Vitamins and Minerals
After metabolic conversion in the body, coenzyme forms of folate and vitamin B12 are both involved in methylation of which of the following? A. homocysteine B. norepinephrine C. pyridine D. serotonin E. uridylic acid
Answer A: Both folic and cobalamin (B12) are involved in the function of methionine synthase. In the direction of methionine synthesis, the enzyme utilizes the methyl-group from N5-methyl-THF in the methylation of homocysteine. During this reaction, the methyl group is initially transferred to hydroxycobalamin-generating methylcobalamin.
You are examining a 27-year-old pregnant woman who is at 32 weeks' gestation. Blood work indicates she is suffering from macrocytic anemia. Her diet consists mainly of starchy foods with little meat and green vegetables. Which of the following vitamins is most likely deficient in this woman? A. folate B. vitamin B1 C. vitamin B2 D. vitamin B6 E. vitamin C
Answer A: Folate deficiency results in complications nearly identical to those of vitamin B12 deficiency. The most pronounced effect of folate deficiency on cellular processes is upon DNA synthesis. This is due to an impairment in dTMP synthesis, in particular in hematopoietic cells. The inability to synthesize DNA during erythrocyte maturation leads to abnormally large (macrocytic) erythrocytes and anemia.
Although α-lipoic acid is not truly a vitamin, it is an essential cofactor for several important enzymes. An inability to maintain adequate levels of this lipid-derived molecule would result in which of the following consequences? A. decreased insulin sensitivity B. decreased production of reactive oxygen species, ROS C. increased energy generation from carbohydrates D. increased hepatic production of triglycerides E. loss of the ability to clot blood
Answer A: Lipoic acid (LA) is an essential cofactor for the E2 component of α-ketoacid dehydrogenase complexes, exclusively located in mitochondria. These include the PDH, α-ketoglutarate dehydrogenase (KGDH), and branched chain α-ketoacid dehydrogenase (BCKDH) complexes. Extensive evidence suggests that LA may have therapeutic usefulness in lowering blood glucose levels in diabetic conditions and that the intracellular redox status plays a role in the modulation of insulin resistance. Lipoic acid has been shown to stimulate glucose uptake by affecting components of the insulin-signaling pathway.
Which of the following is associated with increased glucose uptake due to its ability to prevent phosphorylation of downstream effectors of the insulin-signaling cascade? A. α-lipoic acid B. vitamin A C. vitamin D D. vitamin E E. vitamin K
Answer A: Lipoic acid (LA) is an essential cofactor for the E2 component of α-ketoacid dehydrogenase complexes, exclusively located in mitochondria. These include the PDH, α-ketoglutarate dehydrogenase (KGDH), and branched chain α-ketoacid dehydrogenase (BCKDH) complexes. Extensive evidence suggests that LA may have therapeutic usefulness in lowering blood glucose levels in diabetic conditions and that the intracellular redox status plays a role in the modulation of insulin resistance. Lipoic acid has been shown to stimulate glucose uptake by affecting components of the insulin-signaling pathway.
A 29-year-old female has just become pregnant and is at the doctor's office for her first pre-natal exam. This is the first time this patient has been seen by the ob-gyn. In reviewing the patients medical records the physician discovers that the woman takes Dilantin (phenytoin) to control her epileptic seizures. The physician recommends that the woman stop the Dilantin and switch to Carbatrol (carbamazepine). If the woman refuses to comply with the change in seizure medication which of the following is most likely to be defective in her newborn resulting in potentially fatal bleeding episodes? A. γ-carboxylation of glutamate B. hydroxylation of lysine C. methylation of homocysteine D. oxidation of lysine E. synthesis of heme
Answer A: The hydantoin class (includes phenytoin) of anti-seizure medications interfere with the activity of vitamin K. Loss of vitamin K, as a co-factor, leads to reduced hepatic γ-carboxylation of glutamate residues in the coagulation factors II, VII, IX, X and also protein C and protein S. The net effect is defective, potentially fatal, bleeding disorder in a neonate.
A deficiency of vitamin B12 in humans results in anemia primarily because it is which of the following? A. a cofactor in the biosynthesis of purine nucleotides required for the synthesis of DNA B. involved in the conversion of N5-methyl-THF to THF C. necessary for the absorption of folic acid from the gut D. required for the conversion of cystathionine to cysteine E. utilized as a cofactor in synthesis of thymidine nucleotides
Answer B: Pernicious anemia is a megaloblastic anemia resulting from vitamin B12 deficiency that develops as a result of a lack of intrinsic factor in the stomach, leading to malabsorption of the vitamin. The anemia results from impaired DNA synthesis due to a block in purine and thymidine nucleotide biosynthesis. The block in nucleotide biosynthesis is a consequence of the effect of vitamin B12 on folate metabolism. When vitamin B12 is deficient, essentially all of the folate becomes trapped as the N5-methyl-THF derivative as a result of the loss of functional methionine synthase. This trapping prevents the synthesis of other THF derivatives required for the purine and thymidine nucleotide biosynthesis pathways.
A 23-year-old man has been consuming large quantities of raw egg whites as part of his current body-building routine. He has developed a rash and severe muscle pain. Blood work indicates he has anemia. His diet prevents intestinal absorption of a vitamin leading to inhibition in the synthesis of which of the following? A. DNA B. fatty acid C. glycogen D. protein E. RNA
Answer B: The avidin in egg whites complexes with biotin preventing its absorption from the intestines. Biotin is a cofactor for enzymes involved in carboxylation reactions. Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme of de novo fatty acid synthesis. Therefore, a deficiency in biotin absorption from the gut would be expected to have a negative effect on fatty acid synthesis.
A 45-year-old man is brought to the ER by his wife because he has exhibited confusion for the past few days. The attending physician asks him to follow his pen with his eyes. He notes that on extreme lateral motion his eyes exhibit an involuntary rhythmic movement toward the midline and then back to lateral gaze. The patient is unable to do finger-to-nose or heel-to-shin movements or walk in a straight line by placing the heel of one foot directly in front of the toes of the other foot. Given these signs and symptoms, which of the following vitamin deficiencies is most likely in this patient? A. folate B. vitamin B1 C. vitamin B2 D. vitamin B6 E. vitamin B12
Answer B: The patient is exhibiting symptoms of Wernicke encephalopathy resulting from deficiency in thiamin intake. Wernicke encephalopathy is a syndrome characterized by ataxia, ophthalmoplegia, nystagmus, and confusion.
You are the attending physician in the ER. You are examining a 48-year-old man brought by his wife because of a recent change in his mental status. Physical examination shows horizontal and vertical nystagmus, bilateral facial nerve palsy, and truncal ataxia. The most likely explanation for these findings is a deficiency in which of the following vitamins? A. folate B. vitamin B1 C. vitamin B6 D. vitamin C E. vitamin D
Answer B: The patient is suffering from Wernicke encephalopathy. Wernicke encephalopathy is most commonly found in chronic alcoholics due to their poor dietetic lifestyles. Wernicke encephalopathy is a syndrome characterized by ataxia, ophthalmoplegia, nystagmus, and confusion. If the disorder is left untreated, it will progress to Wernicke-Korsakoff syndrome which includes impairment of short-term memory, psychosis, coma, and eventually death.
As the ER physician you are tending to a 59-year-old female patient who has a broken left fibula. Upon physical exam you discover she also has multiple bruises on her arms, legs, and upper torso. She also complains of painful gums and significant bleeding whenever she brushes her teeth. She reports that she subsists on bouillon soup, tea, plain pasta, and dinner rolls. Blood work indicates that she is mildly anemic with microcytic erythrocytes. Given these signs and symptoms, this patient most likely is suffering from the effects of a deficiency in the activity of which of the following enzymes? A. branched-chain ketoacid dehydrogenase B. lysyl hydroxylase C. methionine synthase D. pyruvate dehydrogenase E. transketolase
Answer B: The signs and symptoms exhibited by this patient are indicative of scurvy which results from a deficiency of vitamin C (ascorbate). Vitamin C is a critical co-factor for the enzymes lysyl hydroxylase and prolyl hydroxylase that are required for the correct post-translational modification of collagen. Loss of collagen processing leads to defective connective tissue synthesis and also results in poor platelet adhesion to exposed sub-endothelial extracellular matrix resulting prolonged bleeding time. Often times vitamin C deficient patients also exhibit mild anemia due to the role of vitamin C in the process of intestinal absorption of Fe2+ iron.
Wernicke encephalopathy results from a deficiency of vitamin B1. Which of the following represents classical symptoms associated with this disorder? A. megaloblastic anemia B. nausea, peripheral neuropathy, mental depression, ophthalmoplegia C. numbness, tingling, weakness, sore smooth tongue, anorexia, diarrhea, pallor of the skin and mucous membranes D. seizure disorders E. weight loss, diarrhea, dementia, and dermatitis
Answer B: Wernicke encephalopathy is most commonly found in chronic alcoholics due to their poor dietetic lifestyles. Wernicke encephalopathy is a syndrome characterized by ataxia, ophthalmoplegia, nystagmus, and confusion. If the disorder is left untreated, it will progress to Wernicke-Korsakoff syndrome which includes impairment of short-term memory, psychosis, coma, and eventually death.
A 60-year-old chronic smoker and alcoholic man suffering from odynophagia, insomnia, epigastric discomfort, and recurrent diarrhea presented to the outpatient department. Clinical examination revealed memory disorientation, stomatitis, glossitis, esophagitis, and exfoliative dermatitis with some vesicles on erythematous bases on photoexposed sites such as his hands shown in the attached image. These signs and symptoms are most likely the result of a deficiency in which of the following vitamins? A. biotin B. cobalamin C. niacin D. riboflavin E. thiamin
Answer C: A diet deficient in niacin (as well as tryptophan) leads to glossitis of the tongue (inflammation of the tongue leading to purplish discoloration), dermatitis, weight loss, diarrhea, depression, and dementia. The severe symptoms, depression, dermatitis, and diarrhea, are associated with the condition known as pellagra and are sometimes referred to as the 3 Ds of niacin deficiency.
As an essential component of the nucleotide analog, FAD, which of the following vitamins plays a major role in the transfer of reducing equivalents? A. folate B. vitamin B1 C. vitamin C2 D. vitamin B6 E. vitamin B12
Answer C: Flavin adenine dinucleotide is a derivative of the vitamin riboflavin (B2).
A dietary deficiency of vitamin C would result in a decrease in which of the following? A. amount of THF available for one-carbon metabolism B. conversion of norepinephrine to epinephrine C. conversion of proline to hydroxyproline D. production of creatine E. supply of "active formaldehyde" units
Answer C: The active form of vitamin C is ascorbic acid itself. The main function of ascorbate is as a reducing agent in a number of different reactions. Ascorbate is the cofactor for Cu+-dependent monooxygenases and Fe2+-dependent dioxygenases. Ascorbate has the potential to reduce cytochromes a and c of the respiratory chain as well as molecular oxygen. The most important reaction requiring ascorbate as a cofactor is the hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissue as well as for wound healing since synthesis of connective tissue is the first event in wound tissue remodeling
Which of the following represents a significant biochemical role of vitamin C? A. blood coagulation B. calcium homeostasis C. connective tissue production D. metabolic functions of copper E. steroid hydroxylation
Answer C: The active form of vitamin C is ascorbic acid itself. The main function of ascorbate is as a reducing agent in a number of different reactions. Ascorbate is the cofactor for Cu+-dependent monooxygenases and Fe2+-dependent dioxygenases. Ascorbate has the potential to reduce cytochromes a and c of the respiratory chain as well as molecular oxygen. The most important reaction requiring ascorbate as a cofactor is the hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissue as well as for wound healing since synthesis of connective tissue is the first event in wound tissue remodeling.
The vitamin involved in biochemical reactions concerned with the transfer of methyl, methylene, or formyl groups is a derivative of which of the following vitamins? A. α-lipoic acid B. biotin C. folic acid D. pyridoxine E. riboflavin
Answer C: The function of THF (synthesized from folic acid) derivatives is to carry and transfer various forms of one-carbon units during biosynthetic reactions. The one-carbon units are methyl, methylene, methenyl, formyl, or formimino groups.
The attached radiograph shows the typical bowed legs of an infant suffering from a deficiency in which of the following vitamins? A. A B. C C. D D. E E. K
Answer C: The main symptom of vitamin D deficiency in children is rickets. Rickets is characterized by improper mineralization during the development of the bones resulting in soft bones, muscle weakness (rickety myopathy or "floppy baby syndrome,"), and increased tendency for fractures (especially greenstick fractures). In toddlers with rickets, a common skeletal deformity is bowed legs as depicted in the radiograph.
As a physician volunteer in a free clinic, you are examining a 52-year-old homeless man. You note that he has numerous petechiae and suspect impaired collagen production. Given his poor dietary habits, you determine that he lacks adequate intake of vitamin C. For which of the following steps of collagen synthesis is ascorbic acid required? A. cross-linking lysine and hydroxylysine residues B. glycosylation of hydroxylysine residues C. hydroxylation of proline residues D. removal of the signal peptide from preprocollagen E. translocation of collagen peptides into the endoplasmic reticulum
Answer C: The most important reaction requiring ascorbate (vitamin C) as a cofactor is the hydroxylation of proline residues in collagen
Scurvy is due to a dietary deficiency of which vitamin? A. A B. B6 (pyridoxal phosphate) C. B12 (cobalamin) D. C E. D
Answer D: Deficiency in vitamin C leads to the disease scurvy due to the role of the vitamin in the posttranslational modification of collagens. Scurvy is characterized by easily bruised skin, muscle fatigue, soft swollen gums, decreased wound healing and hemorrhaging, osteoporosis, and anemia.
The terminal ileum was removed from a 50-year-old woman during excision of a tumor. About 3 years later, the patient was admitted to the hospital. She is very pale. Hemoglobin is 9 g/dL, MCV (mean corpuscular volume) has increased to 110 mm3 (110 fL). The provisional diagnosis is a vitamin deficiency. Which of the following vitamins is the most likely one causing the symptoms? A. A B. B1 C. B6 D. B12 E. K
Answer D: Deficiency of vitamin B12 results in hematological, neurological, and gastrointestinal effects. The hematologic symptoms include a low red blood cell count with large-sized macrocytic red blood cells as described. Absorption of vitamin B12 is relatively complicated. The large and not very lipophilic molecule is released from food by the low pH of the stomach and pepsin digestion and binds to R protein (also called haptocorrin). Pancreatic proteases digest these complexes and the liberated cobalamin (vitamin B12) now complexes with intrinsic factor (which is produced by gastric parietal cells) and is absorbed as such in the terminal ileum. Hence, vitamin B12 absorption will be low in this patient. Liver storage is thought to be sufficient for 3 to 6 years so that the 3-year latency of the anemia further supports a vitamin B12 deficiency. The water-soluble vitamins B1 and B6 (choices B and C) are absorbed in the duodenum by simple diffusion. Absorption of the lipid-soluble vitamins A and K (choices A and E) is supported by bile-acid-mixed micelles, although vitamin A and vitamin K3 do not heavily rely on bile acids and can also enter the enterocytes by simple diffusion. Additionally, of the stated choices, only vitamin B12 deficiency is associated with anemia.
The ability of rod cells in the eye to respond to light and transmit that response to the optic nerve requires that the 11-cis form of vitamin A be attached to which of the following proteins? A. cGMP phosphodiesterase B. Na+ channel C. rhodopsin D. scotopsin E. transducing
Answer D: Photoreception in the eye is the function of 2 specialized cell types located in the retina; the rod and cone cells. Both rod and cone cells contain a photoreceptor pigment in their membranes. The photosensitive compound of most mammalian eyes is a protein called opsin to which is covalently coupled an aldehyde of vitamin A. The opsin of rod cells is called scotopsin. The photoreceptor of rod cells is specifically called rhodopsin or visual purple. This compound is a complex between scotopsin and the 11-cis-retinal (also called 11-cis-retinene) form of vitamin A. Rhodopsin is a serpentine receptor imbedded in the membrane of the rod cell. Coupling of 11-cis-retinal occurs at 3 of the transmembrane domains of rhodopsin. Intracellularly, rhodopsin is coupled to a specific G-protein called transducin.
A 50-year-old woman was diagnosed 2 years ago with primary biliary cirrhosis. Given her diagnosis, she is at greatest risk for becoming deficient in which of the following? A. B1 (thiamin) B. B12 (cobalamin) C. C D. E E. niacin
Answer D: Vitamin E is a fat-soluble vitamin. In order for the fat-soluble vitamins to be absorbed from the intestines, they must be emulsified along with all the other fatty molecules in the diet. The primary mechanism for fat emulsification is the release of bile salts from the gallbladder in response to food intake. The bile salts are synthesized from cholesterol within hepatocytes and then transported to the gallbladder via the bile canaliculi. Thus, cirrhosis of the biliary circulatory system will lead to impaired absorption of fats, including fat-soluble vitamins such as vitamin E.
Vitamin K is necessary for normal blood coagulation. Which of the following processes of hemostasis is dependent on the activity of this vitamin? A. it complexes with platelets in the first wave of platelet aggregation B. it induces the release of von Willebrand factor C. it inhibits the activation of the fibrinolytic system D. it initiates the contact phase by activating factor XI (plasma thromboplastin antecedent) E. it is a required cofactor for the introduction of gla-residues into coagulation factors
Answer E: The major function of the K vitamins is in the maintenance of normal levels of the blood-clotting proteins, factors II, VII, IX, X, and protein C and protein S, which are synthesized in the liver as inactive precursor proteins. Conversion from inactive to active clotting factor requires a posttranslational modification of specific glutamate (E) residues. This modification is a carboxylation and the enzyme responsible requires vitamin K as a cofactor. The resultant modified E residues are g-carboxyglutamate (gla).
The activity of which of the following enzymes in the erythrocyte will be decreased in patients with a deficiency of thiamin? A. adenosine deaminase B. aspartate aminotransferase (AST) C. pyruvate kinase D. transaldolase E. transketolase
Answer E: The pentose phosphate pathway (PPP) is a critical pathway of glucose oxidation within erythrocytes due to it being required for the generation of NADPH. The transketolase enzyme, involved in the nonoxidative reactions of the PPP, requires TPP as a cofactor.
Which of the following laboratory findings is most likely in a 37-year-old woman with a thiamin deficiency? A. decreased plasma concentration of alanine B. increased erythrocyte transketolase activity C. increased leukocyte α-ketoglutarate dehydrogenase activity D. increased plasma concentration of glucose E. increased plasma concentrations of pyruvate and lactate
Answer E: Thiamin serves as the precursor for TPP. TPP is necessary as a cofactor for the pyruvate dehydrogenase complex (PDHc) and, therefore, a deficiency thiamin results in impaired oxidation of pyruvate. This will lead to increased plasma concentrations of pyruvate. When lactate from erythrocyte and skeletal muscle metabolism reaches the liver, it will not be readily converted to pyruvate due to the reduced pyruvate oxidative capacity leading to elevated plasma lactate. In addition, the excess pyruvate will be a substrate for lactate dehydrogenase, resulting in additionally increased levels of pyruvate.
A strict vegan diet restricts the intake of meat, eggs, milk, cheese, or other animal-derived foods. You are examining your patient who follows this particular dietary regimen. Urine analysis shows increased concentration of methylmalonic acid. This finding is indicative of which of the following? A. excess methylmalonate in the diet B. fatty acid deficiency C. folate deficiency D. protein deficiency E. vitamin B12 (cobalamin) deficiency
Answer E: Vitamin B12 is a critical coenzyme in the methionine synthase and methylmalonyl-CoA mutase-catalyzed reactions. Therefore, a deficiency in B12 results in defective activity of these 2 enzymes. Methylmalonyl-CoA mutase is involved in the conversion of propionyl-CoA to the TCA cycle intermediate, succinyl-CoA, specifically the reaction whereby methylmalonyl-CoA is converted to succinyl-CoA. The inability to convert methylmalonyl-CoA to succinyl-CoA leads to excess excretion of the metabolite in the urine as well as increased concentrations in the blood.
Wernicke encephalopathy syndrome is caused by a deficiency of which of the following? A. biotin B. cobalamin C. pyridoxal phosphate D. riboflavin E. thiamine
Answer E: Wernicke encephalopathy results from a dietary deficiency in thiamine. The disorder is most commonly found in chronic alcoholics due to their poor dietetic lifestyles. Wernicke encephalopathy is a syndrome characterized by ataxia, ophthalmoplegia, nystagmus, confusion, and impairment of short-term memory.
A deficiency in which of the following vitamins would most likely be associated with prolonged clotting times, hemorrhaging, and anemia? A. α-lipoic acid B. C C. D D. E E. K
The major role of the K vitamins is in the maintenance of normal levels of the blood-clotting proteins, factors II, VII, IX, X, and protein C and protein S, which are synthesized in the liver as inactive precursor proteins. Conversion from inactive to active clotting factor requires a posttranslational modification of specific glutamate (E) residues. This modification is a carboxylation and the enzyme responsible requires vitamin K as a cofactor. The resultant modified E residues are γ-carboxyglutamate (gla). Thus, a deficiency in vitamin K will result in prolonged bleeding and the potential for hemorrhage.
