The Quizzes about Acid-Base Equilibria, Amino Acids, and Protein Structure (27 tests)

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A 2-day-old African American boy becomes lethargic and uninterested in breast-feeding. Physical examination reveals hypotonia (low muscle tone), muscle twitching that suggests seizures, and tachypnea (rapid breathing). The child has a normal heartbeat and breath sounds with no indication of cardiorespiratory disease. Initial blood chemistry values include normal glucose, sodium, potassium, chloride, and bicarbonate (HCO3-) levels; initial blood gas values reveal a pH of 7.53, partial pressure of oxygen (PO2) normal at 103 mm Hg, and partial pressure of carbon dioxide (PCO2) decreased at 27 mm Hg. Which of the following treatment strategies is most appropriate?

A 2-day-old Caucasian boy develops tachypnea and cyanosis with a blood pH of 7.1. A serum bicarbonate (HCO3-) is measured as 12 mM, but the (PO2) and (PCO2) are not yet available. Recall the pKa of 6.1 for carbonic acid (reflecting the HCO3-/CO2 equilibrium in blood) and the fact that the blood CO2 concentration is equal to the PCO2 in mm Hg (normal value = 40 mm Hg) multiplied by 0.03. Which of the following treatment strategies is most appropriate?

A 1-year-old Caucasian girl has had frequent wet diapers and seems to always want her bottle or cup. Her pediatrician is concerned about her growth at her 1-year well visit and notes that she had two prior hospitalizations for dehydration. The pediatrician suspects nephrogenic diabetes insipidus (MIM*125800) and orders serum electrolytes that show concentrations of sodium at 155 mEq/L (normal 133-146) and chloride at 123 (normal 98-107). Urinalysis shows a very dilute urine. Further testing involves a gene named aquaporin-2 that has several transmembrane domains demarcated by β turns. Which of the following β-turn amino acids are most likely to be mutated in patients with nephrogenic diabetes insipidus?

A β-turn structure consists of four amino acids in which the first residue is hydrogen bonded to the fourth residue of the turn. Glycine residues are small and flexible, while proline residues assume a cis or flattened conformation, making these residues amenable to tight turns as opposed to the other amino acids listed (incorrect answers a-c and e). Transport proteins often have several membrane-spanning domains demarcated by β turns that allow them to exit and return back into the membrane. These transmembrane domains form channels that regulate transport of ions and water in organs like lung, gut, and kidney. Nephrogenic diabetes insipidus results when the kidney is less responsive to antidiuretic hormone excreted by the posterior pituitary, causing abnormal water excretion, dehydration, and electrolyte disturbances. Treatment is difficult and in part utilizes the paradoxical effect of some diuretics (eg, chlorothiazide or Diuril) in restoring sodium balance.

A 14-year-old Hispanic adolescent presents with acute abdominal pain and is noted to have mildly yellow whites of the eyes (scleral icterus). Blood counts indicate a low hemoglobin concentration and the blood smear shows sphere-shaped instead of biconcave red blood cells. The girl’s mother reports that she, her father, and several other relatives have anemia, and that they have been diagnosed with a form of spherocytosis (MIM*182900) that is caused by mutations in the ankyrin structural protein of erythrocytes. The student on the case is asked to prepare discussion of clinical-molecular correlation on morning rounds, and downloads a diagram of ankyrin structure and amino acid sequence. The structure has domains of antiparallel α helices, which facilitate stacking of ankyrins into ordered arrays. As the student attempts correlation of ankyrin sequence and structure, α-helical domains could be best identified by the absence of which of the following amino acids?

A stable α helix requires hydrogen bonding between peptide bonds at four amino acid intervals. Proline is uncommon in α helices because it destabilizes the helix by introducing a kink that will not form a hydrogen bond with other residues; proline is common in β turns while the other amino acids listed are common in α-helical regions (incorrect answers a-c, e). other residues with negative (glutamates, aspartates) or positive (lysine, arginine) charges will also destabilize the helix if present in large blocks. Ankyrin and spectrin mutations that cause spherocytosis disrupt the α-helical domains and interfere with ankyrin stacking that contributes to red cell shape. The altered shape reduces red cell survival, increases hemolysis, and increases the amount of heme converted to bilirubin. Increased bilirubin may be seen in the whites of the eyes (sclerae) or skin as a yellow color (jaundice). Increased storage of bilirubin in the gall bladder may cause gall stones and inflammation (cholecystitis), leading to acute abdominal pain and sometimes requiring gall bladder removal (cholecystectomy).

A 1-year-old Caucasian girl presents to a pediatrician after being removed from her parents because of severe neglect. The pediatrician notes the child is undersized with tissue and muscle wasting, loss of adipose tissue, mild acidosis, and a hopeless, depressed look. Malnutrition is recognized and supported with laboratory studies that include a low serum protein concentration. The pediatrician institutes a gradual regimen of increased calories and nutrition, gradual because rapid feeding will produce diarrhea, worsening edema, and further protein loss. The extra tissue fluid (edema) and acidosis demonstrate the importance of proteins in maintaining tissue hydration and pH. Indicate the child’s disease and which protein amino acids would have the greatest buffering capacity at physiologic pH.

Proteins can be effective buffers of body and intracellular fluids, evidenced by frequent acidosis and edema with protein malnutrition. This child with emaciation is typical of marasmus (from Greek for consume or exhaust) that is more common with infantile protein deficiency. Kwashiorkor is more common in children over 1 to 2 years, showing edema of the feet, large and fatty liver, reddish hair, and skin depigmentation. Buffering capacity is dependent on the presence of amino acids having ionizable side chains with pKas near physiologic pH. In the example given, only histidine has an ionizable imidazolium group that has a pK close to neutrality (pK = 6.0). Valine and leucine (incorrect answers d, e) are amino acids with uncharged, branched side chains while lysine (incorrect answer a) has a basic amino group (pK = 10.5) and aspartic acid (incorrect answer c) has a side chain carboxyl (pK = 3.8) that is negative at pH 7.


A 60-year-old Caucasian male is brought to his physician from an institution for severe mental deficiency. The physician reviews his family history and finds he has an older sister in the same institution. Their parents are deceased but reportedly had normal intelligence and no chronic diseases. The man sits in an odd position as though he was sewing, prompting the physician to obtain a ferric chloride test on the man’s urine. This test turns color with aromatic (ring) compounds, including certain amino acids, and a green color confirms the physician’s diagnosis. Which of the following amino acids was most likely detected in the man’s urine?

Phenylalanine, with its benzene ring, is an essential amino acid that is converted to tyrosine by phenylhydroxylase, the enzyme (or its cofactor biopterin) that is deficient in phenylketonuria (PKU—MIM*261600). The other amino acid choices (incorrect answers a-c and e) do not have aromatic (benzene ring) side chains—serine has a hydroxyl group, glutamine an amino group, and methionine a sulfhydryl group. Deficiency of phenylalanine hydroxylase in PKU causes elevated substrate (phenyl-alanine) and deficient product (tyrosine), leading to developmental delays and ultimately severe mental retardation if the disease is not recognized. Now children with PKU are detected by newborn screening and placed on low-phenylalanine diets that allow normal brain development. Adults can moderate the greatly restricted and not very tasty diet but may elect to go back on for clear thinking before exams or, in the case of affected females, to prevent birth defects caused by high maternal phenylalanine in pregnancy.

A 2-year-old Caucasian boy is admitted for failure to gain weight. His hair has turned reddish brown and his extremities are swollen with extra subcutaneous fluid water (edema). Initial studies show a serum albumin of 1.5 g/dL (normal for age 3.3-5.8) and total protein 2.7 g/dL (normal for age 5.3-8.1). Which of the following statements best explains the reason for the child’s edema?

Water is an ideal solvent because of its dipole nature (+H2O-), forming hydrogen bonds and solvating positive (eg, arginine-NH4+) and negative (eg, glutamate–COO-) groups of proteins. No covalent bonds or protein aggregates are formed (incorrect answers a, e). The solvated proteins exert osmotic pressure of about 25 mm within vessels, causing net return of fluid in veins (outward hydrostatic pressure 17 mm) and outward fluid flow in arterioles (outward hydrostatic pressure 37 mm). Hydrophobic amino acids (valine, leucine) resist hydration and cluster internally in proteins while hydrophilic (charged) amino acids (glutamate, aspartate) tend to be on the protein surface (incorrect answers c, d). Nonionic but polar compounds are dissolved in water because of hydrogen bonding between water molecules and groups such as alcohols, aldehydes, and ketones.

A 2-year-old Caucasian girl presents with severe vomiting, dehydration, and fever. Initial blood studies show acidosis with a low bicarbonate and an anion gap (the sum of sodium plus potassium minus chloride plus bicarbonate is 40 and larger than the normal 12 ± 2). Preliminary results from the blood amino acid screen show two elevated amino acids, both with nonpolar side chains. A titration curve performed on one of the elevated species shows two ionizable groups with approximate pKs of 2 and 9.5. Which of the following pairs of elevated amino acids is most likely elevated?

Leucine and isoleucine have nonpolar methyl groups as side chains. As for any amino acid, titration curves obtained by noting the change in pH over the range of 1 to 14 would show a pK of about 2 for the primary carboxyl group and about 9.5 for the primary amino group; there would be no additional pK for an ionizable side chain. Recall that the pK is the point of maximal buffering capacity when the amounts of charged and uncharged species are equal. Aspartic and glutamic acids (second carboxyl group), histidine (imino group), and glutamine (second amino group) all have ionizable side chains that would give an additional pK on the titration curve. The likely diagnosis here is maple syrup urine disease, which involves elevated isoleucine, leucine, and valine together with their ketoacid derivatives. The ketoacid derivatives cause the acidosis, and the fever suggests that the metabolic imbalance was worsened by an infection.

Blood is drawn from a 21-year-old African American female with severe anemia and the globin protein is degraded for peptide and amino acid analysis. Of the results below, which change in globin primary structure is most likely to correlate with the clinical phenotype of anemia?

Primary protein structures denote the sequence of amino acids held together by peptide bonds (carboxyl groups joined to amino groups to form amide bonds). The types of amino acids then determine the secondary structure of peptide regions within the protein, sometimes forming spiral α1 helices or flat pleated sheets. These regional peptide secondary structures then determine the overall three-dimensional tertiary structure of a protein, which is vital for its function. Amino acid substitutions that alter the charge of an amino acid side chain, like the change from glutamic acid (charged carboxyl group) to valine (nonpolar methyl groups) in choice b, are most likely to change the secondary and tertiary protein structure. A change in globin structure can cause instability, decreased mean cellular hemoglobin concentration (MCHC), and anemia. A change from glutamic acid to valine at position six in the β- globin chain is the mutation responsible for sickle cell anemia (MIM*602903).

A 35-year-old female with heavy menstrual periods (metrorrhagia) has anemia but does not respond to iron supplementation. Blood is drawn and the red cell hemoglobin is analyzed. Which of the following results is most likely if the patient has an altered hemoglobin molecule (hemoglobinopathy)?

In the technique of polyacrylamide gel electrophoresis (PAGE), the distance that a protein is moved by an electrical current is proportional to its charge and inversely proportional to its size. Patients with normal hemoglobin A have two α-globin and two β1-globin chains, each encoded by a pair of normal globin alleles. Mutation in one α- or β-globin allele alters the primary amino acid sequence of the encoded globin peptide. If the amino acid change alters the charge of the peptide, then the hemoglobin tetramer assembled with the mutant globin peptide has a different charge and electrophoretic migration than the normal hemoglobin tetramer. The electrophoresis of native (undenatured) hemoglobin therefore produces two species (two bands) rather than one, each retaining its heme molecule and red color. If the hemoglobins were first denatured into their α- and β-globin chains as with SDS-polyacrylamide gel electrophoresis, then the similar size of the α- or β-globin peptides would cause them to move closely together as two colorless bands. Identification of these peptides as globin would require use of labeled antibody specific for globin (Western blotting). Because the sodium dodecyl sulfate (SDS) detergent covers the protein surface and causes all proteins to be negatively charged, the distance migrated is solely dependent (inversely proportional) on protein size. High-performance liquid chromatography (HPLC) uses ionic resins to separate proteins by charge. The columns are run under high pressure, rapidly producing a series of proteins that are separated from most negative to most positive (or vice versa, depending on the charge of the ionic resin). A mutant hemoglobin with altered charge should produce a second red protein in the pattern. In dialysis, semipermeable membranes allow smaller proteins to diffuse into the outer fluid, but not larger proteins such as hemoglobin.


A 2-year-old Caucasian girl is brought for evaluation after being found neglected in a trailer with no kitchen facilities. She has extreme irritability due to thin and bleeding gums with tender forearms and lower legs. A diagnosis of scurvy is made among other deficiencies and her vitamin C levels are low. Which of the following amino acids will be deficient in her bone proteins?

Proline and lysine residues in collagen are modified by hydroxylation in a reaction requiring the reducing agent ascorbic acid (vitamin C—eliminating answers a-d). The enzymes catalyzing the reactions are prolyl hydroxylase and lysyl hydroxylase. In scurvy, which results from a deficiency of vitamin C, insufficient hydroxylation of collagen causes abnormal collagen fibrils. The weakened collagen in teeth, bone, and blood vessels causes tooth loss, brittle bones with fractures, and bleeding tendencies with bruising and bleeding gums.

A newborn African American girl has a large and distorted cranium, short and deformed limbs, and very blue scleras (whites of the eyes). Radiographs demonstrate multiple limb fractures and suggest a diagnosis of osteogenesis imperfecta (brittle bone disease—MIM*155210). Analysis of type I collagen protein, a triple helix formed from two α1-collagen and one α2-collagen chains, shows a 50% reduction in the amount of type I collagen in the baby’s skin. DNA analysis demonstrates the presence of two normal α1-alleles and one normal α2-allele. These results are best explained by which of the following?

Collagen peptides assemble into helical tertiary structures that form quaternary triple helices. The triple helices in turn assemble end to end to form collagen fibrils that are essential for connective tissue strength. Over 15 types of collagen contribute to the connective tissue of various organs, including the contribution of type I collagen to eyes, bones, and skin. The fact that only one of two α2-alleles is normal in this case implies that a mutant α2-allele could be responsible for the disease (even if the α2-locus is on the X chromosome, since the baby is a girl with two X chromosomes). The mutant α2-collagen peptide would be incorporated into half of the type I collagen triple helices, causing a 50% reduction in normal type I collagen. (A mutant α1-collagen peptide would distort 75% of the molecules because two α1-peptides go into each triple helix.) The ability of one abnormal collagen peptide allele to alter triple helix structure with subsequent degradation is well documented and colorfully named protein suicide or, more properly, a dominant-negative mutation.

A 12-year-old African American girl, who has tall stature, loose joints, and detached retinas, is found to have a mutation in type II collagen. Recall that collagen consists of a repeating tripeptide motif where the first amino acid of each tripeptide is the same. Which of the following amino acids is the recurring amino acid most likely to be altered in mutations that distort collagen molecules?

The primary structure of collagen peptides consists of repeating tripeptides with a gly-X-Y motif, where gly is glycine and X and Y are any amino acid. The small CH2 group connecting the amino and carboxyl groups of glycine contrasts with the larger connecting groups and side chains of other amino acids. The small volume of glycine molecules is crucial for the α-helix secondary structure of collagen peptides. This in turn is necessary for their tertiary helical structure and their assembly into quaternary tripeptide, triple-helix structures. The most severe clinical phenotypes caused by amino acid substitutions in collagen peptides are those affecting glycine that prevent a helix formation. The child has a disorder called Stickler syndrome (MIM*108300) that exhibits autosomal dominant inheritance.

Children with urea cycle disorders present with elevated serum ammonia and consequent neurologic symptoms including altered respiration, lethargy, and coma. Several amino acids are intermediates of the urea cycle, having side ammonia groups that join with free carbon dioxide and ammonia to produce net excretion of ammonia as urea (NH2CONH2). Which of the following amino acids has an ammonia group in its side chain and is thus likely to be an intermediate of the urea cycle?

Arginine is an amino acid used in proteins that is also part of the urea cycle. Citrulline and ornithine are amino acids not used in proteins but important as urea cycle intermediates. Aspartate is condensed with citrulline to form argininosuccinate in the urea cycle, and acetylglutamate is a cofactor in the joining of carbon dioxide with ammonia to form carbamoyl phosphate at the beginning of the urea cycle.

A child who was normal at birth shows developmental delay with coarsened facial features and enlarged liver and spleen by age 1 year. He is suspected of having Icell disease (inclusion-cell disease—MIM*252500), a lysosomal storage disease with progressive accumulation of complex carbohydrates and glycoproteins in organs. Affected individuals lack multiple enzymes in their lysosomes (with excess amounts in serum) because man-nose 6-phosphate groups that target enzymes to ly sosomes are not correctly synthesized. Which of the following techniques for purification of proteins could be used to isolate the putative lysosomal membrane protein that recognizes mannose 6-phosphate groups and transports enzymes into lysosomes?

Each of the techniques listed separates proteins from each other and from other biologic molecules based on characteristics such as size, solubility, and charge. However, only affinity chromatography can use the high affinity of proteins for specific chemical groups or the specificity of immobilized antibodies for unique proteins. In affinity chromatography, a specific compound that binds to the desired protein— such as an antibody, a polypeptide receptor, or a substrate—is covalently bound to the column material. A mixture of proteins is added to the column under conditions ideal for binding the protein desired, and the column is then washed with buffer to remove unbound proteins. The protein is eluted either by adding a high concentration of the original binding material or by making the conditions unfavorable for binding (eg, changing the pH). The other techniques are less specific than affinity binding for isolating proteins. Dialysis separates large proteins from small molecules. Ion exchange chromatography separates proteins with an overall charge of one sort from proteins with an opposite charge (eg, negative from positive). Gel filtration chromatography separates on the basis of size. Electrophoresis separates proteins on the principle that net charge influences the rate of migration in an electric field. Inclusion-cell disease (mucolipidosis II—MIM*252500) can result from deficiency in either of two phosphotransferase enzymes that put mannose 6-phosphate groups on degradative enzymes, targeting them to lysosomes. Mucolipidosis II with multiple mistargeted enzymes is thus similar to but more severe than disorders like Hunter syndrome (iduronate sulfatase deficiency—MIM*309900) that result from deficiency of a single lysosomal enzyme.


An adolescent presents with shortness of breath during exercise and is found to be anemic. A hemoglobin electrophoresis is performed that is depicted in the figure below. The adolescent’s sample is run with controls including normal, sickle trait, and sickle cell anemia hemoglobin samples and serum. The adolescent is determined to have an unknown hemoglobinopathy. Which of the following lanes contains the adolescent’s sample?

Protein electrophoresis is an important laboratory technique for investigating red cell proteins such as hemoglobin or plasma proteins such as the immunoglobulins. The proteins are dissolved in a buffer of low pH where the amino groups of amino acid side chains are positively charged, causing most proteins to migrate toward the negative electrode (anode). Red cell hemolysates are used for hemoglobin electrophoresis, plasma (blood supernatant with unhemolyzed red cells removed) for plasma proteins. Serum (blood supernatant after clotting) would not contain red cells but would contain many blood enzymes and proteins. In sickle cell anemia, the hemoglobin S contains a valine substitution for the glutamic acid at position six in hemoglobin A. Hemoglobin S thus loses two negative charges (loss of a glutamic acid carboxyl group on each of two β-globin chains) compared to hemoglobin A. Hemoglobin S is thus more positively charged and migrates more rapidly toward the anode than hemoglobin A (figure below Question 19). Lane B must represent the heterozygote with sickle cell trait (hemoglobins S and A), establishing lane A as the normal and lane D as the sickle cell anemia sample. The hemoglobin in lane C migrates differently from normal and hemoglobin S, as would befit an abnormal hemoglobin that is different from S. Lane E must be serum, which does not contain red blood cells.

Which of the following proteolytic enzymes is activated by acid hydrolysis of the proenzyme form?

Pepsin is secreted in a proenzyme form in the stomach. Unlike the majority of proenzymes, it is not activated by protease hydrolysis. Instead, spontaneous acid hydrolysis at pH 2 or lower converts pepsinogen to pepsin. Hydrochloric acid secreted by the stomach lining creates the acid environment. All the enzymes secreted by the pancreas are activated at the same time upon entrance into the duodenum. This is accomplished by trypsin hydrolysis of the inactive proenzymes trypsinogen, chymotrypsinogen, procarboxypeptidase, and proelastase. Primer amounts of trypsin are derived from trypsinogen by the action of enteropeptidase secreted by the cells of the duodenum.

A 3-day-old African American female infant was normal at birth but becomes lethargic after several feedings; the medical student describes an unusual smell to the urine but is ignored. Infection (sepsis) is suspected, and blood tests show normal white blood cell counts with a serum pH of 7.0. Electrolytes reveal an anion gap, and evaluation for an inborn error of metabolism shows an abnormal amino acid screen. The report states that branched-chain amino acids are strikingly elevated. Which of the following amino acids does the report refer to?

The carbon next to a carboxyl (C=O) group may be designated as the α-carbon, with subsequent carbons as β, γ, δ, etc. α-Amino acids contain an amino group on their α-carbon, as distinguished from compounds like γ-aminobutyric acid, in which the amino group is two carbons down (γ-carbon). In α-amino acids the amino acid, carboxylic acid, and the side chain or R group are all bound to the central α-carbon, which is thus asymmetric (except when R is hydrogen, as for glycine). Amino acids are classified as acidic, neutral hydrophobic, neutral hydrophilic, or basic, depending on the charge or partial charge on the R group at pH 7. Hydrophobic (water-hating) groups are carbon-hydrogen chains like those of leucine, isoleucine, glycine, or valine. Basic R groups, such as those of lysine and arginine, carry a positive charge at physiologic pH owing to protonated amide groups, whereas acidic R groups, such as glutamic acid, carry a negative charge owing to ionized carboxyl groups. Glycine has no side chain and is neutral at physiologic pH. Leucine, isoleucine, and valine are amino acids with branched side groups, and they share a pathway for degradation that is deficient in children with maple syrup urine disease (MIM*248600). Their amino groups can be removed, but the resulting carboxy-acids accumulate with resulting acidosis, coma, and death unless a diet free of branched-chained amino acids is instituted.

In comparing the secondary structure of proteins, which of the following descriptions applies to both the α-helix and the β-pleated sheet?

Regular arrangements of groups of amino acids located near each other in the linear sequence of a polypeptide are the secondary structure of a protein. The α helix, β sheet, and β bend are the secondary structures usually observed in proteins. In both the α helix and the β sheet, all the peptide bond components participate in hydrogen bonding. That is, the oxygen components of the peptide bond form hydrogen bonds with the amide hydrogens. In the case of the α helix, all hydrogen bonding is intrachain and stabilizes the helix. In the case of β sheets, the bonds are interchain when formed between the polypeptide backbones of separate polypeptide chains and intrachain when the β sheet is formed by a single polypeptide chain folding back on itself. While the spiral of the α helix prevents the chain from being fully extended, the chains of β sheets are almost fully extended and relatively flat. The chains of β sheets can be either parallel or antiparallel. When the N-terminals of chains run together, the chain or segment is considered parallel. In contrast, when N- and Cterminal ends of the chains alternate, the β strand is considered antiparallel.

A 6-year-old African American girl with speech delay is found to have a large, abnormal peak when blood amino acids are measured. The abnormal amino acid migrates toward the anode, indicating a positively charged side group in addition to its carboxyl and amino groups. Which of the following amino acids is most probable and what medical procedure is most important?

Except for terminal amino acids, all α-amino groups and all α-carboxyl groups are utilized in peptide bonds. Thus, only the side chains of amino acids may be ionizable in proteins. Seven of the 20 common amino acids have easily ionizable side chains. Lysine, arginine, and histidine have basic side chains (yielding a positive charge at neutral pH with migration toward the negative anode); aspartate and glutamate have acidic side chains (yielding a negative charge at neutral pH); and tyrosine and cysteine have hydroxyl/sulfhydryl groups (ionizing only at basic pHs or within special environments of protein/enzyme active sites/channels). A hearing test is the first investigation for speech delay, since hearing loss is the most common cause of speech problems. Laryngoscopy would reveal rare causes such as palatal dysfunction or laryngeal clefts, and these would manifest more as disarticulation than delay. Histidinemia (MIM*235800) is one of several abnormalities discovered when advances in ion exchange chromatography and paper electrophoresis made screening of blood and urine amino acids distributions feasible for patients. These diagnostic tests allowed confirmation of clinically defined disorders like phenylketonuria (MIM*261600), and revealed a host of new disorders like histidinemia or hyperprolinemia (MIM*239500). Although the latter disorders have been traced to specific enzyme deficiencies, their clinical significance is uncertain because many individuals with elevated screens do not have disease.


The oxygen carrier of muscle is the globular protein myoglobin. Which of the following amino acids is highly likely to be localized within the interior of the molecule?

The structure of myoglobin is illustrative of most water-soluble proteins. Globular proteins tend to fold into compact configurations with nonpolar cores. The interior of myoglobin is composed almost exclusively of nonpolar, hydrophobic amino acids like valine, leucine, phenylalanine, and methionine. In contrast, polar hydrophilic residues such as arginine, aspartic acid, glutamic acid, and lysine are found mostly on the surface of the water-soluble protein.

A 2-year-old Asian child has stopped progressing in speech and develops coarse facial features with thick mucous drainage. Skeletal deformities including curved spine (kyphosis), thickened and short fingers, and curved limbs appear over the next year, and the child regresses to a vegetative state by age 10 years. The child’s urine tests positive for glycosaminoglycans that include which of the following molecules?

Glycosaminoglycans (mucopolysaccharides) are polysaccharide chains that may be bound to proteins as proteoglycans. Each proteoglycan is a complex molecule with a core protein that is covalently bound to glycosaminoglycans—repeating units of disaccharides. The amino sugars forming the disaccharides contain negatively charged sulfate or carboxylate groups. The primary glycosaminoglycans found in mammals are hyaluronic acid, heparin, heparan sulfate, chondroitin sulfate, and keratan sulfate. Inborn errors of glycosaminoglycan degradation cause neurodegeneration and physical stigmata described by the outmoded term “gargoylism”—exemplified by Hurler syndrome (MIM*252800). Glycogen is a polysaccharide of glucose used for energy storage and has no sulfate groups. Collagen and fibrillin are important proteins in connective tissue. γ-Aminobutyric acid is a γ-amino acid involved in neurotransmission.

Under normal conditions in blood, which of the following amino acid residues of albumin is neutral?

In blood and other solutions at physiologic pH (approximately 7), only terminal carboxyl groups, terminal amino groups, and ionizable side chains of amino acid residues in proteins have charges. The basic amino acids lysine, arginine, and histidine have positive charges (protonated amines). The acidic amino acids aspartate and glutamate have negative charges (ionized carboxyls). Glutamine possesses an uncharged but hydrophilic side chain.

A 20-year-old Caucasian female comes in with her husband for preconception counsel as they have decided to have children. Her gynecologist notices that she has very thin skin with multiple bruises and easy visualization of the underlying veins. Further history discloses joint hypermobility with frequent dislocation, and on physical examination she can appose her thumbs to her forearms, reach an arm behind her back to touch her umbilicus in front, and spontaneously dislocate her shoulder. Further referral and diagnostic DNA testing reveals that the woman has type IV Ehlers-Danlos syndrome (MIIM 130050) due to a mutation in the gene for type III collagen on chromosome 2. She is informed that a pregnancy would likely be lethal due to breakdown of major arteries from stress, and the couple decide to pursue adoption. Which of the statements below best apply to her collagen III gene mutation?

Several diseases (osteogenesis imperfecta, Ehlers-Danlos, Marfan syndrome) result from mutations in collagens, a large family of proteins that are important for connective tissue. Different types of collagens occur in bone, ligaments, joints, sclerae (whites of the eyes), and even the inner ear. Collagen peptides have repeating units of gly-X-Y, allowing them to form triple helices that lend structural support to tissues. Glycine is the most important residue for peptide integrity because of its small size and absent side chain, allowing tight packing of collagen peptides into fibers—a change from glycine to proline would disrupt this packing and lead to severe fragility of vascular tissue as in type IV EDS (MIM*130050). Silent mutations not altering the encoded amino acid would have little effect, with one allele on an autosome likely mutated than two. Heterozygous mutations cause 50% of the “brick” proteins in connective tissue walls to be malformed, accounting for fragility in connective tissue dysplasias and the fact that most exhibit autosomal dominant inheritance.

Which of the following amino acids is aromatic (ring compound), and in a pathway leading to neurotransmitters and melanin?

Amino acids are composed of an α-carbon atom bonded to carboxyl, amino, and side chain R groups. The α-carbon is so named because it is adjacent to the carboxyl group. The distinctive R side chains, with their variation in charge, shape, size, and reactivity, account for the diversity of protein conformations and functions. Aliphatic amino acids contain carbon chains as side groups (eg, leucine, isoleucine, and valine). Aromatic amino acids have rings in their side groups, like phenylalanine and tyrosine. Those with carbon chains or rings are hydrophobic in nature, causing them to sequester together away from water in the interior of proteins. Polar amino acids have ionizable groups on their side chains, including basic amino acids (positively charged at neutral pH—lysine, arginine, histidine) and acidic amino acids (negatively charged at neutral pH—glutamate, aspartate). Polar amino acids are located on the outsides of proteins and moderate interactions of proteins with themselves and smaller molecules. Aromatic rings interact to produce colors, and the benzene ring of tyrosine is incorporated into melanin. Other branches of this pathway produce important neurotransmitters such as catecholamines and dopamine. External amino acids also provide substrates for enzymic modification of protein conformation and function, illustrated by the phosphorylation of tyrosine by kinases.


Which of the following substances is primarily found in tendons?

Collagens are insoluble proteins that have great tensile strength. They are the main fibers composing the connective tissue elements of skin, bone, teeth, tendons, and cartilage. Collagen is composed of tropocollagen, a triple-stranded helical rod rich in glycine, proline, and hydroxyproline residues. Troponin is found in muscle, fibrillin in heart valves, blood vessels, and ligaments (it is defective in Marfan syndrome [MIM*154700]). Fibrin is a component of blood clots and fibronectin is a component of extracellular matrix.

Which of the following is primarily found in the extracellular matrix?

The major macromolecular components of ground substance are proteoglycans, which are made up of polysaccharide chains attached to core proteins. The polysaccharide chains are made up of repeats of negatively charged disaccharide units. This polyanionic quality of proteoglycans allows them to bind water and cations and thus determines the viscoelastic properties of connective tissues. Collagen is the other major component of connective tissue besides ground substance. The cornified layer of epidermis derives its toughness and waterproof nature from keratin. Keratins are disulfide-rich proteins that compose the cytoskeletal elements known as intermediate filaments. Hair and animal horns are also composed of keratin. Troponin is a component of muscle, fibrin of blood clots.

The Quizzes about Acid-Base Equilibria, Amino Acids, and Protein Structure (27 tests)
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