Correct answer = E. The elevated excretion of orotic acid and low activity of uridine monophosphate (UMP) synthase indicate that the patient has orotic aciduria, a very rare genetic disorder affecting de novo pyrimidine synthesis. Deficiencies in one or both catalytic domains of UMP synthase leave the patient unable to synthesize pyrimidines. Uridine, a pyrimidine nucleoside, is a useful treatment because it bypasses the missing activities and can be salvaged to UMP, which can be converted to all the other pyrimidines. Although thymidine is a pyrimidine nucleoside, it cannot be converted to other pyrimidines. Hypoxanthine, guanine, and adenine are all purine bases and cannot be converted to pyrimidines.
2.5. What laboratory test would help in distinguishing an orotic aciduria caused by ornithine transcarbamylase deficiency from that caused by uridine monophosphate synthase deficiency?
Blood ammonia level would be expected to be elevated in ornithine transcarbamylase deficiency that affects the urea cycle but not in uridine monophosphate synthase deficiency.
UNIT V Integration of Metabolism Metabolic Effects of Insulin and Glucagon 23
For additional ancillary materials related to this chapter, please visit thePoint.
I. OVERVIEW
Four major tissues play a dominant role in fuel metabolism: liver, adipose, muscle, and brain. These tissues contain unique sets of enzymes, such that each tissue is specialized for the storage, use, or generation of specific fuels. These tissues do not function in isolation but rather form part of a network in which one tissue may provide substrates to another or process compounds produced by other tissues. Communication between tissues is mediated by the nervous system, by the availability of circulating substrates, and by variation in the levels of plasma hormones (Fig. 23.1). The integration of energy metabolism is controlled primarily by the actions of two peptide hormones, insulin and glucagon (secreted in response to changing substrate levels in the blood), with the catecholamines epinephrine and norepinephrine (secreted in response to neural signals) playing a supporting role. Changes in the circulating levels of these hormones allow the body to store energy when food is abundant or to make stored energy available such as during survival crises (for example, famine, severe injury, and “fight-or-flight” situations). This chapter describes the structure, secretion, and metabolic effects of the two hormones that most profoundly affect energy metabolism.
II. INSULIN
Insulin is a peptide hormone produced by the β cells of the islets of Langerhans, which are clusters of cells embedded in the endocrine portion of the pancreas (Fig. 23.2). [Note: “Insulin” is from the Latin for island.] The islets make up only about 1%–2% of the total cells of the pancreas. Insulin is the most important hormone coordinating the use of fuels by tissues. Its metabolic effects are anabolic, favoring, for example, synthesis of glycogen, triacylglycerol (TAG), and protein.
A. Structure
Insulin is composed of 51 amino acids arranged in two polypeptide chains, designated A (21 amino acids) and B, which are linked together by two disulfide bonds (Fig. 23.3A). The insulin molecule also contains an intramolecular disulfide bond between amino acid residues of the A chain. [Note: Insulin was the first peptide for which the primary structure was determined and the first therapeutic molecule made by recombinant DNA technology (see p. 486).]
B. Synthesis