A 52-year-old woman comes to the office with a 2-month history of skin rash that worsens with sun exposure. Her family says that lately she has become irritable and hostile and has had episodes of disorientation. The patient does not use tobacco or recreational drugs but has been drinking a half bottle of gin daily. Further questioning reveals poor nutritional intake and intermittent diarrhea. The patient restricts her diet for weight control. BMI is 17 kg/m2. On examination, she has a well-demarcated, hyperpigmented, scaly rash on the hands, forearms, and upper chest. It is determined that the patient is deficient in a vitamin that is used to synthesize the NAD+ coenzyme. Which of the following substances can also be used as a precursor during production of this coenzyme?
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Pellagra ("rough skin" in Italian vernacular) is due to niacin deficiency and is characterized by 3 Ds: dermatitis, diarrhea, and dementia:
Dermatitis is bilateral and symmetric on sun-exposed areas of the body and is characterized by rough, thick, scaly skin.
Diarrhea is due to atrophy (and occasional ulceration) of columnar epithelium of the gastrointestinal tract.
Dementia is due to neuronal degeneration in the brain and spinal cord, with lesions like those associated with pernicious anemia.
Niacin (nicotinic acid, or vitamin B3) is an essential component of the coenzymes NAD and NADP, which participate in redox metabolism. Specifically, NAD functions as a coenzyme for dehydrogenases involved in the metabolism of fats, carbohydrates, and amino acids; NADP is crucial in the hexose-monophosphate shunt of glucose metabolism and for biosynthesis of cholesterol and fatty acids.
Niacin can be obtained through dietary intake or synthesized endogenously from tryptophan. In developing countries, niacin deficiency is seen in populations that subsist primarily on corn products (niacin in corn occurs in a bound, unabsorbable form). In developed countries, it is primarily seen in patients with impaired nutritional intake (eg, alcohol use disorder, chronic illness). Pellagra can also be seen occasionally in those with carcinoid syndrome, prolonged isoniazid therapy, or Hartnup disease.
(Choice A) Arginine is a nonessential amino acid and a precursor of nitric oxide, urea, ornithine, and agmatine. It is also necessary for the formation of creatine.
(Choice B) Carotene is the precursor to vitamin A. Carotene deficiency may result in night blindness and immune dysfunction.
(Choice C) Cholesterol is the precursor to steroid hormones.
(Choice D) Orotic acid is a precursor of pyrimidine. Hereditary orotic aciduria occurs due to impairment of the enzyme uridine monophosphate synthetase, which synthesizes pyrimidines from orotic acid. The accumulation of orotic acid leads to megaloblastic anemia, developmental delay, and failure to thrive.
(Choice E) Phenylalanine is an essential amino acid and the precursor to tyrosine, an amino acid necessary for the formation of catecholamines. Phenylketonuria (PKU) occurs due to impairment of the enzyme phenylalanine hydroxylase, which synthesizes tyrosine from phenylalanine.
Educational objective:
Niacin (vitamin B3) can be synthesized endogenously from tryptophan and is an essential component of NAD and NADP. A deficiency of this vitamin results in pellagra, which is characterized by dermatitis, diarrhea, and dementia.