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Regulation of Hormone Levels in the Blood Thehalf-life of most hormones in the blood is relativelyshort. For example, if radioactively labeled insulinis injected into an animal, one can determine thatwithin 30 min half the hormone has disappearedfrom the blood.(a) What is the importance of the relativelyrapid inactivation of circulating hormones?(b) In view of this rapid inactivation, how canthe circulating hormone level be kept constantunder normal conditions?(c) In what ways can the organism make possible rapid changes in the level of circulating hormones?9. Water-Soluble versus Lipid-Soluble HormonesOn the basis of their physical properties, hormonesfall into one of two categories: those that are verysoluble in water but relatively insoluble in lipids(e.g., epinephrine) and those that are relativelyinsoluble in water but highly soluble in lipids (e.g.,steroid hormones).
In their role as regulators ofcellular activity, most water-soluble hormones donot penetrate into the interior of their target cells.The lipid-soluble hormones, by contrast, do penetrate into their target cells and ultimately act inthe nucleus. What is the correlation between solubility, the location of receptors, and the mode ofaction of the two classes of hormones?10. Hormone Experiments in Cell-Free Systems Inthe 1950s, Earl Sutherland and his colleagues carried out pioneering experiments to elucidate themechanism of action of epinephrine and glucagon.In the light of our current understanding of hormone action as described in this chapter, interpreteach of the experiments described below. Identifythe components and indicate the significance of theresults.(a) The addition of epinephrine to a homogenateor broken-cell preparation of normal liver resultedin an increase in the activity of glycogen phosphorylase.
However, if the homogenate was first centrifuged at a high speed and epinephrine or glucagon was added to the clear supernatant fractioncontaining phosphorylase, no increase in phosphorylase activity was observed.(b) When the particulate fraction sedimentedfrom a liver homogenate by centrifugation was separated and treated with epinephrine, a new substance was produced. This substance was isolatedand purified. Unlike epinephrine, this substanceactivated glycogen phosphorylase when added tothe clear supernatant fraction of the homogenate.(c) The substance obtained from the particulatefraction was heat-stable; that is, heat treatmentdid not prevent its capacity to activate phosphorylase. (Hint: Would this be the case if the substancewere a protein?) The substance appeared nearlyidentical to a compound obtained when pure ATPwas treated with barium hydroxide.
(Figure 12-6will be helpful.)11. Effect of Dibutyryl-cAMP versus cAMP on Intact Cells The physiological effects of the hormoneepinephrine should in principle be mimicked bythe addition of cAMP to the target cells. In practice, the addition of cAMP to intact target cells elicits only a minimal physiological response. Why?When the structurally related derivative dibutyryl-cAMP (shown below) is added to intact cells,the expected physiological responses can readily beseen.
Explain the basis for the difference in cellu-Chapter 22 Integration and Hormonal Regulation of Mammalian Metabolismlar response to these two substances. DibutyrylcAMP is a widely used derivative in studies ofcAMP function.NH—C-CH 2 —CH2 - C H 3O-CH 2O=PO"OO-C-CH2-CH2-CH3ODibutyryl-cAMP12. Effect of Cholera Toxin on Adenylate CyclaseThe gram-negative bacterium Vibrio cholerae produces a protein, cholera toxin (Mr 90,000), responsible for the characteristic symptoms of cholera:extensive loss of body water and Na + through continuous, debilitating diarrhea.
If body fluids andNa + are not replaced, severe dehydration willoccur; untreated, the disease is often fatal. Whenthe cholera toxin gains access to the human intestinal tract it binds tightly to specific sites in theplasma membrane of the epithelial cells lining thesmall intestine, causing adenylate cyclase to undergo activation that persists for hours or days.(a) What is the effect of cholera toxin on thelevel of cAMP in the intestinal cells?(b) Based on the information above, can yousuggest how cAMP normally functions in intestinalepithelial cells?(c) Suggest a possible treatment for cholera.13.
Metabolic Differences in Muscle and Liver in a'Tight or Flight" Situation During a "fight orflight" situation, the release of epinephrine promotes glycogen breakdown in the liver, heart, andskeletal muscle. The end product of glycogenbreakdown in the liver is glucose. In contrast, theend product in skeletal muscle is pyruvate.787(a) Why are different products of glycogenbreakdown observed in the two tissues?(b) What is the advantage to the organism during a "fight or flight" condition of having these specific glycogen breakdown routes?14. Excessive Amounts of Insulin Secretion: Hyperinsulinism Certain malignant tumors of the pancreas cause excessive production of insulin by the pcells.
Affected individuals exhibit shaking andtrembling, weakness and fatigue, sweating, andhunger. If this condition is prolonged, brain damage occurs.(a) What is the effect of hyperinsulinism on themetabolism of carbohydrate, amino acids, and lipids by the liver?(b) What are the causes of the observed symptoms? Suggest why this condition, if prolonged,leads to brain damage.15. Thermogenesis Caused by Thyroid HormonesThyroid hormones are intimately involved in regulating the basal metabolic rate. Liver tissue of animals given excess thyroxine shows an increasedrate of O2 consumption and increased heat output(thermogenesis), but the ATP concentration in thetissue is normal.
Different explanations have beenoffered for the thermogenic effect of thyroxine. Oneis that excess thyroid hormone causes uncouplingof oxidative phosphorylation in mitochondria. Howcould such an effect account for the observations?Another explanation suggests that the thermogenesis is due to an increased rate of ATP utilizationby the thyroid-stimulated tissue. Is this a reasonable explanation? Why?16. Function of Prohormones What are the possible advantages in the synthesis of hormones asprohormones or preprohormones?17.
Action of AminophyllineAminophylline, apurine derivative resembling theophylline of tea, isoften administered together with epinephrine toindividuals with acute asthma. What is the purpose and biochemical basis for this treatment?C H A P T E RRegulation of Gene ExpressionOf the 4,000 genes in the typical bacterial genome or the estimated100,000 genes in the human genome, only a fraction are expressed atany given time.
Some gene products have functions that mandate theirpresence in very large amounts. The elongation factors required forprotein synthesis, for example, are among the most abundant proteinsin bacteria. Other gene products are needed in much smaller amounts;for instance, a cell may contain only a few molecules of the enzymesthat repair rare DNA lesions. Requirements for a given gene productmay also change with time.
The need for enzymes in certain metabolicpathways may wax or wane as food sources change or are depleted.During development in a multicellular eukaryote, some proteins thatinfluence cellular differentiation are present for only a brief time in asmall subset of an organism's cells.
The specialization of some cells forparticular functions can also dramatically affect the need for variousgene products, one example being the uniquely high concentration ofhemoglobin in erythrocytes.The regulation of gene expression is a critical component in regulating cellular metabolism and in orchestrating and maintaining thestructural and functional differences that exist in cells during development. Given the high energetic cost of protein synthesis, regulation ofgene expression is essential if the cell is to make optimal use of available energy.Regulating the concentration of a cellular protein involves a delicate balance of many processes.
There are at least six potential pointsat which the amount of protein can be regulated (Fig. 27-1): synthesisof the primary RNA transcript, posttranscriptional processing ofmRNA, mRNA degradation, protein synthesis (translation), posttranslational modification of proteins, and protein degradation. The concentration of a given protein is controlled by regulatory mechanisms atany or all of these points. Some of these mechanisms have been examined in previous chapters.
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