Obesity and the Regulation of Body Mass

TIn the United States population, 30 of adults are obese and another 35 are overweight. (Obesity is defined in terms of body mass index (BMI) BMI weight in kg (height in m)2. A BMI below 25 is considered normal 25 to 30 is overweight, and greater than 30, obese.) Obesity is life-threatening. It significantly increases the chances of developing type II diabetes as well as heart attack, stroke, and cancers of the colon, breast, prostate, and endometrium. Consequently, there is great interest in...

Leptin Triggers a Signaling Cascade That Regulates Gene Expression

Plasma Membrane Leptin Receptor Monomer

The leptin signal is transduced by a mechanism also used by receptors for interferon and growth factors, the JAK-STAT system Fig. 23-34 see Fig. 12-9 . The lep-tin receptor, which has a single transmembrane segment, dimerizes when leptin binds to the extracellular domain of two monomers. Both monomers are phos-phorylated on a Tyr residue of the intracellular domain by a Janus kinase JAK . The -Tyr residues become docking sites for three proteins that are signal transducers and activators of...

How Is a Hormone Discovered The Arduous Path to Purified Insulin

Insulin Purification From Pancreas

Millions of people with type I insulin-dependent diabetes mellitus inject themselves daily with pure insulin to compensate for the lack of production of this critical hormone by their own pancreatic 3 cells. Insulin injection is not a cure for diabetes, but it allows people who otherwise would have died young to lead long and productive lives. The discovery of insulin, which began with an accidental observation, illustrates the combination of serendipity and careful experimentation that led to...

The Pancreas Secretes Insulin or Glucagon in Response to Changes in Blood Glucose

When glucose enters the bloodstream from the intestine after a carbohydrate-rich meal, the resulting increase in blood glucose causes increased secretion of insulin and decreased secretion of glucagon . Insulin release by the pancreas is largely regulated by the level of glucose in the blood supplied to the pancreas. The peptide hormones insulin, glucagon, and somatostatin are produced by clusters of specialized pancreatic cells, the islets of Langerhans Fig. 23-24 . Each cell type of the...

If Your Diet Is Rich In Alanine But Deficient In Aspartate Will You Show Signs Of Aspartate Deficiency

Holmes, F.L. 1980 Hans Krebs and the discovery of the ornithine cycle. Fed. Proc. 39, 216-225. A medical historian reconstructs the events leading to the discovery of the urea cycle. Kirsch, J.F., Eichele, G., Ford, G.C., Vincent, M.G., Jansonius, J.N., Gehring, H., amp Christen, P. 1984 Mechanism of action of aspartate aminotransferase proposed on the basis of its spatial structure. J. Mol. Biol. 174, 497-525. Morris, S.M. 2002 Regulation of enzymes of the urea cycle and arginine metabolism....

Excess Uric Acid Causes Gout

Long thought, erroneously, to be due to high living, gout is a disease of the joints caused by an elevated concentration of uric acid in the blood and tissues. The joints become inflamed, painful, and arthritic, owing to the abnormal deposition of sodium urate crystals. The kidneys are also affected, as excess uric acid is deposited in the kidney tubules. Gout occurs predominantly in males. Its precise cause is not known, but it often involves an underexcretion of urate. A genetic deficiency of...

Short Term Eating Behavior Is Set by Ghrelin and PYY336

Ghrelin is a peptide hormone 28 amino acids produced in cells lining the stomach. It was originally recognized as the stimulus for the release of growth hormone ghre is the Proto-Indo-European root of grow , then subsequently shown to be a powerful appetite stimulant that works on a shorter time scale between meals than leptin and insulin. Ghrelin receptors are located in the pituitary gland presumably mediating growth hormone release and in the hypothalamus affecting appetite , as well as in...

Digestion Mobilization and Transport of Fats

Cells can obtain fatty acid fuels from three sources fats consumed in the diet, fats stored in cells as lipid droplets, and fats synthesized in one organ for export to another. Some species use all three sources under various circumstances, others use one or two. Vertebrates, for example, obtain fats in the diet, mobilize fats stored in specialized tissue adipose tissue, consisting of cells called adipocytes , and, in the liver, convert excess dietary carbohydrates to fats for export to other...

Triacylglycerols Provide Stored Energy and Insulation

Guinea Pig Adipocytes

In most eukaryotic cells, triacylglycerols form a separate phase of microscopic, oily droplets in the aqueous cytosol, serving as depots of metabolic fuel. In vertebrates, specialized cells called adipocytes, or fat cells, store large amounts of triacylglycerols as fat droplets that nearly fill the cell Fig. 10-3a . Triacylglycerols are also stored as oils in the seeds of many types of plants, providing energy and biosynthetic precursors during seed germination Fig. 10-3b . Adipocytes and...

Insulin Acts in the Arcuate Nucleus to Regulate Eating and Energy Conservation

Insulin Receptors Nucelus

Insulin secretion reflects both the size of fat reserves adiposity and the current energy balance blood glucose level . Insulin acts on insulin receptors in the hypothalamus to inhibit eating Fig. 23-33 . Insulin receptors in the orexigenic neurons of the arcuate nucleus inhibit the release of NPY, and insulin receptors in the anorexigenic neurons stimulate a-MSH production, thereby decreasing fuel intake and increasing thermo-genesis. By mechanisms discussed in Section 23.3, insulin also...

Regulation of the Citric Acid Cycle

Tca Cycle Nh4

As we have seen in Chapter 15, the regulation of key enzymes in metabolic pathways, by allosteric effectors and by covalent modification, ensures the production of intermediates at the rates required to keep the cell in a stable steady state while avoiding wasteful overproduction. The flow of carbon atoms from pyruvate into and through the citric acid cycle is under tight regulation at two levels the conversion of pyruvate to acetyl-CoA, the starting material for the cycle the pyruvate...

Degradation of Purines and Pyrimidines Produces Uric Acid and Urea Respectively

Purine nucleotides are degraded by a pathway in which they lose their phosphate through the action of 5'-nucleotidase Fig. 22-45 . Adenylate yields adenosine, which is deaminated to inosine by adenosine deami-nase, and inosine is hydrolyzed to hypoxanthine its purine base and d-ribose. Hypoxanthine is oxidized successively to xanthine and then uric acid by xanthine oxidase, a flavoenzyme with an atom of molybdenum and four iron-sulfur centers in its prosthetic group. Molecular oxygen is the...

Chelating Agents Peripheral Proteins

Peripheral Proteins

FIGURE 11-5 Asymmetric distribution of phospholipids between the inner and outer monolayers of the erythrocyte plasma membrane. The distribution of a specific phospholipid is determined by treating the intact cell with phospholipase C, which cannot reach lipids in the inner monolayer leaflet but removes the head groups of lipids in the outer monolayer. The proportion of each head group released provides an estimate of the fraction of each lipid in the outer monolayer. FIGURE 11-5 Asymmetric...

Leptin Stimulates Production of Anorexigenic Peptide Hormones

Arcuate Nucleus Pathway

Two types of neurons in the arcuate nucleus control fuel intake and metabolism Fig. 23-33 . The orexigenic appetite-stimulating neurons stimulate eating by producing and releasing neuropeptide Y NPY , which causes the next neuron in the circuit to send the signal to the brain, Eat The blood level of NPY rises during starvation, and is elevated in both ob ob and db db mice. The high NPY concentration presumably underlies the obesity of these mice, who eat voraciously. The anorexigenic...

Triacylglycerol Cycle

Triacylglycerol Cycle

Flux through this tri-acylglycerol cycle between adipose tissue and liver may be quite low when other fuels are available and the release of fatty acids from adipose tissue is limited, but as noted above, the proportion of released fatty acids that are reesterified remains roughly constant at 75 under all metabolic conditions. The level of free fatty acids in the blood thus reflects both the rate of release of fatty acids and the balance between the synthesis...

The Lipostat Theory Predicts the Feedback Regulation of Adipose Tissue

Lipostat Theory

The lipostat theory postulates a mechanism that inhibits eating behavior and increases energy consumption whenever body weight exceeds a certain value the set point the inhibition is relieved when body weight drops below the set point Fig. 23-30 . This theory predicts that a feedback signal originating in adipose tissue influences the brain centers that control eating behavior and activity metabolic and motor . The first such factor, leptin, was discovered in 1994, and several others are now...

Adiponectin Acts through AMPK

Carnitine Acyltransferase Activity

Adiponectin is a peptide hormone 224 amino acids produced almost exclusively in adipose tissue. It circulates in the blood and powerfully affects the metabolism of fatty acids and carbohydrates in liver and muscle. Adiponectin increases the uptake of fatty acids from the blood by myocytes and the rate at which fatty acids undergo 3 oxidation in the muscle. It also blocks fatty acid synthesis and gluconeogenesis in hepatocytes, and it stimulates glucose uptake and catabolism in muscle and liver...

Nucleotides Are Poor Sources Of Energy

Structure Azaserine

a What is the role of p-aminobenzoate in these bacteria Hint See Fig. 18-16 . b Why does AICAR accumulate in the presence of sul-fanilamide c Why are the inhibition and accumulation reversed by addition of excess p-aminobenzoate 12. Pathway of Carbon in Pyrimidine Biosynthesis Predict the locations of 14C in orotate isolated from cells grown on a small amount of uniformly labeled 14C succinate. Justify your prediction. 13. Nucleotides As Poor Sources of Energy Under starvation conditions,...