Flashcards in Clinical Correlates 1 Functional Chemistry Deck (30):
HCl is produced by the parietal cells of the stomach. The H+-K+ ATPase (the proton pump) in the cell membrane is responsible for producing as much as 2 L of acidic gastric fluid per day. Some individuals have a condition known as gastroesophageal reflux disease (GERD), which results from reflux of HCl back into the esophagus. This condition creates a burning sensation in the chest, along with cough and even shortness of breath. The proton pump can be inhibited by ??
proton pump inhibitors (PPIs) such as omeprazole.
The carbonic anhydrase inhibitor, ____, blocks the above reaction and is used for the treatment of glaucoma as well as altitude sickness.
The normal pH range of arterial blood is ___.
a. The major buffers of blood are bicarbonate (HCO3
/H2CO3) and hemoglobin (Hb/HHb).
b. These buffers act in conjunction with mechanisms in the kidneys for excreting protons and mechanisms in the lungs for exhaling CO2 to maintain the pH within the
7.37 to 7.43.
___ ___ can result from accumulation of metabolic acids (lactic acid or the ketone bodies, b-hydroxybutyric acid, and acetoacetic acid) or ingestion of acids or compounds that are metabolized to acids (e.g., methanol, ethylene glycol).
Metabolic ____ is due to increased HCO3, which is accompanied by an increased pH. Acid-base disturbances lead to compensatory responses that
attempt to restore normal pH.
For example, a metabolic acidosis causes hyperventilation and the release of CO2, which tends to raise the pH. During metabolic acidosis, the kidneys excrete NH4+, which contains H+ buffered by ammonia:
The glycoside digitalis and its derivatives are of clinical significance because they inhibit the ___ on cell membranes. Such drugs are used in the treatment of congestive heart failure.
The oxidation of glucose by ____ (a highly specific test for glucose) is used by clinical and other laboratories to measure the amount of glucose in
urine using a dipstick.
Glucose forms ___ acid. Conjugation with glucuronic acid makes lipid compounds more water soluble (e.g., bilirubin diglucuronide).
Infants have a decreased ability to conjugate glucuronic acid onto drugs such as chloramphenicol. Administration of this antibiotic during the neonatal period can result in elevated plasma levels of the drug and a fetal shocklike syndrome referred to as ???
gray baby syndrome.
Because dipsticks only detect glucose, many clinical laboratories use a chemical test for ____, a modified Benedict test for reducing sugars, which also will detect the presence of sucrose, galactose, and fructose. Most newborn and infant urine is routinely screened for reducing sugars to detect inborn errors in metabolism.
Glucose is reduced to sorbitol, and galactose to galactitol.
Sorbitol does not readily diffuse out of cells. As it accumulates in cells, it causes osmotic damage to cells of the nervous system, resulting in cataracts and
Glycosylation of proteins: Addition of sugar moieties to proteins can alter proteins in many ways, including modifying their function, protecting them from proteolysis, and directing their intracellular traffic, as well as direct cellular movement.
Patients with leukocyte adhesion deficiency (LAD) II have a congenital deficiency in the ability to glycosylate ligands for cell surface selectins, which mediate immune cell migration. Such patients are prone to recurrent life-threatening infections.
_____ is a glycosaminoglycan, which is an important anticoagulant found in the granules of mast cells. It can be used during the treatment of myocardial infarction as well as for the prevention of deep venous thrombosis during hospitalizations.
The__ ___ infects cells by binding its viral hemagglutinin to sialic acid on the surface of epithelial cells.
____ functions as an inhibitory neurotransmitter in the brainstem and spinal cord. Its actions are antagonized by the rodenticide strychnine, leading to twitching and muscle spasm.
Charges on a-amino and a-carboxyl groups: At physiologic pH, the a-amino group is protonated (pKa 9) and carries a positive charge, and the carboxyl group is dissociated (pKa 2) and carries a negative charge.
Charges on side chains
a. Positive charges are present on the side chains of the basic amino acids arginine, lysine, and histidine at pH 7.
b. Negative charges are present on the side chains of the acidic amino acids aspartate and glutamate at pH 7.
_____ is the amino acid in the highest concentration in the brain and functions as a neurotransmitter in the brain and spinal cord.
____ is an antiglutamatergic drug used for treatment of Alzheimer disease.
____ ____ is implicated in schizophrenia, in which drugs of abuse, like ketamine and phencyclidine, affect glutamate binding to its receptor.
____ toxin binds to the ganglioside GM1 receptor on cells and upon entry causes a potentially life-threatening watery diarrhea.
The cystic fibrosis transmembrane regulator (CFTR) is a ___ found on cell membranes. Mutation in this protein (the most common of which is the loss of a phenylalanine residue at position 508, known as the DF508 mutation) results in cystic fibrosis (CF).
CF is the most common lethal genetic disease in Caucasians and results in _____ of the respiratory tract with recurrent life-threatening pulmonary infections.
chloride ion channel
1. Acetazolamide is a carbonic anhydrase inhibitor and is used in the treatment of all the following conditions except which one?
(D) Altitude sickness
(E) Congestive heart failure
A. Acetazolamide is a potent carbonic anhydrase inhibitor and helps to reduce conditions of volume overload (not volume decrease, which would be brought about by dehydration).
In the eye, carbonic anhydrase inhibitors lead to a decrease in the secretion of aqueous humor, which reduces intraocular pressure. In patients with epilepsy, these inhibitors block the activity of the central nervous system neuron carbonic anhydrase, which decreases excessive neuronal discharge. In the treatment of individuals with altitude sickness, the mechanism of the carbonic anhydrase inhibitor appears to be related to the acid-base effects of the drug. Patients with congestive heart failure take these inhibitors, and the effect of the inhibitors is to act as a diuretic, which helps to manage and reduce intravascular volume.
2. Sickle cell disease results in abnormal hemoglobin formation because of a point mutation in DNA that leads to the insertion of which amino acid into b-globin?
(B) Glutamic acid
E. Sickle cell anemia is caused by a point mutation in DNA, which leads to glutamic acid at position 6 of the b-chain of globin being replaced with the hydrophobic amino acid valine. This mutation of the b-globin gene causes the polymerization of hemoglobin under low oxygen conditions, distorting the red blood cells into an inelastic, sickle shape. The most life threatening manifestations of sickling, or a ‘‘sickle crisis,’’ are aplastic crisis, splenic sequestration, vaso-occlusive crisis, and acute chest syndrome.
3. A 67-year-old man suffers from congestive heart failure. He is taking digoxin, an effective chronotrope and inotrope, which is an ether that contains a sugar component (glycol) and a nonsugar (aglycone) component attached via oxygen. Digoxin would be best classified as which of the following?
B. Digoxin is a medication that can improve the contraction of the heart. It is a drug that has been around for centuries and is made from the foxglove plant. A glycoside is an ether containing a sugar component (glycol) and a nonsugar (aglycone) component attached via oxygen or nitrogen bond; hydrolysis of a glycoside yields one or more sugars. A glycoprotein contains sugars attached via glycosidic linkage to amino acid side chains of the protein. An oligosaccharide is the linkage of a number of sugars in glycosidic bonds. A glucosteroid is a type of steroid hormone. A thioester linkage contains a sulfur bonded to a carbon, which has a carbonyl group also attached to it.
4. Which amino acid is a major neurotransmitter in the brain?
B. Glutamate functions as the most important and abundant excitatory neurotransmitter in the brain. It is released from the presynaptic membrane and interacts with postsynaptic glutamate receptors such as the NMDA (N-methyl-D-aspartate) receptor. Antagonists of NMDA, such as ketamine, are used clinically to provide dissociative anesthesia in children.
5. Influenza virus results in more than 500,000 deaths worldwide annually. Influenza A contains an eight-piece segmented negative-sense RNA genome. Two important proteins encoded by this genome are HA (hemagglutinin) and NA (neuraminidase). The HA protein directly binds to which host cell epithelial component?
(A) Sialic acid
(C) Cytokine receptors
(D) Serine-threonine kinase receptors
(E) Uronic acid subgroups
A. The influenza virus enters the epithelial host cell by binding to sialic acid residues found on the cell surface. Sialic acid is a modified sugar residue. Cerebrosides are glycolipids synthesized from ceramide and a UDP-sugar; a common one is glucocerebroside.
Cytokine receptors (which work through the JAK kinase and STAT transcription factors) and serine-threonine kinase receptors are two types of receptors involved in signal transduction, which is initiated after a chemical messenger (e.g., hormone, neurotransmitter, or cytokine) binds to the receptor on the plasma membrane. Uronic acid is an oxidized sugar and is a component of proteoglycans. Uronic acid is not usually found as a part of glycoproteins, as sialic acid is.
6. A young infant, who was nourished with a synthetic formula, was found to have a serum and urine sugar compound that yielded a positive reducing-sugar test but was negative when measured with glucose oxidase. Treatment of the urine and serum with acid to cleave glycosidic bonds did not increase the amount of reducing sugar measured. Which of the following compounds is most likely to be present in this infant’s urine and serum?
B. Fructose gives a positive result in a reducing-sugar test and a negative result in a glucose oxidase test. Glucose would yield a positive test result with the enzyme glucose oxidase. Sorbitol has no aldehyde or ketone group and, thus, is not a reducing sugar and cannot be oxidized in the reducing-sugar test. Maltose and lactose are disaccharides that undergo acid hydrolysis, which doubles the amount of reducing sugar. Because fructose is a monosaccharide, acid would have no effect on the amount of reducing sugar present.
7. A medical student is assigned to a patient in the intensive care unit. A review of the patient’s medications shows that he is taking a proton pump inhibitor (PPI). This class of drugs inhibits the production of which of the following major acids produced by the body?
(A) Phosphoric acid
(B) Sulfuric acid
(C) Lactic acid
(D) b-Hydroxybutyric acid
(E) Hydrochloric acid
E. The proton pump inhibitors, such as omeprazole, inhibit the H+-K+ ATPase, which is responsible for the production of hydrochloric acid by the gastric parietal cells. Many patients are given these medications in the hospital to prevent the development of gastric ulcers.
8. Proton pump inhibitors are a mainstay in the treatment of peptic ulcer disease and inhibit the gastric hydrogen ATPase. ATPases are in a class of enzymes that catalyze the hydrolysis of a high energy bond in adenosine triphosphate (ATP) to form adenosine diphosphate (ADP) and a free phosphate ion. The hydrogen ATPase in the gastric mucosal parietal cell utilizes this energy to exchange one hydrogen ion from the cytoplasm for one extracellular potassium ion. What type of transport is this enzyme catalyzing?
(A) Antiport coupled transport
(B) Symport coupled transport
(C) Facilitated diffusion
(D) Simple diffusion
A. The action of the gastic hydrogen ATPase is in antiport coupled transport: the exchange between hydrogen for potassium is driven by the energy released by the conversion of ATP to ADP. Symport coupled transport, although a form of active transport as well, results in the passage of molecules together across a membrane, such as the glucose-Na+ cotransporter. Facilitated and simple diffusion are passive mechanisms for the transfer of a molecule across a membrane. The driving force for passive and simple diffusion relies primarily on the concentration gradient of the molecule across the membrane and requires no energy. Facilitated diffusion
uses a carrier protein to transfer the molecule across the membrane, whereas simple diffusion does not require a carrier. Osmosis is the diffusion of a solvent (usually water in biologic systems) across a semipermeable membrane in response to a difference in solute concentration across the membrane.
9. A 76-year-old bedridden nursing home resident begins to develop swelling of her left leg. A venous Doppler ultrasound is ordered and shows an obstructive deep vein thrombosis extending from her left common femoral vein to her popliteal vein with limited blood flow. The patient is immediately started on heparin to further prevent the clot from enlarging. Heparin is an example of which of the following?
D. Heparin is an example of a glycosaminoglycan, a long repeating chain of disaccharide units attached to a core protein. The sugar residues of heparin are sulfated. Cerebrosides and gangliosides are both examples of sphingolipids derived from the lipid ceramide. Prostaglandins are derived from polyunsaturated fatty acids, an example of which is arachidonic acid
10. A 43-year-old alcoholic man has been taking the drug cimetidine for gastric reflux. His primary care physician warns that this is not a good idea given his poor liver function and decreased ability for glucuronidation. Glucuronidation involves the addition of a carbohydrate
molecule that has been derived from glucose, by which of the following mechanisms?
A. Glucuronidation makes the drug more water soluble and, therefore, more easily secreted by the kidneys. Glucuronic acid is derived from glucose via oxidation of the oxygen on carbon 6 of glucose. Sulfated sugars are found in glycosaminoglycans. Reduction of glucose at carbon 1 forms sorbitol, whereas phosphorylation of glucose (usually at position 6) traps glucose within the cell and commits it to metabolism. Mutarotation occurs when a-glucose is converted to b-glucose, a process that requires passage through a straight-chain aldehyde.