2015-05-04 Biochem UWorld

jdlevenson's version from 2015-05-09 14:09


Question Answer
Glucose inducesDecreased AC activity, decreased cAMP
Lac operon consists ofRegulatory, promoter, operator and 3 structural genes.
Lac operon regulation, lack of glucose leads to whereas lactose leads toLack of glucose -> increased adenylyl cyclase, increased cAMP and increase catabolite activator protein/ CAP; lactose availability -> blocks repressor protein and so removed from operator region. So, only with (1) low glucose -> CAP and then (2) lactose availability -> repressor removed will Lac genes be expressed


Question Answer
RBC metabolismGlycolysis (energy for survival) and HMP Shunt (NADPH to prevent oxidant damage)
HMP Shunt goalTo provide 2 NADPH from abundant glucose-6-P and return it as fracture-6-P. It has oxidative (irreversible, NADPH producing) and non-oxidative (reversible) portions).
HMP Shunt produces NADPH for and ribose for? NADPH -> Glutathione reduction (GSSG -> GSH), Fatty Acid Synthesis and Cholesterol synthesis. Ribose -> nucleotide synthesis.
HMP shunt occurs inCytoplasm.
Deficiency in HMP shunt (G6PD enzyme) vs. deficiency in glycolysis (95% time it is from pyruvate kinase deficiency, in terms of hemolysis?HMP deficiency -> episodic hemolysis due to oxidant stress and Glycolysis deficiency -> chronic hemolysis.


Hb at <7 weeks : Zeta and epsilon, from yolk sac; Hemoglobin Gower (-> Hemoglobin Portalnd -> Hemoglobin Gower 2)
Question Answer
Hb 7 months to gestation -> first 6 months of lifeHbF, two alpha and two gamma
HbA2 alpha and 2 beta; beta replaces in first 12 months
Hemoglobin BartFour gamma protein subunits/ no alpha. Found in homozygous alpha-thalassemia. No alpha chains. Very high affinity for oxygen -> does not release -> tissue hypoxia. Homozygous alpha thalassemia -> Hydrops fetalis and death in utero .
Hemoglobin GowerEarliest hemoglobin found in fetus. Synthesized by yolk sac.
Hemoglobin TautDeoxygenated form. Low affinity for 02. TAUT -> TISSUES.
Hemoglobin RelaxedHigh affinity for 02. Positive cooperativity and negative allostery.
Fetal Hb has () affinity for and () affinity forFetal Hb has lower affinity for 2,3 BPG and higher affinity for 02.
HbC mutationLysine instead of Glutamic Acid
HbS, anoxic conditions leads toAggregation of Hb molecules/ polymerization -> meshwork of fibrous polymers.
What promotes sicklingLow oxygen, Increased Acidity and Low Blood Volume
HbS will allowHydrophobic interaction among Hb molecules
Globin chains normally areCompactly folded due to nonpolar hydrophobic residues in interior and charged polar residues on surface.
The binding and affinity for oxygen and 2, 3 DPG by HbS and C vs HbASAME.
Hemoglobin MMutation in heme binding pocket in A or B chain leading to formation of iron phenolate complex that resists the reduction of iron to ferrous state/ maintains it in ferric state.
HbS affects A or BB subunit.


Question Answer
Biotin, pyruvate carboxylase isPyruvate -> Oxaloacetate. Part of gluconeogenesis or replenish TCA cycle.
Biotin, acetyl-coA carboxylaseAcetyl coA -> Malonyl coA for fatty acid synthesis.
Biotin, propionyl carboxylasePropionyl coA -> Methylmalonyl coA as part of way of taking odd chain fatty acids, branched chain amino acids, MET and THR to make Succinyl coA for Krebs


Question Answer
Microarrayhybridization of large number of probes at once
Southwestern blottingAnalyzes DNA-binding proteins; they are recognized by their ability to bind specific oligonucleotide probes.


Question Answer
Aberrant serine and threonine residue phosphorylation by serine kinaseleads to insulin resistance.
What can phosphorylate serine and threonine to cause insulin resistanceTNF-alpha, catecholamines, glucocorticoids, glucagon.
Serine kinases phosphorylate what part of insulin receptorBeta subunit’s serine residues. Phos of threonine has similar affects.


Question Answer
In Gq pathway, what is role of DAGActivates protein kinase C.
PPAR gamma leads toImproved insulin sensitivity.
Thiazolidinediones/ TZD work howPPAR gamma activation -> decrease blood sugar.
Collagen is made most of what amino acidGlycine.
Vitamin C is involved in what part of collagen synthesisHydroxylation of proline -> Hydroxyproline. Lysine also must be hydroxylated.
Hydrogen and disulfide bonds make up triple helix for collagen. When there are problemsOsteogenesis Imperfecta.
Triple helix formation happens in nucleus and is formed fromInterchain, not intrachain, disulfide bonds form at the C-terminus between 3 pro-alpha chains aligning the helical domains into a conformation favorable for triple helix.
Collagen formation step that occurs outside of nucleusN and C terminal regions are cleaved from triple helix by procollagen peptidases forming water soluble triple helical collagen subunits/ tropocollagen. Tropocollagen self-assembles into collagen fibrils which are then crosslinked by lysyl oxidase.
Ehlers Danlso symptomsHypermobile joints, fragile hyperelastic skin and easy bruising from decreased tissue strength and support. More soluble collagen that does not properly cross link.
Ehlers Danlos caused byMutations affecting genes or enzymes such as lysyl hydroxylase or procollagen peptidase, both occurring outside cell*. Leads to MORE SOLUBLE collagen.


Question Answer
Nitrites poison howOxidize heme iron to ferric state. Ferric, 3+, cannot bind oxygen and becomes methemoglobin.
Methemoglobin causes shiftLeft. Increased affinity.
ALL predominantly affectsChildren. Nonspecific symptoms.
CLL findingsLymphocytosis, smudge cells, increased expression of BCL-2, similar to follicular lymphomas.
Chronic myeloproliferative disorders (PVera, ET, PMF) have what mutationCytoplasmic tyrosine kinase JAK2 ->> cytokine independent activation of STAT txn factors. Mutation ins Phe instead of Val leading to constitutive activation.
Which chronic myeloproliferative disorder does not have mutation in cytoplasmic tyrosine kinaseCML.
Primary myelofibrosis marked by (2)Atypical megakaryocytic hyperplasia. Megakaryocytes leads to fibroblast proliferation and progressive replacement of marrow space by extensive collagen deposition.
PMF characterized bySplenomegaly (compensatory extramedullary hematopoiesis) and tear drop RBC/dacrocytes and nucleated RBCs.


Question Answer
Nonpolar, hydrophobic amino acids, PAM Is my ValPhe, Alanine, Methionine , Isoleucine, Valine
Nonpolar, hydrophobic amino acids form what part of G-protein coupled membrane-bound receptorsTransmembrane.
Iron containing proteins includeHemoglobin, Myoglobin, Cytochrome Oxidase. Heme is Protoporphyrin and Iron.


Question Answer
NADPH is energy butIt cannot be used to convert ADP to ATP
NADPH is active in liver, adrenals because it is needed forFA, Cholesterol and Steroid synthesis
Nonoxidative reactions of HMP shunt are used toInterconvert Robise5-phosphate to F-6-P and Glyceraldehyde-3-p.
G6PD CausesFava Beans, Specific Meds (Primaquine, Sulfa) and Infections
Ketogenesis will deactivateAcetyl-coA carboxylase, which makes Malonyl CoA and then FA.


Question Answer
Skeletal muscle carnitine deficiencyMyoglobinemia, weakness following exercise, elevted muscle triglycerides, hypoketonemia
Systemic primary carnitine deficiencyinherited defect in transport of LCFAs into the mitochondria; toxic accumulation. Causes weakness, hypotonia, and hypoketotic hypoglycemia.
MCAD/ Medium Chain Acyl-coA Dehydrogenase Deficiency presentationHypoglycemia and Hypoketonemia
Oxidation of FA leads to more or less energy per carbon atom vs carbMORE
FA B-oxidation leads to1 NADH, ! FADH2, 1 Acetyl CoA (-> 3 NADH, 1 FADH, 1 GTP)
Key enzymes in KetogenesisCAT II (Acyl Carnitine -> Acyl-CoA) and Aceyl-CoA Dehydrogenase.


Question Answer
Neurotoxicity in MUD is fromLeucine accumulation
Maple syrup smell fromIsoleucine
Some patients with MUD may improve fromDietary restriction and high dose thiamine treatment (since Thiamine is part of TLCFN for alpha ketoacid dehydrogenase reaction)
PKU is either from deficiency of PheHydroxylase ORTHB
Folic acid is frequently deficient inAlcoholics
Folic acid supplementation forTreating homocystinemia and prevention of neural tube defects
Homocysteinemia, two treatmentsB6 and B12 to try to move it along either to Methionine or to Cystathione
B6 supplementation used forSideroblastic anemia and hyperhomocysteinemia.
Krabbe diseaseGalactocerrebrosidase deficiency needed for hydrolysis of galactocerebroside, in myelin.
B6 pathwaysTransamination, decarboxylation, heme and neurotransmitter synthesis


Question Answer
Helicase vs DNAAUnwinds and DNAA identifies origin of replication
What keeps unwound DNA from re-annealingSingle-stranded DNA binding proteins/ SSB
DNA synthesis always occurs in 5’ to 3’ direction but lagging strand ...3’ to 5’ and then DNA primase and ligase join together Okazaki fragments (whereas leading strand is 5’ to 3’)
Okazaki fragments/ lagging strand formation3’ to 5’ direction; Primase puts down primers; DNAPI removes RNA primers and puts down DNA and Ligase joins them together


Question Answer
ApoA-1LCAT activation/ cholesterol esterification
ApoB48Chylomicron assembly and secretion by intestine
ApoB100LDL particle uptake by extrahepatic cells
ApoC-IILipoprotein lipase activation (defect -> Familial Hyperchylonmicronemia Type I)
ApoE-3 and 4VLDL and chylomicron remnant uptake by liver cells (defect -> Familial Dysbetalipoproteinemia Type III)


Question Answer Column 3
Vitamin C deficiency-> Impaired collagen formation/ decreased hydroxyproline and then SCURVYSUBPERIOSTEAL HEMATOMAS; bleeding into joints spaces; gingival swelling; periodontal infection; anemia; hyperkeratotic papular rashes; impaired wound healing; weakened immune responses to local infection
Vitamin C what type of reactionsHydroxylation. Ex. Activation of prolyl and lysyl hydroxylase precursors which are necessary for hydroxylation of procollagen.
Zinc deficiencyAcrodermatititis enteropathica, growth retardation and infertility
Vitamin K deficiencyBleeding diathesis/ bleeding tendency but not painful gum
B6 deficiencyCheilosis, glossitis, dermatitis and peripheral neuropathy
B2 deficiencyCheilosis, stomatitis, glossitis, dermatitis, corneal vascularization


Question Answer
PLC ->PIP2 -> IP3 and DAG.
What stimulates PKCDAG vs. IP3 increases intracellular Ca to further activate PKA


Question Answer
Pigment stones are most common inRural Asian populations and especially women and elderly
Brown pigment stones are fromInfection of biliary tract, releasing B-glucuronidase. Hydrolyzes bilirubin glucoronides and increases amount of unconjugated bilirubin in bile.
What increases risk of brown pigment stonesE. Coli, Ascaris and Liver Fluke Opisthorchis Sinensis. Ascaris – common roundworm that infects 25% of world’s population especially in areas of poor sanitation whereas C. Sinensis is endemic in China, Korea and Vietnam.
Sinenesis increases risk ofGallstones, cholangitis, cholangiocarcinoma.
Pigment stones are radioOPAQUE if Black (Ca bilirubinate, hemolysis) and LUCENT if Brown


Question Answer
Which cells cannot use ketonesErythrocytes/ RBCs since they do not have mitochondria and also hepatocytes
Ketones are typically produced inLiver
Ketones are typically used bySkeletal muscles, cardiac muscles, renal cortex, brain during starvaton


Question Answer
DHB reductase involved in what reactions in pathwayDHB reductase in Phe hydroxylase and in Tyr hydroxylase.
DHB Reductase deficiency and then DHB reductase leads toReduction in TYR, DOPA, 5HT, NO (5HT and NO via different pathways). Less Dopa and Dopamine -> Less inhibition of Prolactin release -> Increased levels of Prolactin
Epi -> NE viaPNMT and SAM.