder resulting in accumulation of very-long-chain fatty acids because the peroxisome is not properly formed. Clinical Manifestations include congenital craniofacial dysmorphism, psychomotor retardation, and seizures. Death results in the first year of life.

Answer 11

Zellweger syndrome

Question 12

____ is a rare metabolic disorder. Very-long-chain fatty acids accumulate in the brain (causing demyelination) and in the adrenal cortex (causing degeneration) because of an inability to transport very-long-chain fatty acids into peroxisomes. Clinical manifestations include psychomotor retardation and seizures.

Answer 12

Adrenoleukodystrophy

Question 13

1. A 41-year-old woman presents with severe, sharp epigastric abdominal pain that radiates to her back and with nausea and vomiting. Laboratory results indicate a serum triglyceride level of 5000 mg/dL. She is diagnosed with pancreatitis, in part owing to her elevated serum triacylglycerol levels. To form triacylglycerol from diacylglycerol, which of the following compounds is also required?
(A) Glycerol
(B) Glycerol 3-phosphate
(C) Fatty acyl CoA
(D) Acetyl CoA
(E) Malonyl CoA

Answer 13

C. Triacylglycerol is formed when a diacylglycerol reacts with a fatty acyl CoA.
Glycerol and glycerol 3-phosphate form the backbone of the triacylglycerol. Acetyl CoA and malonyl CoA are involved in fatty acid synthesis, and not directly in triacylglycerol synthesis.

Question 14

2. An 18-year-old woman presents with xanthomas on her eyelids and is found to have a rare genetic deficiency of lipoprotein lipase. She is diagnosed with type I hyperlipidemia. In this disorder, chylomicrons are abnormally elevated in the serum. In which cell or tissue does triacylglycerol packaging into chylomicrons occur?
(A) Intestinal epithelial cell
(B) Liver cell
(C) Muscle cell
(D) Heart cell
(E) Adipose cell

Answer 14

A. Intestinal epithelial cells are the site of chylomicron formation. Dietary triacylglycerols are bound to apoproteins and other lipids to form the chylomicrons. In the liver, triacylglycerols are incorporated into VLDLs, which enter the blood. Triacylglycerols are stored in adipose tissue. The muscle, heart, and adipose cells do not package triacylglycerol into particles for export into the circulation.

Question 15

3. A 2-week-old child underwent complex congenital heart malformation repair. The cardiothoracic surgeon accompanies the patient back from the operating room and tells the pediatric intensive care unit staff that the ASD (atrial septal defect) and VSD (ventricular septal defect) were successfully repaired. However, the thoracic duct was accidentally cut, and daily echocardiograms will be needed to evaluate for cor pulmonale (alterations in the right ventricle of the heart). Which one of the following statements is true concerning fat metabolism in this patient?
   (A) The thoracic duct carries a substantial volume of lymph and triglycerides from the enteric circulation to the venous system.
   (B) Triacylglycerol is primarily stored in the liver.
   (C) In the intestinal cell, glucose is converted to triacylglycerol by phosphatidic acid.
   (D) In adipose cells, triacylglycerol is converted to VLDL.
   (E) Somatostatin has no role in the treatment of chylothorax in children.

Answer 15

A. The thoracic duct carries lymph and triglyceride from the enteric circulation to the venous system. Chylothorax is the accumulation of chylous fluid from a compromised thoracic duct. Nontraumatic causes (e.g., malignant erosion) or traumatic causes (e.g., blunt trauma, cardiothoracic surgery) result in the slow accumulation of a milky fluid rich in triglycerides in the chest cavity. Treatment is medical (somatostatin in children) and surgical (percutaneous drainage or thoracostomy tube drainage). Triglyceride is primarily stored in the adipose cells. Intestinal cells do not produce triglyceride from glucose; these cells pass glucose directly into the circulation. VLDL is produced by the liver, not adipose tissue.

Question 16

4. An 18-year-old obese woman maintains a sedentary lifestyle and eats a high-fat, highcarbohydrate diet. Maintenance of this diet and lifestyle has led to lipogenesis and obesity. Which of the following statements correctly describes an aspect of lipogenesis?
   (A) The primary source of carbons for fatty acid synthesis is glycerol.
   (B) Fatty acids are synthesized from acetyl CoA in the mitochondria.
   (C) Fatty acid synthesis and esterification to glycerol to form triacylglycerols occurs primarily in muscle cells.
   (D) The fatty acyl chain on the fatty acid synthase complex is elongated two carbons at a time.
   (E) NADP+, which is important for fatty acid synthesis, is produced by the pentose phosphate pathway.

Answer 16

D. The primary source of carbons for fatty acid synthesis is dietary carbohydrate. Fatty acids are synthesized from acetyl CoA in the hepatocyte cytosol, and esterification to glycerol to form triacylglycerols also occurs primarily in the liver. The fatty acyl chain on the fatty acid synthase complex is elongated two carbons at a time. With each two-carbon addition to the elongating chain, the b-keto group is reduced in a reaction that requires NADPH. NADPH is a reducing equivalent produced by the pentose phosphate pathway and the malic enzyme. NADP+ is a product of fatty acid biosynthesis, not a substrate.

Question 17

5. A 45-year-old man presents with multiple gunshot wounds to the abdomen requiring an emergent  laparotomy, jejunectomy, and colectomy. After surgery, he is placed on intravenous nutrition (i.e., TPN). Which of the following compounds should be a component of TPN?
(A) Palmitate
(B) Linoleate
(C) Phosphatidic acid
(D) Glycerol
(E) Glucose

Answer 17

B. Linoleate and a-linolenate are the essential fatty acids required in the human diet. Palmitate (C16:0) is synthesized by the fatty acid synthase complex. Phosphatidic acid is an intermediate in triacylglycerol synthesis, which is formed using glycerol as a precursor in the liver and using glucose as a precursor in adipose tissue. It can be synthesized without the need for an essential fatty acid.

Question 18

6. A 16-year-old girl presents with extreme
   slenderness. Her body weight is 35% below
   expected. She feels as though she is obese and
   severely restricts her food intake. She is diagnosed with anorexia nervosa. In this patient, breakdown of fatty acids is required to provide energy. Before being oxidized, fatty acids are activated in the cytosol to form which of the following?
   (A) ATP
   (B) CoA
   (C) Fatty acyl CoA
   (D) Carnitine
   (E) Malonyl CoA

Answer 18

C. Long-chain fatty acids are activated, in a reaction requiring ATP and CoA, to a fatty acyl CoA. Carnitine reacts with fatty acyl CoA, forming fatty acyl carnitine, in order to transport the fatty acid across the mitochondrial membrane. Malonyl CoA is an intermediate in fatty acid synthesis.

Question 19

7. After surgical resection of part of her small intestine, a 40-year-old woman presents with chronic foul-smelling diarrhea and weight loss. She is diagnosed with short bowel syndrome. In this syndrome, fat cannot be properly absorbed, so long-chain fatty acids are mobilized from adipose tissue to generate energy for cell survival. The initiating substrate for fatty acid oxidation is which of the following?
(A) Long-chain fatty acid
(B) Fatty acyl carnitine
(C) Fatty acyl CoA
(D) b-Hydroxyacyl CoA
(E) Acetyl CoA

Answer 19

C. Fatty acyl CoA undergoes b-oxidation in a spiral involving four steps. Longchain fatty acids are released from adipose cells and must be activated and transported into mitochondria for oxidation. Fatty acyl CoA reacts with carnitine, forming fatty acyl carnitine, which crosses the inner mitochondrial membrane. The acyl group is then transferred back to CoA, forming fatty acyl CoA in the mitochondrial matrix. Subsequent reactions convert the fatty acyl CoA to trans2 fatty enoyl CoA, b-hydroxy acyl CoA, and keto acyl CoA. The end product of fatty acid oxidation is acetyl CoA, which is oxidized via the TCA cycle and oxidative phosphorylation to produce carbon dioxide, water, and ATP.

Question 20

8. An infant is born with a high forehead, abnormal eye folds, and deformed ear lobes and shows little muscle tone and movement. After multiple tests, he is diagnosed with Zellweger syndrome, a disorder caused by peroxisome malformation. What type of fatty acid would you expect to accumulate in patients with Zellweger syndrome?
(A) Short-chain fatty acids
(B) Acetyl CoA
(C) Dicarboxylic acids
(D) Long-chain fatty acids
(E) Very-long-chain fatty acids

Answer 20

E. Very-long-chain fatty acids are initially oxidized in peroxisomes, generating hydrogen peroxide, NADH, and acetyl CoA. Once the fatty acids have been shortened to about 8 to 10 carbons in length, they are transferred to the mitochondria to finish their oxidation via traditional b-oxidation. Thus, very-long-chain fatty acids will accumulate with this peroxisomal disorder. Short-chain and long-chain fatty acids are oxidized within the mitochondria via b-oxidation. Acetyl CoA will not accumulate with a peroxisomal disorder because it will also be oxidized in the mitochondria. Dicarboxylic acids accumulate when there is a defect in mitochondrial b-oxidation, and o-oxidation begins to play a larger role in generating energy.

Question 21

9. A 4-month-old infant presents with a seizure. His mother reports that her infant has been irritable and lethargic over the past several days. The infant is found to be profoundly hypoglycemic and have low ketones. Short-chain dicarboxylic acids are found to be elevated in the serum. The most likely enzyme deficiency is which of the following?
(A) Medium-chain acyl CoA dehydrogenase
(MCAD)
(B) Carnitine acyltransferase I
(C) Hormone-sensitive lipase
(D) Pyruvate carboxylase
(E) Fatty acyl CoA synthetase

Answer 21

A. The infant has MCAD deficiency. The child can only partially oxidize fatty acids (to the 6- to 10-carbon stage), leading to reduced energy generation and low acetyl CoA levels. The low acetyl CoA reduces gluconeogenesis because pyruvate carboxylase cannot be fully activated. The reduced energy also contributes to the reduced levels of gluconeogenesis because that pathway requires energy to proceed. The dicarboxylic acids result from o-oxidation of the medium-chain acyl CoAs, to try and generate more energy. Defects in CAT I or hormonesensitive lipase would result in a complete lack of fatty acid oxidation, and the dicarboxylic acids
would not be observed. A defect in pyruvate carboxylase, although negatively affecting gluconeogenesis,
would not affect fatty acid oxidation.

Question 22

10. A 12-year-old Jamaican boy presents with intractable vomiting, abdominal pain, and lethargy and is profoundly hypoglycemic. His symptoms are caused by Jamaican vomiting syndrome, a sickness caused by ingestion of hypoglycin, which is present in unripe ackee fruit. Hypoglycin is metabolized to a form of nonmetabolizable carnitine, which interferes with normal fatty acid oxidation. What is the primary role of carnitine?
    (A) Activates long-chain fatty acids in the
    cytosol
    (B) Transport of acyl groups across the inner
    mitochondrial membrane
    (C) Is converted to enoyl CoA
    (D) Is converted to b-hydroxyacyl CoA
    (E) Is involved in breakdown of even-chain,
    but not odd-chain, fatty acids

Answer 22

B. In the outer mitochondrial membrane, carnitine reacts with fatty acyl CoA to form fatty acyl carnitine, which can then pass to the inner mitochondrial membrane. Therefore, carnitine is important for the transport of fatty acyl CoA from the cytosol to the mitochondria and allow for b-oxidation to occur. Carnitine is not involved in activation of fatty acids or
b-oxidation itself (which eliminates answer choices A, C, D, and E). As a note of interest, hypoglycin leads to inhibition of gluconeogenesis (due to a lack of fatty acid oxidation, leading to low ATP and acetyl CoA levels). Profound hypoglycemia results, which is how hypoglycin was
named.