Week 1

What enzyme is responsible for removing short fragments of RNA that are base paired to DNA template?

DNA polymerase I removes RNA primers via 5' to 3' exonuclease activity and replaces them with DNA via 5' to 3' polymerase activity.

What enzymes involved in DNA replication have proofreading activity?

DNA polymerases

Certain viruses lose their infectivity after being exposed to ether. What types of viruses are being described? Why does this occur?

Enveloped viruses Ether and other organic solvents dissolve the lipid bilayer of viral envelopes, therefore decreasing viral infectivity.

What is the process of base excision repair

Glycosylase removes altered base and creates AP site, endonuclease removes one or more nucleotides, lyase completes the extraction of the AP site, DNA polymerase beta fills gap and DNA ligase seals it. Occurs throughout cell cycle.

Study: Men are found to have X-linked mutation in PRPP syntetase, resulting in increased substrate conversion. What condition will this lead to? What are the primary cells responsible for the inflammatory response with this condition? What is the treatment of an acute attack of this condition?

Gout Neutrophils NSAIDs first line, colchicine if NSAID can't be taken.

14 month old has failure to thrive and developmental delay. He has decr hb and elevated MCV. Normal ammonia and reticulocytes. Urine shows orotic acid crystals. What is dx? What is inheritance pattern? What enzyme is deficient? What can you supplement to improve sx?

Hereditary orotic aciduria AR uridine 5'-monophosphate (UMP) synthase Uridine, which bypasses enzymatic defect

38 y/o male being treated for AML presents with fevers, lethargy, and now right-sided HAs behind eye and associated with nasal stuffiness. What is dx and causative agent? Who is at risk of getting this condition? Where does this condition most commonly affect? What are the histological characteristics?

Mucormycosis caused by Mucor, Rhizopus, or Absidia Immunocompromised pts are at high risk Affects paranasal sinuses Mold form only. Form broad, nonseptate hyphae that branch at wide (often 90 degree) angles. Treated by surgical debridement and amphotericin B

29 y/o male is positive for HBsAg. What is most likely outcome for his infection?

The most common outcome for HBV-infected adults is acute hepatitis with mild sx that eventually completely resolves.

Experiment: 2 growth media with erythropoeitin, one folate deficient and the other supplemented with folic acid (control). Cells proliferate in control and differentiate into reticulocytes; minimal cell division in folate-deficient media with cells undergoing apoptosis. A substance is then added to the non-control that prevents apoptosis and permits proliferation. What substance is this? How does the substance work in this case?

Thymidine Normally thymidylate synthase converts dUMP to dTMP. In the experiment, low folate inhibits the enzyme. Thymidine inhibits the apoptosis.

What are the enzymes involved in the nonoxidative (reversible) part of the pentose phosphate pathway? What do they do?

Transketolase: interconverts Ribose-5-phosphate and glyceraldehdye-3-phosphate Transaldolase: Interconverts Fructose-6-phosphate and glyceraldehyde-3-phosphate

What two mechanisms regulate the lac operon? What will a mutation impairing the binding of the repressor protein to its beinding site do?

1. Negative regulation by binding of repressor protein to operator locus 2. Positively by cAMP-CAP binding upstream from the promoter region Mutations impairing the binding of the repressor protein prevent repression of the genes of the lac operon in the absence of lactose. This leads to constitutive expression of the structural genes of the lac operon.

How long before the body's glycogen stores are depleted? What happens once glycogen stores are depleted? What does the body produce to conserve protein? What tissue cannot use this energy source as fuel and why?

12-18 hours of fasting before glycogen stores are depleted. Gluconeogenesis then maintains blood glucose levels. After a while, the body limits its reliance on gluconeogenesis in an effort to conserve protein and resorts to ketone body synthesis. Erythrocytes cannot use ketone bodies as a fuel source because they lack mitochondria.

74 y/o woman has DVT and embolectomy is performed. Several hours later the pt begins to experience severe calf pain on same side. What is dx and MOA?

Acute compartment syndrome secondary to reperfusion injury. Molecular O2 reacts with xanthine oxidase, NADPH oxidase, and NO synthase to form ROS such as superoxide, hydroxyl radicals and singlet oxygen. Antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase, convert ROS to oxygen and water, neutralizing their capacity for cellular damage.

22 y/o w/ 5-day hx of nausea, constipation, poorly localized abd pain, anxiety, decr concetration, poor sleep quality, and tingling of limbs. She has had similar episodes in the past. She is on a restrictive diet to lose weight. Her sx improve rapidly after IV infusion of heme preparation. What is the dx? What is the affected enzyme? What substrates accumulate? What is treatment? What can cause attacks?

Acute intermittent porphyria Porphobilinogen deaminase Porphobilinogen and ALA Glucose and heme, which inhibit ALA synthase Drugs (P450 inducers), alcohol, starvation

68 y/o male w/ hx of atherosclerotic CVD and CABG presents with abd pain and nausea. Exam shows diffuse tenderness and decr BS. Labs show decreased bicarb, low pH, lo PaCo2, elevated lactic acid. ECG shows absent P waves and irr rate and rhythm. CT abd shows colonic wall thickening and no IV contrast enhancement. What is dx? What renal process does the acid-base d/o cause?

Acute ischemic colitis 2/2 embolic dz Renal ammoniagenesis: Renal epithelial cells metabolize glutamine, generating ammonium and bicarb. Ammonium ions are transported into the tubular fluid and excreted in the urine while peritubular capillaries absorb bicarb, which buffers acid in the blood.

64 y/o male with PMH of HTN, MI, and heart failure presents with abd pain, nausea, and vomiting. He has low BP, tachycardia, and tachypnea. Abdomen is distended and tender. ABG shows acidosis. What is dx? What would CT findings be? Which enzyme's activity is decreased and why?

Acute mesenteric ischemia Ileal wall thickening, lack of enhancement with IV contrast Pyruvate DH; Underhypoxic conditions, intracellular accumulation of NADH inhibits pyruvate DH. Increased amounts of pyruvate are converted to lactate. This leads to lactic acidosis.

Before alanine is converted to glucose, its amino group is transferred to what molecule? Where does the alanine come from? What is its primary function?

Alanine transfers its amino group to a-ketoglutarate which forms glutamate, which is then processed in the liver to form urea, the primary disposal form of nitrogen in humans. Alanine can be formed from glutamine, which is produced by most body tissues. Alanine is also released by skeletal muscle tissue during protein catabolism as part of the glucose-alanine cycle that helps remove excess nitrogen. Alanine is the major AA responsible for transferring nitrogen to the liver for disposal.

2 y/o well-developed boy is toilet-training. Forgets to flush toilet at night and in the morning urine is black. UA is normal besides black color. What is the dx? What enzyme is deficient and what is its normal function? What pathway is involved? What is responsible for the black urine? Inheritance pattern of this condition?

Alkoptonuria Homogentisic acid dioxygenase, converts homogentisate to maleylacetoacetate Conversion of tyrosine to fumarate Homogentisic acid accumulation, which imparts black color to urine if it sits and is oxidized. AR

24 y/o eats wild mushrooms and develops abdominal pain, vomiting, and watery diarrhea. On exam he is ill-appearing and jaundice with an enlarged and tender liver. ALT, AST, and bilirubin are elevated. No PMH or meds. What is the dx? What is inhibited by the responsible toxin? How does the toxin work?

Amatoxin poisoning mRNA synthesis Amatoxins bind to DNA-dependent RNA polymerase type II and halt mRNA synthesis, resulting in apoptosis.

34 y/o male w/ HIV presents with pain and itching in perirectal area. Found to have a mass with superficial ulceration in anal canal. What is dx? What pathogen is most likely responsible for this pathology?

Anal squamous cell carcinoma HPV

54 y/o female presents with dyspnea and fatigability. No CP, cough, wheezing. no T/A/D. Pt has unstable gait with closed eyes, and there is impaired vibratory sensation in BLE. There is pallor of conjunctiva, nails, and palms. What does the pt have? What is the deficient substance a cofactor for?

Anemia with B12 deficiency Methylmalonyl-CoA mutase (converts methylmalonyl-CoA to succinyl-CoA) and methionine synthase (converts homocysteine and folic acid to methionine).

What serological marker will be positive in someone who is vaccinated against HBV? What serological markers will be present in someone who have recovered from HBV?

Anti-HBs Anti-HBs and anti-HBc

A 14 y/o female with sickle cell disease presents with rapidly progressive exertional dyspnea and generalized weakness, which were preceded by a mild febrile illness several days ago. Hematocrit is 16% and reticulocyte count is low. What is the dx? What is the most common causative pathogen and its characteristics. What is the MOA?

Aplastic crisis Causes by parvovirus B19 in sickle cell patients. It is a naked, linear ss DNA virus. Parvovirus B19 destroys erythroid precursor cells

36 y/o man with yellow skin nodules on palms, elbows, knees, buttocks increasing in size and number. Father died of MI at 56 y/o. Biopy of lesion shows lipid laden macrophages. What proteins are defective? What are the proteins responsible for? What is underlying condition? What is the name of the yellow nodules?

ApoE proteins ApoE proteins are found on chylomicrons and VLDLs and are responsible for binding apolipoprotein receptors so that the liver can remove chylomicrons and VLDL remnants from circulation. Familial dysbetalipoproteinemia (type III hyperlipoproteinemia) Xanthoma

3 y/o boy with motor development abnormality. Was normal during first year, but for past two years has had BLE stiffness and involuntary movements. Also has cognitive and motor development delays. Height, weight, and head circumference below 3rd percentile. Labs show elevated arginine in plasma and CSF. What is deficient in this pt? What is the normal function of the deficient substance? What is treatment for condition? What sx are characteristic of this condition?

Arginase Usually produces urea and ornithine from arginine Low protein diet devoid of arginine, admin of synthetic protein made of essential amino acids. Spastic diplegia, growth delay, abnormal movements

34 y/o male presents with fever, chills, SOB, and AMS. He had abdominal trauma 2 years ago during which laparotomy was performed. BP is high and HR is high. What is current condition? What predisposed pt to current condition? What is pt susceptible for?

Asplenic sepsis Lack of spleen prevents clearance of circulating bacteria. The spleen acts as both a blood filter that can remove circulating pathogens and as a major site of opsonization. Pt susceptible infections caused by encapsulated organisms such as S pneumoniae, H influenzae, and N meningitidis

53 y/o male presents with 2 weeks of low-grade fevers and fatigue. There is an early diastolic murmur present and subungual hemorrhages. Labs show leukocytosis and elevated ESR. What is dx and offending organism? What type of organism is this and where is it normally found? How does this organism contribute to the pt's cardiac sx?

Bacterial endocarditis caused by viridans streptococci These are gram +, alpha-hemolytic cocci normal found in the oropharynx and cause dental caries They can produce insoluble extracellular polysaccharides (dextrans) using sucrose as a substrate which aid them in colonizing host surfaces (i.e. dental enamel and heart valves)

31 y/o male has been consuming large amounts of raw egg whites. What deficiency is he at risk for? What is the function of this potentially deficient substance? What are manifestations of this deficiency?

Biotin Serves as a cofactor for carboxylation enzymes Sx include dermatitis, alopecia, enteritis

13 y/o boy with growth retardation, microcephaly, sun-sensitive skin rash, and recurrent infections has a mutation in BLM gene. What is dx and inheritance pattern? What enzyme is deficient? What is the function of the enzyme?

Bloom syndrome, AR Helicase deficiency Helicase binds to ssDNA at origin of replication and moves into the replication fork, separating and unwinding the dsDNA.

Describe reason for difference in clinical severity between HbC and HbS.

Both involve substitutions at position 6. HbS: acidic glu is replased by nonpolar valine (neutral), which forms hydrophobic pocket that interacts with nonpolar residues on other hemoglobin molecules which leads to polymerization and sickling. HbC: acidic glu is replaced by basic polar lysine (+). There is no hydrophobit interaction and no polymerization/sickling.

A baby has torticollis. An injection is given that temporarily relieves the spasms. What is this injection composed of? What is the MOA of the agent? What are the characteristics of the agent?

C botulinum Produces heat labile toxin that inhibits ACh release at the NMJ. Gram positive, spore-forming, obligate anaerobic rod

56 y/o male with 3 months of fatigue and dyspnea, also has early satiety and upper abd discomfort. He has splenomegaly but no lymphadenopathy. He has low Hb, low plts, and high leukocytes. What is dx? What is the cause? What would RT-PCR detect in this pt?

CML Translocation that causes BCR gene on chromosome 22 to fuse with ABL gene on chromosome 9, forming BCR-ABL fusion gene. mRNA transcript with BCR and ABL exons. RT-PCR detects and quantifies levels of mRNA.

56 y/o male with a history of diabetes, HTN, and gout presents with progressive visual impairment. Physical examination shows bilat clouding of lens. What is the dx? What metabolic conversion is responsible for the condition and what enzyme is involved? How is this pathway affected by pt's PMH? What is the physiologic affect of the accumulated substrate?

Cataracts Glucose to sorbitol; aldose reductase Aldose reductase converts glc to sorbitol, then sorbitol dehydrogenase oxidizes sorbitol to fructose. In hyperglycemia, sorbitol is formed faster than its metabolism to fructose and it accumulates. Sorbitol increases osmotic pressure and stimulates influx of water, leading to osmotic cellular injury.

Wha are the most common causes of PID? Characteristics of PID? Complications of PID?

Chlamydia trachomatis, N. gonorrhea Cervical motion tenderness, purulent cervical discharge, salpingitis, endometritis, hydrosalpinx, tubo-ovarian abscess. Complications include ectopic pregnancy, infertility, chronic pelvic pain, Fitz-Hugh-Curtis syyndrome (infection of liver capsule and "violin sting" adhesions of peritoneum to liver.

Fibroblasts synthesize polypeptide chains that assemble into triple helical structures, followed by fibrils. What are these proteins? Which AA is most likely to be found in highest quantity in these proteins?

Collagen Glycine, which makes up 1/3 of collagen and whose content indicates collagen synthesis.

10 y/o refugee boy with hx of transfusions 2/2 anemia. Exam shows conjunctival pallor and moderate splenomegaly. Results show low Hb and normal plts. Enzyme assay show low pyruvate kinase activity. What is function of pyruvate kinase? How does this condition lead to hemolysis? Why is spleen enlarged in this condition?

Converts PEP to pyruvate, generating one ATP. Decreased ATP means less transport of cations against conc gradient, leading to H2O and K+ loss, defective membrane architecture, and hemolysis. Reticuloendothelial cells in splenic red pulp are involved in removing damaged RBCs, and their increased activity in this condition leads to hyperplasia resulting in splenomegaly.

6 month old girl with growth retardation. Labs show hypoglycemia and ketoacidosis. Liver biopsy shows hepatic fibrosis without fat accumulation. Further analysis reveals abundant quantities of a multibranched polysaccharide with short outer chains. What is dx? What is deficient and what is normal function of deficient substance?

Cori disease Debranching enzyme is deficient. During glycogenolysis, glycogen phosphorylase shortens glycogen until 4 residues remain before branch point (the limit dextrin). At this point debranching enzyme has two functions: 1) glucosyltransferase cleaves outer 3 residues of the 4 glucose residues; 2) a-1,6-glucosidase removes the single remaining branch residue, producing free glucose and a linear glycogen chain that can be further shortened. In the absence of debranching enzyme, limit dextrins accumulate.

69 y/o female with Alzheimer's is found wandering outside after a day. She is dehydrated and mildly confused and has not consumed food or beverage for 24 hours. Her labs show normal blood glucose level despite prolonged fasting. What hormone(s) are responsible for glucose homeostasis during prolonged fasting? Where are the receptors for these hormones located? What is the action of cortisol once activated?

Cortisol and growth hormone Cortisol-within the cytoplasm; GH-membrane-bound Transported to the nucleus and control gene expression by binding to hormone-responsive DNA elements in the promotor region of target genes. Increases transcription of gluconeogenesis enzymes as well as those involved in lipolysis and proteolysis.

45 y/o male with hx of HIV non-compliant with meds has 2 weeks of chest pain and cough. On CXR there are nodules and hilar lymphadenopathy. What is dx and what are characteristics of organism? How do you test for the organism? What condition does this organism cause that is symptomatic? Where is the organism found in the environmen, how is it transmitted, and how does it spread in the body? How would you treat?

Cryptococcus neoformans, budding yeast with thick capsule. Not dimorphic. Culture on Sabouraud agar, highlight with India Ink stain (clear halo) and Mucicarmine (red inner capsule). Latex agglutination test detects polysaccharide capsular antigen and is more specific. Causes meningoencephalitis, which is sx. Can also cause lung nifection, but is usually asymptomatic. Found in soil and pigeon droppings, transmitted by respiratory route, not person-to-person. Hematogenous dissemination. Treat with amphotericin BB + flucytosine followed by fluconazole for cryptococcal meningitis.

65 y/o man in wool business. Has an ulcer with black eschar and significant edema. What is dx and causative organism? What toxins are involved? What is another toxin produced by a different organism that has a similar MOA to the toxin produced by causative pathogen?

Cutaneous anthrax caused by Bacillus anthracis Anthrax exotoxin: Consists of protective antigen, edema factor, and lethal factor. Edema factor in anthrax toxin acts as a calmodulin-dependent adenylate cyclase that increases cAMP concentration, causes accumulation of fluid within and between cells and results in suppression of neutrophil and macrophage function. Pertussis toxin (adenylate cyclase toxin) produced by Bordatella pertussis also works this way.

What processes occur in the cytosol? What processes occur in the mitochondria?

Cytosol: Glycolysis, FA synthesis, PPP Mitochondria: beta-oxidation of FAs, TCA cycle, and gluconeogenesis (carboxylation of pyruvate), urea cycle

34 y/o woman is screened for breast cancer using PCR to evaluate BRCA1 gene. What elements are required for PCR and what are the steps?

DNA template that includes target region to be amplified as well as flanking sequences adjacent to the target region. The oligonucleotide sequence of these flanking regions must be known in order to make the primers necessary to start PCR. DNA polymerase is used to replicate the DNA template from a pool of supplied doexynucleotide triphosphates using denaturing, annealing, elongation. Steps repeat to obtain millions of copies of the target DNA.

22 y/o female presents with fevers and arthralgias. She recently had unprotected sexual intercourse with a new male partner. She has several pustules on her arm and several joints are tender. What is the dx and organism? How does pathogen adhere to the mucosa? What other pathogens have this mechanism?

Disseminated gonorrheal infection caused by N gonorrhea Produces IgA protease which splits IgA at the hinge region, thereby facilitating mucosal adherence of bacteria. IgA protease also produced by N meningitidis, S pneumoniae, and H influenzae.

2 y/o boy with easy bruising and wounds s/p minor trauma. Skin is fragile and hyper-extensible, and an umbilical hernia is present. What does pt most likely have? What enzyme is possibly deficient and what does it do? What process in collagen synthesis is impaired because of this enzyme deficiency?

Ehlers-Danlos syndrome Deficiency in procollagen peptidase; cleaves terminal propeptides from procollagen in extracellular space. Crosslinking

30 y/o male presents with generalized sx, is an IVDU. He has a faint murmur on auscultation. Blood cultures grow enterococci strains. What is dx? What is the treatment and its MOA? What could cause resistance to this treatment?

Endocarditis Vancomycin; works by inhibiting cell wall peptidoglycan formation by binding D-ala D-ala portion of cell wall precursors. Resistance if there is amino acid modification from D-ala-D-ala to D-ala-D-lac

23 y/o male excretes large amount of fructose in his urine despite maintaining a moderate fructose intake. He has a hereditary defect in fructose metabolism, but is asymptomatic. What does the pt have? What enzyme compensates in order to metabolize fructose and what is frucose metabolized to? Describe the normal PW of fructose metabolism

Essential fructosuria; Fructokinase deficieny Hexokinase; Fructose converted to fructose-6-phosphate which then enters glycolysis Fructose converted to F1P by fructokinase; F1P converted to DHAP and glyceraldehyde by Aldolase B.

45 y/o male with recent dx of DM begins a medication that alters glucose within liver by increasing concentration of fructose 2,6-bisphosphate within hepatocytes. What conversion will be inhibited by this drug? What enzyme does this drug activate and what is the result? What enzyme does this drug inhibit and what is the result?

F6P to F1,6bisP will be inhibitied by fructose-2,6-bisphosphate F2,6BP activates phosphofructokinase-1, increasing glycolysis F2,6BP inhibits F1,6BP, decreasing gluconeogenesis

20 y/o male with weakness, malaise, dark urine. Was treated for bacterial skin infection several days ago. Exam shows scleral icterus, labs show anemia with elevated reticulocyte count. Abnormal erythrocytes seen on peripheral smear. What substance is this pt most likely deficient in? What is normal function of this substance? What predisposes the pt to hemolysis?

G6PD Rate limiting step of PPP. Catalyzes conversion of G6P to 6-phosphogluconolactone, which is then converted to 6-phosphogluconate. The PPP generates both NADPH and ribose-5-phosphate, which is used for nucleotide synthesis. Increased oxidative stress, i.e. infection

24 y/o male who presents with intermittent anemia, jaundice, and dark urine, especially after using certain drugs or after infection. Bite cells are seen on peripheral blood smear. What is dx? What other enzyme deficiency would result in a similar presentation? Describe the normal PW

G6PD deficiency Glutathione reductase deficiency leads to similar clinical scenario. G6PD is part of the PPP and generates the reducing agent NADPH, which detoxifies H2O2. Glutathione reductase catalyzes the reduction of oxidized glutathione.

43 y/o man gets stranded in desert. He has water but not enough food. The liver makes glucose from alanine, lactate, and glycerol. Part of this process involves forming PEP from oxaloacetate. What cofactor is required for this step? What reaction directly synthesizes this cofactor?

GTP (nucleoside triphosphate) Succinyl-CoA synthetase converts succinyl-coa to succinate in the TCA while also driving the synthesis of GTP.

18 y/o female in DKA, results in increased production of gluconeogenic precursors that are converted to glucose in the liver. What enzyme most likely provides the precursor substrates? What is the mechanism?

Glycerol kinase TGs stored in adipose tissue are metabolized to free FAs and glycerol by hormone sensitive lipase in response to low insulin and high catecholamine levels. Adipocytes are unable to metabolize glycerol, so it is secreted into the circulation and tranpsorted to the liver where it is phosphorylated to glycerol-3-phosphate by glycerol kinase. This produce is subsequently converted by G3P DH to DHAP which can be used to produce glucose through gluconeogenesis.

Increased nosocomial infections are due to what type of organism? What is the reason for the increased incidence of these infections?

Gram positive organisms. Most commonly S aureus and coagulase negative staphylococci. Increased incidence due to increased use of IV catheters, i.e. indwelling caths, central lines, etc.

3 month old has fever and lethargy. LP shows decr glucose and elevated protein. Gram negative coccobacilli are isolated and demonstrate little growth on blood agar, but grow well when incubated alongside S aureus. What is the causative pathogen? Why does it grow when supplemented with S aureus? What is this phenomenon known as?

H influenzae H infleunzae requires both X factor (hematin) and V factor (NAD+) to support growth. Sheep blood agar has insufficient nutrients for Haemophilus to grow. S aureus secretes V factor into the medium and facilitates release of additional X factor from beta hemolysis. Satellite phenomenon

34 y/o male has facial injury leading to ecchymosis. Several days later the bruise becomes green. What enzyme is responsible for the color change? What does this enzyme breakdown and what are the products? What product is responsible for green color?

Heme oxygenase Breaks down heme into biliverdin, CO, and ferrous iron. Biliverdin

5 y/o male with somnolence, lethargy, oliguria. Developed diarrhea several days ago that later become frankly bloody. Labs show elevated BUN and creatinine, and fragmented erythrocytes. What is dx? What most likely caused current condition?

Hemolytic uremic syndrome EHEC (0157:H7) from consumption of undercooked, contaminated ground beef.

5 y/o pt has difficulty seeing. He is tall, thin, and has elongated limbs. Exam shows bilat lens subluxation. He dies 4 years later from a CVA. Autopsy shows MCA thrombosis and old renal infarcts. What is dx? What is age of presentation. What are characteristics of condition? What is the most common deficient enzyme and its required cofactor? How is it treated?

Homocystinuria (AR) Pts present b/w 3-10 y/o Pts first present with ectopia lentis. Half of pts have intellectual disability. Other manifestations are include marfanoid habitus. Cystathionine beta-synthase is deficient, requirs pyridoxine (B6) 50% pts respond to high doses of pyridoxine. Additional tx includes dietary restriction of methionine. Also increase cysteine, B12, and folate in diet.

72 y/o female found laying on floor after two days, has not had food or water. Serum glucose is 72 mg/dL and urine is positive for ketones. What enzyme is responsible for serum and urine findings? Where is this enzyme found and what does it do? How is this enzyme activated?

Hormone sensitive lipase Found in adipose tissue, catalyzes the mobilization of stored TGs into free FAs and glycerol (lipolysis). In response to stress hormones, which stimulate Gs protein-coupled receptords > incr cAMP production and activation of PKA, which phosphorylates and activates HSL.

35 y/o female presents with itchy rash onset this am. Pt returned from resort in Mexico. Exam shows diffuse, pruritic, papulopustular rash on trunk and extremities. What is dx and causitive organism? What type of organism is this and characteristics of organism?

Hot tub folliculitis caused by pseudomonas aeruginosa Gram negative motile rod that is oxidase positive, and produces green pigment. Nonlactose fermenting.

There is an outbreak of Influenza A in a small town, of a strain similar to the one that circulated the year prior. The majority of the population remains uninfected. What immune response is responsible for this? What antibodies are the most important source of protection in this case?

Humoral immune response Antibodies directed against hemagglutinin are the most important source of protection.

8 y/o boy has vomiting and lethargy after going 24 hours without food. Labs show low glucose and elevated AST and ALT. What is the dx? What pathway is defective, and what deficiency is the most common cause? Deficiency of what other substance can lead to similar sx?

Hypoketotic hypoglycemia Fatty acid beta-oxidation is defective, most commonly caused by acyl-CoA DH deficiency Carnitine deficiency prevents FAs from being transported into mitochondria for beta-oxidation and causes similar features.

A man has tuberous meningitis that is caused by M tuberculosis with decreased activity of intracellular catalase peroxidase. What drug will this strain be resistant to and why? What is another way this strain can become resistant to this drug?

Isoniazid, which uses mycobacterial catalase peroxidase to become activated and subsequently inhibit mycolic acid synthesis. Resistance can also develop through genetic modification of the INH binding site on the mycolic acid synthesis enzyme.

2 y/o boy presents with diarrhea, fatigue, and abd cramps. Stool is foul-smelling and frothy. Pt is treated with metronidazole but sx persist. What is likely dx? What is deficient? What is normal PW? What are causes of this condition?

Lactose intolerance Lactase deficiency Lactose is hydrolyzed by lactase on brush border into glucose and galactose. Primary: Due to genetically regulated reduction of lactase production. Secondary: Acquired, due to inflammation or infection (i.e. giardiasis). Causes by damage and sloughing of cells that are replaced by immature cells with low lactase concentrations.

65 y/o female undergoing chemo is hospitalized with fever, HA, ataxia, confusion. Two days later, a 26 y/o has fever, NVD, myalgia, and spontaneously delivers premie with generalized rash. Others in the area have similar sx and all consumed food products from single processing facility. What is the causative organism and its characteristics? How is it transmitted? What is the treatment?

Listeria monocytogenes, gram positive intracellular rod. Forms rocket tails via actin polymerization that allow intracellular movement and cell-to-cell spread across cell membranes, thereby avoiding antibody. Characteristic tumbling motility. Transmitted by consuming unpasteurized dairy, cold deli meats, transplacentally, or vaginally during birth. Treat with ampicillin

62 y/o male presents to the ED c/o sudden-onset fever, shaking chills, SOB, and productive cough. He has 40 pack year smoking hx. CXR reveals consolidation in L upper lobe, and gram stain of sputum shows numerous polymorphonuclear leukocytes and gram-positive cocci in pairs. What is the dx and causative organism? What are characteristics of this organism? What is the major virulence factor of this bacteria?

Lobar pneumonia caused by Streptococcus pneumoniae. Gram positive, diplococci that exhibits partial (alpha) hemolysis on blood agar and is bile soluble and optochin sensitive. Major virulence factor is a thick polysaccharide capsule that encases the organism and prevents phagocytosis and complement binding.

A 34 y/o female presents with abd pain and melena, fatigue and weight loss over 2 months. FHx includes colon, endometrial, and ovarian cancer. Colonoscopy shows mass in ascending colon that is confirmed to be adenocarcinoma. What is pt's most likely dx? What repair mechanism is deficient in this pt? How does this deficient mechanism usually work and in what phase of the cell cycle?

Lynch syndrome (HNPCC) Mismatch repair New strand is recognized by MutS homolog, MutL homolog is recruited, and complex slides along DNA molecule until daughter strand 'nick' is encountered. Exonuclease 1 is loaded and activated by repair complex. Mismatched nucleotides are removed, gap is filled and resealed. Usually in G2 phase.

4 -day-old infant with abnormal movements, tonic posturing, poor feeding, vomiting, and irritability. Diapers smell like caramelized sugar. What is dx? What is pathophys? What is treatment?

Maple Syrup Urine Disease (AR) Branched-chain amino acids (Isoleucine, leucine, valine) are usually degraded by being transaminated to their respective a-ketoacids, then metabolized by branched-chain a-ketoacid DH complex. Mutations in this complex lead to accumulation of the a-ketoacids, leading to neurotoxicity. Treatment is dietary restriction of isoleucine, leucine, and valine as well as giving thiamine supplementation.

15 y/o presents with poor muscle endurance, and occassional muscle cramping and urine discoloration after strenuous activity. Exercise intolerance improves after drinking oral glucose solution. What is the dx? What enzyme is deficient? What metabolic process is defective in this condition?

McArdle dz (type V glycogen storage dz) Myophosphorylase (glycogen phosphorylase in muscle tissue) Muscle glycogenolysis

10 week boy receives first dose H influenzae type b conjugate vaccine 2 weeks ago but had an allergic reacction. It was decided that he would not be given additional doses. What infection is this pt at risk of getting? Why?

Meningitis Without protection from the vaccine, the child is at risk for invasive disease caused by Hib, such as meningitis, bacteremia, pna, and epiglottitis.

23 y/o female has 10 days of nonproductive cough, low-grade fever, HA, malaise. She has rales, and CXR shows patchy consolidation. Labs show mild anemia and elevated lactate DH level. Pt is treated for mycoplasma pneumonia with azithromycin and she recovers. What is pathogenesis of this disease and cause of anemia? What are other manifestations of this condition?

Mycoplasma pneumoniae binds to oligosaccharide (I-antigen) that is present on epithelium and on surface of RBCs. This leads to the formation of cross-reacting IgM antibodies (cold agglutinins) that attach to RBCs, activate complement system, and cause erythrocyte lysis. Other manifestations include Stevens-Johnson syndrome, joint pain, encephalitis, cardiac rhythm disturbances, and bullous myringitis.

8 y/o boy with exercise intolerance. Pt experiences fatigue, muscle pain, and cramps during exercise and muscle stiffness s/p strenuous activity. No lactate is detected after exercise, and muscle biopsy shows absent lactate DH activity. Which substance's depletion leads to inhibition of glycolysis? Why is this substance depleted? What conversion is this substance a cofactor of?

NAD+ In anaerobic glycolysis, NAD+ is regenerated from NADH when pyruvate is converted to lactate via lactate DH. If lactate DH is deficient, NAD+ cannot be regenerated. Conversion of glyceraldehyde-3-P to 1-3-bisphosphoglycerate in glycolysis.

What cytoplasmic protein interacts with mRNA after it leaves the nucleus and what does it do? What are the important steps that happen before mRNA leaves the nucleus?

P bodies, involved in mRNA regulation and turnover and also function as mRNA storage. Contains exonucleases, decapping enzymes, and microRNAs. 5'-capping, poly A tail addition, and intron splicing all occur in the nucleus before mRNA is released into cytoplasm.

52 y/o male has abd pain and watery diarrhea, worsening over the last month. He has a hx of EtOH abuse and has a pigmented scaly skin rash that worsens with sun exposure. What is dx? What deficiency is causing these symptoms? What is this deficient substance a precursor to and what enzymes does it affect? List specific important enzymes affected by the deficiency

Pellagra Niacin (B3) deficiency Niacin is precursor for NAD and NADP, which are important cofactors for many dehydrogenase and reductase enzymes. Isocitrate DH, a-KG DH, malate DH in the TCA cycle.

52 y/o female presents with photosensitive rash, is irritable, hostile, and disoriented. She restricts her diet for weight control. Exam shows scaly rash. What is dx and what is deficient in pt? What are the classic manifestation in this condition? What is the deficient substance an essential component of? How is the deficient substance obtained?

Pellagra due to niacin (B3) deficiency 3 Ds: Dermatitis, diarrhea, dementia Niacin is essential component of NAD and NADP which participate in redox metabolism, specifically DH enzymes. Niacin is obtained through dietary intake or synthesized endogenously from tryptophan.

43 y/o male presents with 4 week hx of cough. Previously had cold-like sx that resolved after 10 days, but cough persists. Some cough attacks are so severe that they cause pt to vomit. Pt UTD on all vaccines, but has not been to the doctor in many years. What is dx and causative organism? What type of organism is this? Who is at risk for getting infected?

Pertussis, caused by Bordetella pertussis Gram negative, aerobic coccobacillus. Adults who have not received boosters are at risk. Children are vaccinated so it is not common in that population anymore.

4-month old boy who was adopted is tremulous, has upward eye deviation, and BUE and BLE shaking. BP is 90/40, hr 120, RR 30. The child is fair-skinned with blue eyes and has a musty odor. What is the dx? What is the deficient enzyme? What AA becomes essential? People of what ethnic background are most likely to suffer from the classical variant of this condition? Explain the fair complexion of the pt What is the therapy?

Phenylketonuria Phenylalanine hydroxylase Tyrosine Scandinavian Excess phenylalanine inhibits tyrosinase, which normally results in downstream production of melanin. Dietary restriction of phenylalanine

34 y/o male with a hx of HIV presents with 3 days of fever, chills, productive cough, and left-sided CP with deep breathing. Pt is compliant with meds and CD4 count was 480 one month ago. Labs show elevated leukocytes with left shift. What is dx and most likely organism?

Pneumonia 2/2 Streptococcus pneumonia. S pneumonia is most common cause of community-acquired pna in both HIV and non-HIV pts.

3 y/o girl with several months of fatigue and difficulty walking. Ambulates normally but quickly becomes week and tired. Hx of mild motor delays but developmentally normal otherwise. Exam shows mildly decreased power in all extremities. No ataxia. 1/6 systolic murmur and S3 gallop. Glucose is low and creatine kinase is high. Biopsy shows low carnitine content. What is the dx? What metabolic process is defective? What substance has a deficient synthesis and what does this lead to?

Primary carnitine deficiency Fatty acid degradation (beta oxidation) Acetyl CoA; Without acetyl coa, cardiac and skeletal myocytes cannot generate ATP from FAs and the liver cannot synthesize ketone bodies (ie acetoacetate) when glucose levels are low.

67 y/o male with severe fatigue and weight loss over the past several months. Evaluation reveals a mutation leading to persistent activation of signal transducers and activators of transcription (STAT) proteins. What is the most likely dx? What is mutated? What is pathogenesis?

Primary myelofibrosis Mutation in the nonreceptor cytoplasmic tyrosine kinase, Janus kinase 2 (JAK2) Atypical megakaryocytic hyperplasia stimulates fibroblast proliferation, resulting in progressive replacement of the marrow space by extensive collagen deposition.

Elderly female being treated for E. coli develops diarrhea and a fever. What is dx? What is MOA of pathogen? What are the special contact requirements for healthcare personnel?

Pseudomembranous colitis 2/2 C. diff C. diff produces Toxin A (enterotoxin that binds to brush border of gut and alters fluid secretion) and Toxin B (cyto toxin that disrupts cytoskeleton via actin depolymerization). Persons should wash hands with soap and water, wear nonsterile gloves and a gown when taking care of pts with C. diff.

A pregnant female develops fever and macular-papular rash that spreads from face to chest and trunk. Exam shows postauricular lymphadenopathy. What is dx? What complications is mother at risk for? What complications is infant at risk for?

Rubella Mother can get rash, lymphadenopathy, polyarthritis, polyarthralgia Infant can get triad of cataracts, deafness, and cardiac abnormality (PDA)

78 y/o female has bleeding of gums. She is on a tea and toast diet. What is dx? What does the deficient substance usually do? Where does this process occur?

Scurvy (Vit C deficiency) Hydroxylation of proline and lysine residues RER

54 y/o male presents with worsening fever, cough, and SOB after being treated for Influenza A one week ago. What is dx and most likely causitive organisms? What is mechanism of current condition?

Secondary bacterial infection; S. pneumoniae, S. aureus, H. influenzae. Influenza leads to loss of cilia and increased free sugar in the respiratory tract, creating a favorable environment for the above bacteria to grow.

32 y/o male presents with 2 weeks of fever, malaise, arthralgia. He has fever, tachy, and enlarged lymphadenopathy. He has diffuse maculopapular rash. Serum aminotransferase is elevated. What is the dx? What are the tests to dx and mechanisms? Characteristics of this specific condition?

Secondary syphilis VDRL: Combines serum with cardiolipin-cholesterol-lecithin antigen. Aggregation or clumping is positive. Nonspecific. Treponemal tests evaluate for ABs targeted against T pallidum. Constitutional sx, mac-pap rash, condylomata lata, lymphadenopathy, patchy hair loss.

3 y/o male immigrant has fever, malaise, and painful, swollen right knee. He is hypotensive and tachycardic. He recently recovered from acute otitis media. What is dx? What is responsible organism and characteristics? What virulence factor allows this organism to spread? What does this pathogen require for growth?

Septic arthritis H influenzae, gram negative, pleomorphic coccobacillus Polysaccharide capsule Requires X factor (hematin) and V factor (NAD+) to grow

24 y/o sexually active female reports joint pain. On exam she has vesicuopustular lesions are present on the upper extremities. The right knee is warm, swollen, and tender with DROM. What is the dx and causitive organism? What type of organism is this? What is treatment?

Septic arthritis caused by N gonorrhea. Gram negative diplococci Treat with ceftriaxone + (azithromycin or doxycycline)

A 7 y/o African-American male has a hx of hospitalizations for severe pains in back and extremities. He gets tired at the end of the day. He conjunctival pallor on examination, and low Hb. What is his dx? What is mutation associated with this condition? What promotes the painful episodes this pt has, and how do they occur?

Sickle cell anemia Valine substitutes glutamate at position 6 of the beta globin chain Sickling is pormoted by conditions associated with low oxygen levels, increased acidity, or low blood volumes. Sickled cells are not flexible enough to pass through microvasculature so they impede blood flow and cause microinfarcts in tissues, causing painful vasoocclussive crises.

What is the most common site of S aureus?

The anterior nares are the most common site of colonization for both methicillin-sensitive and methicillin-resistant staph aureus.

34 y/o Eastern European immigrant presents with 3-month hx of productive cough, night sweats and low-grade fever. Sputum cultures grow budding yeast that form germ tubes at 37 C. What is his underlying dx? What is the most likely organism grown in the culture? What structure is specific to this organism? Where where was this organism before entering the sputum?

The pt likely has TB based on hx The culture grew Candida albicans Germ tubes are specific to Candida albicans Candida contributes to the normal flora of skin, mouth, vagina, and intestine. It was likely in the pt's oral cavity before contaminating the sputum culture.

44 y/o alcoholic homeless man presents agitated and confused. En route he was given IV fluids with dextrose. He has bruises on forehead, arms, and shins. He has bilat horizontal nystagmus, decr lateral eye movements. Also has unsteady gait with widely-spaced legs and short steps. HIs EOM were intact prior to arrival. What is deficient in this pt? What enzymes require the deficient substance in this pt? What is the result of administering glucose to this pt?

Thiamine alpha-ketoglutarate DH, transketolase, pyruvate DH Wenicke encephalopathy: Acute confusion, opthalmoplegia, ataxia due to decreased thiamine demand.

29 y/o female w/ PMH of HIV noncompliant with meds presents with fatigue, weakness, and anorexia x2 weeks. MRI head shows 2 ring-enhancing focal lesions with surrounding edema in the right frontal lobe. What is dx and organism? How is this organism transmitted? What is treatment? If the pt does not respond to treatment after several weeks, what is the next most likely diagnosis? What is this usually caused by? The lesions would show an abnormal population of what types of cells in this latter case?

Toxoplasmosis, caused by Tocoplasma gondii. Cysts in meat, oocysts in cat feces, can cross placenta. Treat with Sulfadiazine + pyrimethamine Primary central nervous system lymphoma EBV is identified in most cases of PCNSL B-lymphocytes

14 y/o boy has excessive urination and thirst, has lost 10 lb over the last 3 weeks. He has markedly elevated blood glucose and high A1c. What is dx? What is treatment? Describe the target of this treatment Explain MOA of treatment What does this treatment increase the synthesis of?

Type 1 DM Insulin Surface receptor for insulin is a transmembrane protein with intrinsic tyrosine kinase activity in its cytoplasmic domain. Insulin binding activates tyrosine kinase, leading to phosphorylation of insulin receptor substrate 1 (IRS-1), which then acivates several intracellular pathways. Insulin increases the synthesis of glycogen(via protein phosphates which dephsophorylates glycogen synthase), proteins, FAs, and nucleic acids.

42 y/o woman with Parkinson's disease. Genetic analysis shows loss-of-function mutation leading to an accumulation of misfolded proteins. What process is defective in this pt? Describe the process

Ubiquination Ubiquitin is a protein that attaches to other proteins to label them for degradation. The modified proteins enter the proteasome and are degraded into small peptides. Impairment of ubiquitin-proteasome system can lead to neurodegenerative disorders.

Infant born to a IVDU mother presents with oral thrush, interstitial pneumonia, and lymphopenia during first year of life. What is dx? What could have prevented this condition?

Vertical transmission of HIV Prenatal antiretroviral therapy (2 NRTIs + 1 protease inhibitor/integrase inhibitor/NNRTI)

78 y/ o male presents with one month of dyspnea, weakness, fatigue, palpitations, and paresthesias in BLE. Daughter states pt has not been taking care of himself. Exam shows sensory deficits and indications of heart failure. What is the dx? What is the cause of the condition and what else can it cause? What are the other variations of the condition?

Wet beriberi (peripheral neuropathy, cardiac involvement) Thiamine deficiency, can also cause Wernicke-Korsakoff syndrome (confusion, oculomotor abnormalities, permanent memory deficits) Other variation is dry beriberi, which does not include cardiac involvement.

Researcher develops mRNA sequences composed of CUC and CUU trinucleotide repeats. Both produce polypeptide chains containing leucine. What principle explains this observation?

Wobble Hypothesis: The first two nucleotide positions on mRNA require traditional base-pairing with their complementary nucleotides on tRNA, but the last position may undergo less stringent base pairing.

40 y/o female with 3 months limitation of physical activity due to fatigue. She had a positive PPD 7 months ago with nl CXR, and has been compliant with prescribed meds. Exam shows pallor. Lab show low Hb and low hematocrit, MCV is 72. Bone marrow aspirate shows sideroblastic anemia. Decreased activity of which enzyme explains anemia? What caused the anemia and how?

delta-aminolevuinate synthase Isoniazid caused anemia. It blocks pyridoxine phosphokinase, leading to pyridoxine deficiency. Pyridoxines active form is the cofactor for delta-amiolevulinate synthase, which catalyzes the rate-limiting step of heme synthesis.

RNA molecule that has 75-90 nucleotides? What is at the 3' end of the molecule?

tRNA CCA tail, which is the acceptor site