Week 1 Block 13: BMR

Question 1

(1) Dx: acute onset abdominal pain, nausea, & confusion. Several minor episodes of ab pain correlate with drinking alcohol. Serum lipase, liver function tests, and CT scan of ab show no abnormalities. urine normal & dark upon standing. IV dextrose improves sx. (2) Pathogenesis (3) Explanation for why IV dextrose helps

Answer 1

(1) Acute intermittent porphyria (AIP) (2) Deficiency of Porphobilinogen deaminase (aka hydroxymethylbilane synthase, which converts Porphobilinogen to hydroxymethylbilane). Build up of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) toxic to human tissues(3) Glucose loading decreases porphyrin synthesis by repressing ALA synthase activity, thus alleviating abdominal pain and neuropsychiatric manifesations of AIP

Question 2

(1) Principal source of blood glucose after 12 to 18 hours of fasting (2) Major enzymes & steps involved in this process

Answer 2

(1) Gluconeogenesis (2) I. Pyruvate carboxylase (biotin-dependent carboxylation) converts pyruvate to oxaloacetate II. Phosphoenolpyruvate carboxykinase (PEPCK) converts oxaloacetate to PEP III. Fructose 1,6-bisphosphatase (bypassing phosphofructokinase) IV. Glucose-6-phosphatase (bypassing hexokinase)

Question 3

(1) Dx: newborn w/ vomiting, irritability, lethargy several days after birth, “burned sugar” diapers (2) Defect (3) Normal reaction involves

Answer 3

(1) Maple syrup urine disease (2) Branched-chain alpha-ketoacid dehydrogenase (3) Requires several coenzymes: Thiamine pyrophosphate, Lipoate, Coenzyme A, FAD, NAD (mnemonic: “Tender Loving Care For Nancy/Newborns”)

Question 4

(1) Defect suggested by hypoglycemia after prolonged fasting with inappropriately low levels of ketone bodies (2) Enzyme that catalyzes first step in relevant mechanism (3) Most commonly deficient enzyme

Answer 4

(1) Impaired Beta-oxidation (2) Acyl-CoA dehydrogenase catalyzes first step in Beta-oxidation pathway and is (3) most commonly deficient enzyme

Question 5

(1) Mechanism behind TNA-alpha decreased insulin-mediated glucose uptake (2) Similar substances having same effect and mechanism

Answer 5

(1) Aberrant serine and threonine residue phosphorylation by serine kinase leads to insulin resistance (2) These aberrant phosphorylations can occur in presence of TNF-alpha, catecholamines, glucocorticoids, and glucagon

Question 6

(1) P50 in context of hemoglobin (2) High oxygen affinity Hb p50 & curve shift (3) Physiological/compensatory consequences of high oxygen affinity Hb & why

Answer 6

(1) P50 = partial pressure of oxygen at which hemoglobin is 50% saturated (2) High-oxygen-affinity Hb’s have decreased P50 that is represented by leftward shift of oxygen-dissociation curve (3) Reduced ability to release oxygen within peripheral tissues, leading to renal hypoxia, increased erythropoietin synthesis, and compensatory erythrocytosis

Question 7

Collagen synthesis steps, emphasizing intracellular (inside fibroblasts) vs. extracellular (outsibe fibroblasts) steps

Answer 7

Procollagen synthesized within ER as a central helical structure flanked by globular extensions. It is then transported through Golgi apparatus and released into extracellular space, where it is converted into tropocollagen by procollagen peptidases that remove the globular portions of the molecule. The resulting tropocollagen monomers self-assemble into collagen fibrils that are then covalently crosslinked by lysyl oxidase.

Question 8

(1) Most likely dx/affected body part if PRPP synthetase gene mutation that results in increased V max for enzyme (2) Mechanism

Answer 8

(1) Gout/Joints (2) Increased PRPP synthetase leads to increased production of purines, which results in hyperuricemia

Question 9

(1) Dx: ankle pain & swelling, synovial fluid w/ negatively birefringent crystals under polarized light microscopy (2) Acute Tx & its mechanism

Answer 9

(1) Monosodium urate crystals - Gouty arthritis (2) Colchicine useful in acute management of gouty arthritis because it inhibits chemotaxis of neutrophils by preventing microtubule formation

Question 10

(1) Dx: ataxia, episodic erythematous and pruritic skin lesions, loose stools, loss of neutral aromatic amino acids in urine (2) Major associated condition & its symptoms (3) Explanation for association

Answer 10

(1) Hartnup disease: Excess loss of dietary tryptophan, resulting from defective intestinal and renal tubular absorption of that (neutral) amino acid (2) Niacin deficiency (Pellagra): Diarrhea, Dementia (also hallucinations), Dermatitis (e.g., Casal necklace or hyperpigementation of sun-exposed limbs) (3) Niacin (nicontinamide/vitamin B3) synthesized from tryptophan & tryptophan is essential amino acid

Question 11

Molecular pathophysiology of HbS that makes it more severe condition than HbC disease

Answer 11

HbS contains valine in place of glutamic acid in 6th amino acid position of the beta subunit. This promotes hydrophobic interaction among hemoglobin molecules and results in polymerization of HbS molecules and red blood cell distortion

Question 12

(1) Enzyme defect if 34 yo female develops moderate hyperglycemia in her first pregnancy and dx w/ gestational diabetes, improves after delivery, genetic (2) Role of this enzyme (3) Explaining it in this patient’s context

Answer 12

(1) Glucokinase is a (2) glucose sensor within pancreatic beta cells. (3) Inactivating mutations of the enzyme result in mild hyperglycemia that can be exacerbated by pregnancy.

Question 13

(1) Dx: urine samples from apparently healthy 23 yo male repeatedly positive for reducing sugar but negative for glucose, PMH insignificant, not follow any specific diet (2) Explain

Answer 13

(1) Essential fructosuria - defect/deficiency in enzyme Fructokinase (2) Unlike hereditary fructose intolerance (aldolase B) and classic galactosemia (galactose-1-phosphate uridyltransferase), essential fructosuria is a benign disorder

Question 14

(1) Inhibition of lactate dehydrogenase in strenuously exercising skeletal muscles would eventually lead to an inhibition of glycolysis due to intracellular depletion of what? (2) Explain

Answer 14

(1) NAD+ (2) Under anaerobic conditions, NADH transfers protons to pyruvate to form lactate and to regenerate NAD+. NAD+ is required to convert glyceraldehyde-3-phosphate to 1-3-bisphophoglycerate in glycolysis

Question 15

Key functions of important apolipoproteins: (1) ApoA-1 (2) ApoB-48 (3) ApoB-100 (4) ApoC-II (5) ApoE-3 & -4

Answer 15

(1) ApoA-I: LCAT activation (cholesterol esterification) (2) ApoB-48: Chylomicron assembly and secretion by intestine (3) ApoB-100: LDL particle uptake by extrahepatic cells (4) ApoC-II: Lipoprotein lipase activation (5) ApoE-3 & -4: VLDL and chylomicron remnant uptake by liver cells

Question 16

Prokaryotic 16S rRNA in ribosomes: (1) Found where (2) Contains what (3) Plays what role

Answer 16

(1) Found in 30S ribosomal subunit (2) Contains sequence complementary to Shine-Dalgarno sequence on mRNA (3) Binding of these two complementary sequences is necessary for initiation of protein translation

Question 17

(1) To what are individual subunits of hemoglobin structurally analogus? (2) Monomeric Hb subunits on oxygen-dissociation curve

Answer 17

(1) Myoglobin (2) Hyperbolic oxygen-dissociation curve similar to that of myoglobin

Question 18

Toxicities of Vitamin A overdose

Answer 18

Vitamin A overdose can result in intracranial hypertension, skin changes, and hepatosplenomegaly

Question 19

P bodies role & where

Answer 19

Cytoplasmic P bodies play an important role in mRNA translation regulation and mRNA degradation

Question 20

Purpose of Homeobox genes

Answer 20

Code for DNA-binding transcription factors that play an important role in morphogenesis (i.e., proper formation and placement of tissues, organs, and structural elements of the body)

Question 21

Leptin: (1) what is it (2) where/how is it produced (3) how does it act (4) what results from leptin mutations

Answer 21

(1) protein hormone (2) produced by arcuate nucleus of hypothalamus to (3) inhibit production of neuropeptide Y (decreasing appetite) and stimulate production of alpha-MSH (increasing satiety) (4) Mutations in leptin gene or receptor result in hyperphagia and profound obesity

Question 22

(1) Mechanism for which Protein Kinase A is responsible (2) E.g., of receptors that use this mechanism

Answer 22

(1) intracellular effects of G-protein / adenylate cyclase second messenger system (2) Some hormone receptors that use this mechanism include TSH, glucagon, PTH, and beta-adrenergic receptors

Question 23

Cellular site of rRNA synthesis

Answer 23

Nucleolus (dark intranuclear body visible both by light microscopy and electron microscopy)

Question 24

(1) General definition/explanation of transamination (2) Cofactor in transamination reactions (3) In what other kinds of reactions does this cofactor participate

Answer 24

(1) Transamination reactions typically occur between an amino acid and an alpha-keto acid. Amino group from amino acid transferred to alpha-keto acid, and the alpha-keto acid in turn becomes an amino acid (2) Pyridoxal phosphate (vitamin B6) serves as a cofactor in amino acid transamination and in (3) decarboxylation reactions

Question 25

(1) What is PI3K/Akt/mTOR pathway, and its important functions (2) Result of mutations in its growth factors

Answer 25

(1) Intracellular signaling pathway important for anti-apoptosis, cellular proliferation, and angiogenesis (2) Mutations in growth factor receptors, Akt, mTOR, or PTEN that enhance the activity of this pathway contribute to cancer pathogenesis

Question 26

(1) Dx: painful lesions on lips & corners of mouth, mildly demented and lives alone, riboflavin excretion low (2) Explain what enzyme/process may be low

Answer 26

(1) Riboflavin deficiency (2) Succinate dehydrogenase - Riboflavin (vitamin B2) is precursor of coenzymes FMN and FAD. FAD participates in tricarboxylic acid cycle as a coenzyme of succinate dehydrogenase, which converts succinate into fumarate.

Question 27

Base excision repair: (1) Purpose (2) Order of enzymatic activity in process

Answer 27

(1) Used to correct defects in single bases induced spontaneously by exogenous chemicals (2) In this process, glycosylases remove defective base, and the corresponding sugar-phosphate is cleaved and removed by endonuclease (cleaves 5’ end), followed by action of lyase (cleaves 3’ sugar-phosphate). DNA polymerase then replaces missing nucleotides and ligase reconnects the DNA strand.

Question 28

(1) Mechanism(s) by which secondary lactase deficiency occurs (2) Sx (3) Another name for lactose

Answer 28

(1) Can occur after viral gastroenteritis or other diseases that damage intestinal epithelium (2) Abdominal distention, flatulence, and diarrhea after lactose ingestion (3) Lactose (galactosyl Beta-1, 4-glucose)