biochemfinal

(5) FETAL V. MATERNAL Hb (a) Which hemoglobin has a higher affinity for oxygen under physiological conditions, HbA or HbF? Explain. (b) What is the physiological significance of the different O2 affinities? (c )When all the BPG is carefully removed from samples of HbA and HbF, the measured O2-saturation curves (and consequently the O2 affinities) are displaced to the left. However, HbA now has a greater affinity for oxygen than does HbF. When BPG is reintroduced, the O2-saturation curves return to normal, as shown in the graph. What is the effect of BPG on the O2 affinity of hemoglobin? How can the above information be used to explain the different O2 affinities of fetal and maternal hemoglobin

(a) HbF has a higher O2 affinity than HbA. In other words, at identical O2 concentrations, HbF binds more oxygen than doesHbA. Thus, HbF must bind oxygen more tightly (with higher affinity) than HbA under physiological conditions. (b) The higher O2 affinity of HbF ensures that oxygen will flow from maternal blood to fetal blood in the placenta. For maximal O2 transport, the oxygen pressure at which fetal blood approaches full saturation must be in the region where the O2 affinity of HbA is low. (c) HbA binds BPG more tightly than does HbF. Differential binding ofBPG to the two hemoglobins may determine the difference in their O2 affinities

ester linkage

-COOH

(13) Dependence of G on pH: The free energy released by the hydrolysis of ATP under standard conditions at pH 7.0 is 30.5 kJ/mol. If ATP is hydrolyzed under standard conditions except at pH 5.0, is more or less free energy released? Explain.

LESS. Because H+ ions are produced in the reaction, the lower the pH at which the reaction proceeds—that is, the higher the [H+]—the more the equilibrium shifts toward reactants. As a result, at lower pH the reaction does not proceed as far toward products, and less free energy is released.

hemoglobin binding to oxygen and hydrogen ions

Oxygen and H are not bound at the same sites in hemoglobin. Oxygen binds to the iron atoms of the hemes, whereas H binds to any of several amino acid residues in the protein. A major contribution to the Bohr effect is made by His146 (His HC3) of the subunits. When protonated, this residue forms one of the ion pairs—to Asp94 (Asp FG1)—that helps stabilize deoxyhemoglobin in the T state (Fig. 5-9). The ion pair stabilizes the protonated form of His HC3, giving this residue an abnormally high pKa in the T state. As the concentration of H rises, protonation of His HC3 promotes release of oxygen by favoring a transition to the T state. Protonation of the amino-terminal residues of the subunits, certain other His residues, and perhaps other groups has a similar effect. Thus we see that the four polypeptide chains of hemoglobin communicate with each other about not only O2 binding to their heme groups but also H binding to specific amino acid residues

alanine

-CH3, A, Ala fully protonated: H3N,COOH fully deprotonated: H2N,COO- pKa = carb2.35, amino9.87 (b)At pH 1.0, 1.3 pH units below the pKa of the carboxyl group, more than 90% of the carboxyl groups are protonated, and protonated amino groups predominate by a factor of more than 107. (c)At pH 6.2 the zwitterion predominates. This is 4 pH units above the pKa of the carboxyl group, so the vast majority of carboxyl groups are deprotonated. It is 3.5 pH units below the pKa of the amino group, so the vast majority of amino groups are protonated. (d)At pH 8.02 the zwitterion still predominates. The carboxyl groups are deprotonated and, with the pH still 1.6 units below the pKa of the amino group, the vast majority of amino groups are protonated. (e)At pH 11.9, 2.2 pH units above the pKa of the amino group, the vast majority of amino groups are deprotonated; and the carboxyl groups, at 9.6 pH units above their pKa, remain deprotonated

thioester

-COSH compound containing an ester linkage to a sulfur rather than an oxygen ex: Acetyl CoA

myoglobin

-a muscle pigment that holds one O2 molecule more tightly than hemoglobin does, and therefore only gives up its oxygen once hemoglobin has given up all its oxygen

(2) pH from H

-logH

(2) H from pH

10^(-pH)

buffers

A chemical substance that resists changes in pH by accepting hydrogen ions from or donating hydrogen ions to solutions

(1) Identify the chiral center in isoproterenol. Why do the two enantiomers have such radically different bioactivity

A chiral center, or chiral carbon, is a carbon atom that is bonded to four different groups. A molecule with a single chiral center has two enantiomers, designated Dand L The bioactivity of a drug is the result of interaction with a biological "receptor," a protein molecule with a binding site that is also chiral and stereospecific. The interaction of the Disomerof a drug with a chiral receptor site will differ from the interaction of the L isomer with that site

(1) What is the relationship between MRS and the Delta G of the binding reaction? Specifically, would a more negative Delta G correspond to a higher or lower MRS? Explain your reasoning

A more negative DeltaG°corresponds to a larger Keq for the binding reaction, so the equilibrium is shifted more toward products and tighter binding-and thus greater sweetness and higher MRS.

carbon monoxide

CO binds to one or two subunits of a hemoglobin tetramer, the affinity for O2 is increased substantially in the remaining subunits. Thus, a hemoglobin tetramer with two bound CO molecules can efficiently bind O2 in the lungs—but it releases very little of it in the tissues CO has similar size and shape to O2; it can fit to the same binding site CO binds over 20,000 times better than O2 because the carbon in CO has a filled lone electron pair that can be donated to vacant d-orbitals on the Fe2+ Protein pocket decreases affinity for CO, but is still binds about 250 times better than oxygen CO is highly toxic as it competes with oxygen. It blocks the function of myoglobin, hemoglobin, and mitochondrial cytochromes that are involved in oxidative phosphorylation

(2) Ethanol is more soluble in water than ethane

Ethanol is polar; ethane is not. The ethanol —OH group can hydrogen-bond with water

colligative properties

For example, when a significant fraction of the molecules at the surface of an aqueous solution are not water but solute, the tendency of water molecules to escape into the vapor phase—that is, the vapor pressure—is lowered the tendency of water molecules to move from the aqueous phase to the surface of a forming ice crystal is reduced when some of the molecules that collide with the crystal are solute, not water. In that case, the solution will freeze more slowly than pure water and at a lower temperature

(2) Moles from H+

H = 10^-pH = MOLES In 15mL: (.015L)(H+ MOLARITY) =number of Moles in solution

(2) pH of 10.0 mL sample of gastric juice was titrated with 0.1 M NaOH to neutrality; 7.2 mL of NaOH was required

Multiplying volume (L) by molar concentration (mol/L) gives the X number of moles in that volume of solution (0.010 L)X = (0.0072 L)(0.1 mol/L) pH = -logX

(2) pH of a solution preparedby diluting 3.0 mL of 2.5 MHCl to a final volume of 100 mL with H2O

Multiplying volume (L) by molar concentration (mol/L) gives the number of moles in that volume of solution:3.0 mL x2.5 M HCl = 7.5M of H+. (In 100 mL of solution =0.075) pH = -log[.075]

(1) The physical properties (C, H, and N analysis, melting point, solubility, etc.) of Dexedrine and Benzedrine were identical. The recommended oral dosage of Dexedrine (which is still available) was 5 mg / day, but the recommended dosage of Benzedrine (no longer available) was twice that.Apparently, it required considerably more Benzedrine than Dexedrine to yield the same physiologi-cal response. Explain this apparent contradiction

Only one of the two enantiomers of the drug molecule (which has a chiral center) is physiologically active, for reasons described in the answer to Problem 3 (interaction with a stereospecific receptor site). Dexedrine, as manufactured, consists of the single enantiomer (D-amphetamine) recognized by the receptor site. Benzedrine was a racemic mixture (equal amounts of D and L isomers), so a much larger dose was required to obtain the same effect.

proton hopping

Short "hops" of protons between a series of hydrogen bonded water molecules effect an extremely rapid net movement of a proton over a long distance. As a hydronium ion gives up a proton, a water molecule some distance away acquires one, becoming a hydronium ion. Proton hopping is much faster than true diffusion and explains the remarkably high ionic mobility of H ions compared with other monovalent cations such as Na or K.

catabolism

Some pathways degrade organic nutrients into simple end products in order to extract chemical energy and convert it into a form useful to the cell antonym: anabolism

sickle cell

The altered properties of hemoglobin S result from a single amino acid substitution, a Val instead of a Glu residue at position 6 in the two chains. The R group of valine has no electric charge, whereas glutamate has a negative charge at pH 7.4. Hemoglobin S therefore has two fewer negative charges than hemoglobin A, one for each of the two chains. Replacement of the Glu residue by Val creates a "sticky" hydrophobic contact point at position 6 of the chain, which is on the outer surface of the molecule. These sticky spots cause deoxyhemoglobin S molecules to associate abnormally with each other, forming the long, fibrous aggregates characteristic of this disorder.

nonpolar gases in water

The molecules of the biologically important gases CO2, O2, and N2 are nonpolar. In O2 and N2, electrons are shared equally by both atoms. In CO2, each C=O bond is polar, but the two dipoles are oppositely directed and cancel each other. The movement of molecules from the disordered gas phase into aqueous solution constrains their motion and the motion of water molecules and therefore represents a decrease in entropy. The nonpolar nature of these gases and the decrease in entropy when they enter solution combine to make them very poorly soluble in water. Some organisms have water-soluble carrier proteins (hemoglobin and myoglobin, bicarbonate for example)

enzyme specificity

The multiplicity of enzymes, their specificity (the ability to discriminate between reactants), and their susceptibility to regulation give cells the capacity to lower activation barriers selectively. This selectivity is crucial for the effective regulation of cellular processes. By allowing specific reactions to proceed at significant rates at particular times, enzymes determine how matter and energy are channeled into cellular activities

citric acid cycle regulation

The overall rate of the citric acid cycle is controlled by the rate of conversion of pyruvate to acetyl-CoA and by the flux through citrate synthase, isocitrate dehydrogenase, and -ketoglutarate dehydrogenase. These fluxes are largely determined by the concentrations of substrates and products: the end products ATP and NADH are inhibitory, and the substrates NAD and ADP are stimulatory. ■ The production of acetyl-CoA for the citric acid cycle by the PDH complex is inhibited allosterically by metabolites that signal a sufficiency of metabolic energy (ATP, acetylCoA, NADH, and fatty acids) and stimulated by metabolites that indicate a reduced energy supply (AMP, NAD, CoA). Isocitrate dehydrogenase is allosterically stimulated by ADP, which signifies the need for more energy. In contrast, NADH and ATP, which signal the presence of high-transfer-potential electrons, inhibit isocitrate dehydrogenase.In addition, a-ketoglutarate dehydrogenase is inhibited by high levels of ATP and NADH. When Isocitrate dehydrogenase inhibits, isocitrate converted to citrate and sent back into the cytoplasm to inhibit PFK. It can then be converted as Acetyl CoA for fatty acid synthesis since there is a surplus of it. Also, a-ketoglutarate is a precursor to some amino acids, so if inhibited it is used for amino acid synthesis.

poison ivy remedy

Wash the area with soap, water, and baking soda (sodium bicarbonate) Soap helps to emulsify and dissolve the hydrophobic alkyl group of an alkyl catechol. Given that the pKa of an alkyl catechol is about 8, in a mildly alkaline solution of bicarbonate (NaHCO3) its OOH group ionizes, making the compound much more water-soluble

release of ordered water favors enzyme-substrate complex

While separate, both enzyme and substrate force neighboring water molecules into an ordered shell. Binding of substrate to enzyme releases some of the ordered water, and the resulting increase in entropy provides a thermodynamic push toward formation of the enzyme-substrate comple

Aspirin, a weak acid with a 3.5 pKa, is absorbed into the blood through the cells lining the stomach and the small intestine. The pH of the stomach contents is about 1.5, and the pH of the contents of the small intestine is about 6. Is more aspirin absorbed into the bloodstream from the stomach or from the small intestine?

With a pKa of 3.5, aspirin is in its protonated (neutral) form at pH below 2.5. At higher pH, it becomes increasingly deprotonated (anionic). Thus, aspirin is better absorbed in the more acidic environment of the stomach, b/c Absorption requires passage through the plasma membrane, the rate of which is determined by the polarity of the molecule: charged and highly polar molecules pass slowly, whereas neutral hydrophobic ones pass rapidly.

zwitterion

a chemical compound whose net charge is zero and hence is electrically neutral. But there are some positive and negative charges in it, due to the formal charge, owing to the partial charges of its constituent atoms.

an enzyme catalyzes a reaction by providing a more comfortable fit for the transition state

a surface that complements the transition state in stereochemistry, polarity, and charge. The binding of enzyme to the transition state is exergonic, and the energy released by this binding reduces the activation energy for the reaction and greatly increases the reaction rate

heterotropic allosteric modulation

describing an allosteric effect in which interaction occurs between nonidentical ligands; the effect may be either cooperative or antagonistic. The term is applied also to such an interaction, to an allosteric enzyme for which different substances act as the substrate and the effector, to the regulation of such an allosteric system, etc.

compounds that make the best buffers

have the pKa closest to desired pH

hydrophobic

hydrophobic—they are unable to undergo energetically favorable interactions with water molecules, and they interfere with the hydrogen bonding among water molecules. Hydrophobic solutes, however, offer no solute-water compensation -results in a small gain of enthalpy; the breaking of hydrogen bonds between water molecules takes up energy from the system Water molecules in the immediate vicinity of a nonpolar solute are constrained in their possible orientations as they form a highly ordered cagelike shell around each solute molecule: the ordering of water molecules reduces entropy. The number of ordered water molecules, and therefore the magnitude of the entropy decrease, is proportional to the surface area of the hydrophobic solute enclosed within the cage of water molecules

solutes alter colligative properties of water by

lowering the effective concentration of water

(2) pH of a STRONG BASED solution of 7.0 x 10^-5M NaOH

pOH = 14 - pH pOH = -logOH pH= 14 + -logOH pH = 14 + -log[7.0 x 10^-5M NaOH]

The strength of hydrophobic interactions

results from the system's achieving greatest thermodynamic stability by minimizing the number of ordered water molecules required to surround hydrophobic portions of the solute molecules

A large Keq

the reaction tends to proceed until the reactants have been almost completely converted into the products