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FIGURE 16-17 Biological tethers. The cofactors lipoate, biotin, and the combination of ^-mercaptoethylamine and pantothenate form long, flexible arms in the enzymes to which they are covalently bound, acting as tethers that move intermediates from one active site to the next. The group shaded pink is in each case the point of attachment of the activated intermediate to the tether.

chromatography (see Fig. 3-18c) based on biotin's strong affinity for avidin. The protein is then eluted from the column with an excess of free biotin. The very high affinity of biotin for avidin is also used in the laboratory in the form of a molecular glue that can hold two structures together (see Fig. 19-25).

SUMMARY 16.2 Reactions of the Citric Acid Cycle

■ The citric acid cycle (Krebs cycle, TCA cycle) is a nearly universal central catabolic pathway in which compounds derived from the breakdown of carbohydrates, fats, and proteins are oxidized to CO2, with most of the energy of oxidation temporarily held in the electron carriers FADH2 and NADH. During aerobic metabolism, these electrons are transferred to

O2 and the energy of electron flow is trapped as ATP.

■ Acetyl-CoA enters the citric acid cycle (in the mitochondria of eukaryotes, the cytosol of prokaryotes) as citrate synthase catalyzes its condensation with oxaloacetate to form citrate.

■ In seven sequential reactions, including two decarboxylations, the citric acid cycle converts citrate to oxaloacetate and releases two CO2. The pathway is cyclic in that the intermediates of the cycle are not used up; for each oxalo-acetate consumed in the path, one is produced.

■ For each acetyl-CoA oxidized by the citric acid cycle, the energy gain consists of three molecules of NADH, one FADH2, and one nucleoside triphosphate (either ATP or GTP).

■ Besides acetyl-CoA, any compound that gives rise to a four- or five-carbon intermediate of the citric acid cycle—for example, the breakdown products of many amino acids—can be oxidized by the cycle.

■ The citric acid cycle is amphibolic, serving in both catabolism and anabolism; cycle intermediates can be drawn off and used as the starting material for a variety of biosynthetic products.

■ When intermediates are shunted from the citric acid cycle to other pathways, they are replenished by several anaplerotic reactions, which produce four-carbon intermediates by carboxylation of three-carbon compounds; these reactions are catalyzed by pyruvate carboxylase, PEP carboxykinase, PEP carboxylase, and malic enzyme. Enzymes that catalyze carboxylations commonly employ biotin to activate CO2 and to carry it to acceptors such as pyruvate or phosphoenolpyruvate.

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Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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