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Biochemistry Flashcards

1
Q

Acetaminophen toxicity causes alteration of what metabolite in hepatocytes causing jaundice, inc PTT and inc AST?

A

Decrease in glutathione (antioxidant that eliminates free radicals) - think glutathione goat!
NADPH (by-product of G6PD) regenerates reduced glutathione

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2
Q

If there is a defect in renal ammoniagenesis (NH3), what substrate is the most likely source of ammonia production?

A

glutamine

Produces 2 NH4(+) and 2 HCO3(-) for each glutamine metabolized

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3
Q

Abnormal storage of lipids in nerve cells of CNS and PNS. Neurodegeneration, seizures, coarse facies, skeletal deformities, contractures of large joints. Dx?

A 
GM1 gangliosidosis (deficiency in b-galactosidase)
Abnormal targeting of lysosomal enzymes to lysosomes
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4
Q

Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins

A

Proteasome

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5
Q

Membrane-enclosed organelle that catabolises very-long-chain FA through b-oxidation, branched-chain FA, aa, and ethanol

A

peroxisome

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6
Q

Not all individuals with a mutant genotype show the mutant phenotype

A

Incomplete penetrance

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7
Q

One gene contributes to multiple phenotype effects

A

pleiotrophy

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8
Q

Phenotype varies among individuals with the same genotype

A

variable expressivity

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9
Q

Mutation process that occurs during DNA replication. Denaturing and displacement of DNA stands resulting in mispairing of the complementary bases

A

Slipped strand mispairing (SSM)

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10
Q

MCC of thiamine deficiency developed and developing countries.

A

Developing - white rice

Developed - alcoholism

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11
Q

Thiamine def can present as?

A

Wet beriberi (dilated cardiomyopathy)
Dry beriberi (polyneuropathy)
Mammillary body degeneration (Wernicke-Korsakoff syndrome)
Note: Wernicke encephalopathy is caused by lesions in the medial thalamic nuclei, mammillary bodies, periaqueductal and periventricular brainstem nuclei, and superior cerebellar vermis

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12
Q

What do these conditions have in common?

Ataxia-telangiectasia, xeroderma pigmentosum Fanconi anemia, Bloom syndrome, HNPCC

A

Deficient DNA-repair enzymes

G2 of cell cycle

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13
Q

Photosensitive dermatitis, diarrhea, dementia - caused by a deficiency in what vitamin?
What enzymes in the TCA cycle are dependent on this vitamin?

A

Pellagra- niacin (B3) def
Niacin is a precursor for NAD and NADP
- isocitrate dehydrogenase, a-ketoglutarate dehydrogenase, malate dehydrogenase, pyruvate dehydrogenase

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14
Q

What role does the ubiquitin-proteosome pathway play in the immune response?

A

Degrades foreign intracellular proteins which are then coupled to MHC

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15
Q

Primary hemolytic anemia is associated with defects in what 2 pathways? What classic condition causes this?

A
  1. Glycolysis
  2. Hexose monophosphate shunt
    - these paths make energy and antioxidant defense for RBC

Dx - pyruvate kinase def (AR)!!! –> red pulp hyperplasia of spleen d/t inc work of splenic parenchyma to removed deformed erythrocytes

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16
Q

How does maternal use of TMP-SMX cause kernicterus?

A

TMP-SMX binds albumin, displacing bilirubin

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17
Q

Antibiotics, anticonvulsants and anti-tb drugs interfere with what vitamin in breast milk? What biochemical process is subsequently hindered?

A

Vit K

- can’t form gamma-carboxyglutamate residues –> hemorrhagic disease of the newborn

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18
Q

Deficiency in what vitamin is responsible for ecchymoses on the extremities and hemorrhages around hair follicles in an alcoholic?

A

Vitamin C (Scurvy)

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19
Q

Infant with recurrent vomiting and diarrhea with yellow sclera, opacity in lens, and swollen abdomen. What dietary incompatibitliy may have caused this?

A

Classical galactosemia - def of galactose-1-phosphate uridyltransferase
Tx - Avoid lactose

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20
Q

In DKA, how does the level of 3-hydroxybutyrate compare to acetoacetate?

A

Increase in 3-hydroxybutyrate is ~5x higher than the inc in acetoacetate
(decreased acetoacetate:3-hydroxybutyrate)

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21
Q

Rubber-like properties of elastin are due to what?

A

Cross-linking between elastin monomers (lysine), which is facilitated by lysyl oxidase.

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22
Q

During bacterial DNA replication, what removes RNA primers via 5’ to 3’ exonuclease activity and replace them with DNA (via 5’ to 3’ polymerase activity)?

A

DNA polymerase I

Note: both DNA pol I and III have 3’ –> 5’ exonuclease activity

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23
Q

Sickle cell anemia is due to glutamic acid (hydrophilic) substitution for what?

A

Valine (hydrophobic) - abnormal sequence of beta chain of hemoglobin (position 6)

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24
Q

HbC is caused by what type of mutation?

A

Missense mutation (glutamate substituted by lysine in the beta globin chain)

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25
Why is F1P (from metabolisim of fructose) so rapidly metabolized in the glycolytic pathway?
Bypasses PFK-1, the major rate-limiting enzyme of glycolysis
26
hydroxylation of proline and lysine residues in collagen synthesis occur where?
RER
27
Cause of maturity-onset diabetes
mutations in glucokinase gene (glucose sensor in pancreatic beta cells and control rate of glucose entry into the glycolytic pathway)
28
Ehlers-Danlos is caused by impaired collagen synthesis due to lack of what?
Procollagen peptidase deficiency (N-terminal propeptide cannot be removal extracellularly)
29
Homeobox genes encode what?
DNA-binding transcription factors - important for segmental organization of the embryo along the cranio-caudal axis
30
When a pair of alleles are inherited together in the same gamete more often or less often than expected given random pairing
linkage disequilibrium
31
alpha helices in a protein receptor are for what purpose?
anchoring it to the cell membrane (eg G protein coupled receptor) has hydrophobic aa (alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, methionine, proline, glycine)
32
Bonds stabilizing primary protein structure
peptide bonds (between aa)
33
Bonds stabilizing secondary protein structure
Hydrogen bonds
34
Bonds stabilizing tertiary structure
Ionic, hydrophobic, hydrogen, disulfide. Note: disulfide bonds are very strong covalent bonds bw 2 cysteine residues that enhance proteins ability to withstand denaturing
35
Fatty streaks are the earliest lesions of atherosclerosis and the primary cells are what?
macrophages (foam cells)
36
What proteins are able to bind DNA?
``` Transcription factors (eg N-myc, C-myc) steroids thyroid proteins Vit D receptors retinoic acid receptors DNA transcription and replication proteins ```
37
In specialized transduction, the genes transferred by the virus to the new bacterium are always genes located where?
located closest to the insertion site of the virus Note - specialized transduction = transfer of genes from 1 bacterium to another as an accident of the life cycle of a temperate phage.
38
Alcoholism can cause deficiency in what vitamin, which can cause what symptoms?
Thiamine deficiency | Sx - wet and dry beriberi; wernicke korsakoff; pyruvate dehydrogenase, transketolase deficiency
39
What techniques can be used to analyze a patient's fragile X syndrome carrier status?
1. PCR - primers amplify the fragment with the CGG repeats | 2. FMR1 analysis by Southern blotting (allows size and repeat segment and methylation to be assayed simultaneously)
40
An HFR to F- cell conjugal cross begins with a break at ___ and then chromosomal genes transferred in order with ___ being last
oriT first | tra last
41
What enzyme is an RNA-dependent DNA polymerase (reverse transcriptase) that adds TTAGGG repeats to the 3' end of chromosomes?
Telomerase - found in stem cells
42
An abdominal mass showing cells w/highly developed smooth ER, likely get stimulated from what agent?
ACTH | Smooth ER contains enzymes for steroid and phospholipid biosynthesis.
43
In a patient with acidic urine, which amino acid is most important for maximizing acid excretion?
Glutamine (becomes glutamate, which is needed to generate ammonium via transamination)
44
Glucose is converted into sorbitol by what? Sorbital is then converted into what by sorbitol dehydrogenase?
1. aldolase reductase 2. Fructose (note: hyperglycemia can cause sorbitol accum in tissues with lower sorbitol dehydrogenase activity like retina, lens, kidney, and peripheral nerves)
45
What protein binds to a ribosome when it encounters a stop codon?
Release factor 1
46
KRAS genes produce Ras protein. This protein is only active when bound to what substance?
GTP | Regulation of Ras-MAPK signal transduction path requires balance bw GTP-bound and GDP-bound Ras proteins.
47
Differentiate NADPH oxidase and superoxide dismutatse
Opposites NADPH oxidase - forms free radicals to aid in bacterial destruction Superoxide dismutase - neutralizes reactive oxygen species, preventing cell injury
48
What substance is responsible for inhibiting b-oxidation of FA in the well-fed state?
malonyl-coA (inhibits mito carnitine acyltransferase)
49
How is the lac operon in e coli positively and negatively regulated?
Positive: cAMP-CAP binding upstream from promoter region Negative: binding of repressor protein to the operator locus (continuous expression of lac operon genes is d/t mutations that impair binding of Lac I repressor protein)
50
What type of DNA exists as a small circular chromosome?
Mitochondrial DNA - MC non-nuclear DNA in eukaryotes
51
c-Jun proteins are most likely to be detected on what type of blot?
Southwestern - detects DNA-binding proteins c-Jun and c-Fos are nuclear transcription factors that directly bind DNA via leucine zipper motif Other DNA-binding proteins include transcription factors, nucleases and histones
52
What is the function of the TATA box?
promoter region that binds transcription factors and RNA pol II during initiation of transcription. Located 25 bases upstream from start of coding region
53
NADPH from HMP shunt is used for what other processes?
Reducing glutathione | Biosynthesis of cholesterol, FA, and steroids
54
Alcoholism inc NADH/NAD ratio causing what?
``` Favors glycolysis Impairs pathways requiring NAD+ Pyruvate --> lactate; OAA --> malate DHAP --> glycerol-3p Dec FA oxid, ketones, impaired gluconeogenesis (inhibits malate --> OAA) ```
55
Where is ACE produced?
lungs | Will see inc ATII in pulm vein compared to pulm a
56
osteocytes of the bone remain connected to each other by what?
gap junctions - send signals to and exchange nutrients and waste with the osteocytes within neighboring lamellae. Also sense mechanical stress and regulate bone remodeling
57
Nitric oxide is synthesize from what amino acid?
Arginine via NO synthase. | Arginine supplementation may play an adjunct role in tx of conditions that improve with vasodilation (eg stable angina)
58
Order of base excision repair
``` Glycosylase - cleaves altered base Endonuclease - cleaves 5'end lyase - cleaves 3'sugar phosphate DNA polymerase - fills single nucleotide gap Ligase - seals nick ```
59
Vast majority of Down synd cases arise due to nondisjunction during maternal meiosis ___?
one
60
P bodies
P bodies are in cytoplasm of cell and store mrna. Involved in mrna reg and turnover
61
differentiate base excision repair from nucleotide excision repair
Base excision - glycosylases remove abnormal base (spontaneous or secondary to chemical exposure) Nucleotide excision - endonuclease nicks damaged strands on both sides (eg UV damage)
62
Proteins destined for the lysosome require what to ensure proper transit through the Golgi?
Phosphorylation of specific mannose residues
63
In mm contraction, Ca binds to what, removing what so myosin cross-bridge ADP phosphate complex can bind to actin?
Ca binds to TROPONIN --> tropomyosin removed | Note: Ca is responsible for increasing reaction rate during active contraction
64
ATP is required for what part of mm contraction?
Myosin head detachment from the actin filament
65
How else can you produce NAD+ if you are deficient in Niacin?
Synthesized endogenously from Tryptophan or nicotinamide
66
Splicing is performed by spliceosomes, which remove introns containing _ _ at the 5' splice site and _ _ at the 3'splice site
5' GU | 3' AG
67
What do the following ribosomes make? 1. RER 2. SER 3. Free ribosomes
1. RER - cell membrane proteins, secretory proteins, proteins in ER, Golgi and lysosomes 2. SER - Steroid hormone, drug detox 3. Free ribosomes - cytosolic, nucleosol, peroxisome, and nuclear-encoded mito proteins.
68
Stop codons
UAA, UAG, UGA
69
How is glycogen degradation synchronized with skeletal mm contraction?
Sarcoplasmic ca inc causes activation of PHOSPHORYLASE KINASE --> stim glycogen phosphorylase to inc glycogenolysis
70
Short non-coding RNA seq that induces posttranscriptional gene silencing
RNA interference. | siRNA and microRNA are involved and base-pair with complementary sequences within target mRNA molecules
71
Glutamine and glutamic acid abbreviations
Gln - glutamine | Glu - glutamic acid
72
Barr bodies are condensed bodies composed of heavily methylated DNA found at the periphery of the nucleus. This region of DNA is most likely assoc with what genetic findings?
Low transcription activity (X-inactivation)
73
Zinc-finger motifs are used by TRANSCRIPTION FACTORS to bind DNA and alter activity of target genes. INTRACELLULAR receptors that bind what contain these zinc-fingers?
Steroids Thyroid hormone fat-soluble vitamins These act directly as transcription factors
74
What processes occur in the cytosol? Mitochondria?
Cytosol - glycolysis, FA synthesis, HMP shunt | Mito - B oxidation of FA, TCA, gluconeogenesis, oxid phosphorylation
75
What are symptoms of vit D intoxication? What conditions presents similarly?
Sx - mental status change, mm weakness, constipation, polyuria/polydipsia. Sarcoidosis presents similarly - activated macrophages in sarcoidosis and other granulomatous diseases express 1-a-hydroxylase --> excess 1,25 dihydroxyvit D and hypercalcemia
76
Lactic acidosis in septic shock results from tissue hypoxia, which impairs what?
Oxidative phosphorylation and causes shunting of pyruvate to lactate following glycolysis. Dec bicarb and inc AG are indicative of AG metabolic acidosis secondary to elevated lactic acid level
77
Alcoholism causes megaloblastic anemia by depleting what?
Folate - depletion can occur in months (FASTER) | Note: B12 can also cause this, but depletion takes years
78
Glycosylation of proteins occurs where in the cell?
Inside the RER
79
What following class of drug receptors is most likely to trigger the fastest measurable physiologic response? - G protein coupled receptor - Intracellular steroid receptor - Ligand-coupled ion channel receptor - Receptor tyrosine kinase
Ligand coupled Note: Intracellular--takes time for transcription, GPCR has to go through a secondary cascade in order to activate transcription (ie. cAMP--PKA--activity, etc.) Same for receptor tyrosine kinases. Ligand coupled ion channels would instantly be activated and can for instance cause depolarization/hyperpolarization--immediate effects. 
80
Homologous pairing of chromosomes in prophase I is essential for what normal process?
Crossing over - chromosome exchange of segments during meiosis I
81
Leg in a cast results in dec calf size over time. MOA?
Muscle atrophy d/t inc PROTEIN degradation and down reg of protein synthesis
82
What is the function of ribosome peptidyl transferase?
forms peptide bonds (COVALENT bonds) between adjacent amino acids using tRNAs during the translation process of protein biosynthesis.
83
What would be prevented if the kinase portion of tyrosine kinase receptors were defective?
The direct downstream processes are effected - failure to autophosphorylate (failure of phosphorylation of downstream molecules via the kinase cascade is attached to the receptor)
84
What type of polymerase does HIV use?
RNA-dependent DNA polymerase | Note: DNA-dependent DNA polymerases are usually found in regular transcriptional processes
85
Why do mitochondria encode their own tRNA?
The use a non-standard genetic code Mitochondria carry their own DNA [mtDNA]. The info stored in the mtDNA is used to produce several of the enzymes essential to make ATP. Mutations in the mtDNA that cause the mito to fail/function improperly --> risk for a number of disorders, including Leigh's disease. Leigh's disease: crucial cells in the brain stem have mutated mtDNA, creating poorly functioning mito --> chronic lack of energy in the cells, which, in turn, affects the CNS and inhibits motor functions.
86
Dysfunction of a protein that controls the trafficking of vesicles INTO the Golgi does what to the RER?
Dilates the RER - COP II if stuff not going to golgi, then it will accumulate in the RER --> dilation. This is bc normally whenever a protein is made in RER, it goes down to golgi for packaging.
87
What organ beside the liver can produce a modest amount of gluconeogenesis? (eg a patient runs out of liver glucose stores when running a marathon uses what other organ to make glucose?)
Kidney Note: In mammals, gluconeogenesis is restricted to the liver, the kidney and possibly the intestine. However these organs use somewhat different gluconeogenic precursors. The liver uses primarily lactate, alanine and glycerol while the kidney uses lactate, glutamine and glycerol.
88
process by which various macromolecules are transported across the interior of a cell. Vesicles are employed to intake the macromolecules on one side of the cell, draw them across the cell, and eject them on the other side.
Transcytosis - eg epithelial cells, blood capillaries, neurons, osteoclasts, intestinal cells, antibodies
89
The binding of a ligand to a memb-bound receptor can result in a conformational change in the receptor --> activation of an enzyme like AC. This conformational change is initiated by a series of events that requires the binding of what nucleotide?
GTP GTP is essential to signal transduction, particularly with G-proteins, in second-messenger mechanisms where it is converted to GDP (guanosine diphosphate) through the action of GTPases.

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