Biochemistry Flashcards
Respiratory acidosis:
a. pH (up/down)
b. pCO2 (up/down)
c. HCO3- compensation (up/down)
a. pH down
b. pCO2 up
c. HCO3- up with renal compensation
Respiratory alkalosis:
a. pH (up/down)
b. pCO2 (up/down)
c. HCO3- compensation (up/down)
a. pH up
b. pCO2 down
c. HCO3- down with renal compensation
Metabolic acidosis:
a. pH (up/down)
b. pCO2 compensation (up/down)
c. HCO3- (up/down)
a. pH down
b. pCO2 down with respiratory compensation
c. HCO3- down
Metabolic alkalosis
a. pH (up/down)
b. pCO2 compensation (up/down)
c. HCO3- (up/down)
a. pH up
b. pCO2 up with respiratory compensation
c. HCO3- up
Causes of respiratory acidosis
Respiratory depression
Pulmonary disease
Causes of respiratory alkalosis
Hyperventilation
Causes of metabolic acidosis
Diabetes
Renal failure
Methanol poisoning
Causes of metabolic alkalosis
Prolonged vomiting
Nasogastric suction
Antacids
Anion gap calculation
AG = Na - (HCO3 + Cl)
Normal = 12 +/- 4 mEq/L
What happens to anion gap in acidosis?
HCO3- is consumed (decreased). Anion gap increases.
How is RNA different to DNA?
U instead of T
What is a thalassemia?
Thalassemia = imbalance in Hb structure production. Must be 2 alphas and 2 beta in Hb
Sickle cell mutation
Glut -> Val
Position 6 in beta-globin chain
SSx of sickle cell disease
Hemolytic anemia
Sickle cell crises: severe pain in bones, chest, abdomen, often triggered by dehydration or infection
Tx for sickle cell disease
Hydroxyurea
MOA here = boosts Hb F (gamma-globin) expression.
Hb C disease mutation
Glut -> Lys
Position 6 in beta-globin chain (same as sickle cell dz)
SSx of Hb C disease
RBCs form crystals = mild to moderate hemolytic anemia
No episodic crises as in sickle cell disease
Occasional abdominal pain (splenomegaly, cholelithiasis)
Hb E disease mutation
Glut -> Lys
Position 26 in beta-globin
In what group is sickle cell and Hb C disease prevalent?
Africans, West African
In what group is Hb E disease prevalent?
Southeast Asian
SSx of Hb E disease
Mild thalassemia as beta-globin chain not synthesized effectively
Microcytosis, hypochromia, not significant or only very mildly anemic. Typically incidental finding.
CF inheritance
AR
Defect/pathogenesis in CF
Defect in CFTR gene encoding chloride channel
Mutation in Phe residue at position 508. Interferes with protein folding and glycosylation.
HD inheritance
AD
Pathogenesis in HD
CAG TNR repeat
Contains long stretches of glutamine residues. Misfolded protein aggregates in nuclei of neurons.
Imaging findings in HD
Lateral ventricle enlargement
Double reciprocal plot (aka Line-Weaver Burk) axes
X-axis: 1/[S]
Y-axis: 1/[v]
Where line intercepts with y-axis = 1/Vmax
Where line intercepts x-axis = -1/Km
Vmax
Max rate of product formation by enzyme
Vmax or Km is dependent or independent upon enzyme concentration?
Vmax is dependent upon enzyme concentration. Explained: more enzyme = higher rate of conversion to product.
Km is independent of enzyme concentration. Reflects physical properties of individual enzyme molecules.
Km
Inversely related to the affinity of the enzyme for its substrate.
Km = 1/2 Vmax
What will increasing concentration of inhibitor look like on a double reciprocal plot?
Increasing steepness of line = increased [inhibitor}
What does reversible competitive inhibition look like on a double reciprocal plot? Describe changes to Km and Vmax.
Mnemonic = competitive scissors
Inhibitor and substrate compete for binding at same active site
Multiple lines of increased inhibitor concentration on plot with all lines going through same point on y-axis
Km: apparent Km increase
Vmax: unchanged
What does reversible noncompetitive inhibition look like on a double reciprocal plot? Describe changes to Km and Vmax.
Inhibitor and substrate compete for binding at the active site
Multiple lines of increased inhibitor concentration on plot with all line going through different points on y-axis, arising from same point on x-axis.
Km: apparent Km unchanged
Vmax: decreased
What does irreversible inhibition look like on a double reciprocal plot?
Same as for reversible non-competitive inhibition.
This is covalent modification of active site residue. Like you are taking enzyme out of the reaction. Difference = cannot wash or dilute the irreversible inhibitor out, whereas you can wash away the non-competitive inhibitor.
Aspirin
Irreversible PG synthase inhibitor
Ibuprofen
Competitive inhibitor of PG synthase
Inhibitors of EF-2
Diphtheria toxin and pseudomonas exotoxin A
These ADP-ribosylate EF-2
Inhibitors of 60 S subunit via removing adenine bases from 28s rRNA
Ricin, Shiga toxin
Prenylation
Links G-proteins to hydrophobic residues in cell membrane
Statins interfere with this
I cell disease
Defect in phosphorylation of mannose residue on enzyme directed to lysosome that is supposed to degrade molecules there. See accumulation of molecules in lysosome.
Ways in which DNA is silenced/imprinted
DNA methylation &
Histone deacetylation
What do PPAR transcription factors regulate?
Regulate lipid metabolism
What transcription factor regulates immune system response?
NFkappaB
What transcription factor regulates development and patterning in utero?
Homeodomain proteins (HOX)
PEP carboxykinase
Where does this enzyme function?
Gluconeogenesis
PEP carboxykinase
How is it expression of this stimulated?
Cortisol stimulates expression via cortisol receptor (nucleus)
Glucagon binds to membrane receptor and induces expression via cAMP/CREB
Epi binds to G-protein inducing expression
Examples of water soluble hydrophilic hormones
Insulin, glucagon, epinephrine, oxytocin
Examples of lipid soluble hormones
Steroid hormones, calcitriol, retinoic acid, thyroxine
Describe activation of adenylate cyclase and downstream cascade
Heterotrimeric G protein (alpha subunit, beta, gamma)
Alpha subunit binds GTP and dissociates from beta, gamma
Alpha subunit activates adenylate cyclase = cAMP
cAMP activates PKA
PKA activates phosphorylase kinase
Phosphorylase kinase converts phosphorylase b into phosphorylase a, which is more active
Describe phospholipase C second messenger system activation and downstream cascade
Hormone binds G-protein, which interacts with PLC
PLC cleaves PIP2 in membrane, generating IP3 and DAG (remains anchored into PM)
IP3 binds to receptor at endoplasmic reticulum inducing release of Ca
DAG + Ca activate protein kinase C
Protein kinase C regulates metabolic enzymes and control of gene expression
Calcium has other signaling roles
Thiamine (B1) function
Decarboxylation of alpha-ketoacids (enzymes = pyruvate DH, alpha-ketoglutarate DH and branched-chain alpha-ketoacid DH)
Transketolase rxn (PPP)
Thiamine deficiency disorders
Beriberi
Wernicke’s encephalopathy
Beriberi
Deficiency?
SSx?
Deficiency in B1
SSx: pain, paresthesias, impaired cardiac energy metabolism, peripheral edema, peripheral neuritis, symmetric peripheral neuropathy
Wernicke encephalopathy
Deficiency?
SSx?
Deficiency in B1
SSx: horizontal nystagmus, ophthalmoplegia, cerebellar ataxia, mental impairment
Riboflavin (B2) function
Required for dehydrogenases needed to produce FAD
SSx of riboflavin deficiency
Mucocutaneous involvement: smooth, swollen, magenta/red tongue, stomatitis, cheilosis
Niacin (B3) function
Required for dehydrogenases needed to produce NAD and NADP
Deficiency of niacin
Pellagra
Pellagra
Deficiency?
SSx?
Deficiency in niacin
SSx: 4 Ds - dermatitis, diarrhea, dementia, death
From what AA can niacin be synthesized?
Tryptophan. This requires B6.
Pyridoxine (B6: Pyridoxal phosphate) function
Enzymes of AA metabolism
Heme synthesis (delta-aminolevulinate synthase)
Deficiency of pyridoxine (B6)
Overlaps niacin deficiency (as it is used to convert tryptophan to niacin). Niacin deficiency = 4 Ds (dermatitis, dementia, diarrhea, death)
+
Heme synthesis impairment (sideroblastic anemia)
