Biochem miscellaneous Flashcards
exceptions to degeneracy of genetic code
methionine + tryptophan (each encoded by only 1 codon)
codon for methionine
AUG
codon for tryptophan
UGG
nucleotides methylated in replication
cytosine + adenine
how is uracil derived?
deamination of cytosine
what makes thymine unique?
Has a methyl grow.
when does NER occur?
G1
sequence of events in base excision repair
glycosylase removes altered base and creates AP site –> AP endonuclease cleaves 5’ end –> lyase cleaves 3’ end –> pol fills gap –> ligase seals it
significance of N-formylmethionine (fMET)
- initiates protein synthesis in bacteria.
- Nucleic acid coded by start codon.
- Stimulates neutrophil chemotaxis.
polyadenylation signal
AAUAAA
describe mRNA quality control
Occurs at cytoplasmic processing bodies (P-bodies), which contain exonucleases, decapping enzymes, and microRNAs. mRNAs may be stored in P-bodies for future translation.
what initiates protein synthesis?
GTP hydrolysis
describe trimming
removal of N- or C-terminal propeptides from zymogen to generate mature protein (eg trypsinogen –> trypsin).
labile cell types
bone marrow + gut epithelium + skin + hair follicles + germ cells
stable cell types
hepatocytes + lymphocytes
golgi functions
1) protein distribution
2) modifies N-oligosaccharides on asparagine
3) adds O-oligosaccharides on serine and threonine.
4) adds mannose-6-phosphate
Signal recognition particle (SRP)
abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER. Absent or dysfunctional SRP leads to protein accumulation in the cytosol.
examples of intermediate filaments
vimentin + desmin + cytokeratin + lamins + glial fibrillary acid proteins (GFAP) + neurofilaments
Vimentin
stains for mesenchymal tissue (eg., fibroblasts, endothelial cells, macrophages).
microvilli
microfilament
cilia structure
9+2 arrangement of microtubule doublets. Base (basal body) consists of 9 microtubule triplets with no central microtubules.
axonemal dynein
ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.
frequency of an x-linked recessive disease in males
q
frequency of an x-linked recessive disease in females
q squared
what is wrong in prader willi vs. angelmans
codebook
2 rules for inheritance chart
1) look for recessive/dominance
2) who’s passing it down (only moms –> mitochondrial inheritance)
gene mutated in myotonic dystrophy type 1
DMPK
myotonia
Delayed relaxation of skeletal muscles after voluntary contraction or electrical stimulation. Feature of myotonic dystrophy.
medical word for night blindness
nyctalopia
medical word for dry, scaly skin
xerosis cutis
medical word for corneal degeneration
keratomalacia
significance of flavins (FMN, FAD)
used as cofactors in redox reactions
relationship between isoniazid and pyridoxine deficiency
Pyroxidine’s active form is the cofactor for gamma-aminolevulinate synthase, the enzyme that catalyzes the rate-limiting step of heme synthesis
vitamins required for niacin synthesis
B2 + B6
pyridoxine used in synthesis of…
cystathionine, heme, niacin, histamine, serotonin, epinephrine, norepinephrine, dopamine, GABA
storage form of vitamin D
25-OH D3
active form of vitamin D
calcitriol, 1,25-(OH)2D3
ergocalciferol
D2, ingested from plants
cholecalciferol
D3, consumed in milk, formed in sun-exposed skin.
location of D3 synthesis
stratum basale
biochemistry of folate deficiency
Deficiency inhibits the formation of deoxythymidine monophosphate (dTMP), which limits DNA synthesis and promotes megaloblastosis and erythroid precursor cell apoptosis. Since thymidine supplementation can moderately increase dTMP levels, it can reduce erythroid precursor cell apoptosis, so need to give thymidine with folate deficiency.
other names for vitamin K
phytomenadione, phylloquinone, phytonadione
enzyme that metabolizes ethanol in microsome
CYP2E1
biochem explanation for hepatosteatosis in alcoholism
dihydroxyacetone phosphate –> glycerol-3-phosphate, which combines with fatty acids to make triglycerides leading to hepatosteatosis.
dehydrogenase action
catalyze oxidation-reduction reaction
ATP production
32 net ATP via malate-aspartate shuttle, 30 net ATP via glycerol-3-phosphate shuttle
glycerol-3-phosphate shuttle
ATP shuttle in muscle
malate-aspartate shuttle
ATP shuttle in heart and liver
what does CoA carry?
acyl groups
what does lipoamide carry?
acyl groups
What does TPP cary (thiamine pyrophosphate)?
aldehydes
glycolysis equation
FA pg 99
enzymes requiring ATP
1) hexokinase/glucokinase 2) PFK-1
where is ATP produced in glycolysis?
1) 1,3 BP –> 3-phosphoglycerate
2) PEP –> pyruvate
where is GTP produced
succinyl-CoA –> succinate
regulation by F-2-6-bisphosphate
FBP-ase (fructose bisphosphatase-2) and PFK-2 (phosphofrutokinase-2) are the same bifunctional enzyme whose function is reversed by phosphorylation by PKA.
regulation by F-2-6-bisphosphate in fasting state
increased glucagon –> increased cAMP –> increased PKA –> inceased FBPase-2 –> decreased PFK-2 –> less glycolysis, more gluconeogenesis
regulation by F-2-6-bisphosphate in fed state
increased insulin –> increased cAMP –> increased PKA –> decreased FBPase-2 –> increased PFK-2 –> more glycolysis + less gluconeogenesis
pyruvate dehydrogenase reaction
pyruvate + NAD+ + CoA –> acetyl-CoA + CO2 + NADH
positive regulation of pyruvate dehydrogenase complex
elevated NAD+/NADH, elevated ADP, elevated Ca2+
vitamins required by pyruvate dehydrogenase complex
B1-B5, except B4
tissues that rely on anaerobic glycolysis
RBCs, WBCs, kidney, medulla, lens, testes, and cornea
products of pyruvate –> acetyl-CoA
acetyl-CoA + 1 NADH + 1 CO2
products of TCA cycle
3 NADH + 1 FADH2 + 2CO2 + 1 GTP per acetyl-CoA. Thus 10 ATP/acetyl-CoA.
Where is NADH generated in TCA cycle?
1) isocitrate –> alpha-KG
2) alpha-KG –> succinyl-CoA
3) Malate –> oxaloacetate
Where is FADH2 generated in TCA cycle?
succinate –> fumarate
Where is GTP generated in TCA cycle?
succinyl-CoA –> succinate
irreversible enzymes in TCA cycle
1) PDH 2) citrate synthase 3) isocitrate dehydrogenase 4) a-KG dehydrogenase
ATP produced via ATP synthase
1 NADH –> 2.5 ATP
1 FADH2 –> 1.5 ATP
site of gluconeogenesis
primarily liver, enzymes also in kidney + intestinal epithelium.
nonoxidative reaction in HMP shunt –> enzymes required + cofactors + products
ribulose-5-P –> ribose-5-p + glyceraldehyde-3-phosphate + fructose-6-p
- via phosphopentose isomerase + transketolases
- requires B1
sucrose
glucose + fructose
treatment for hereditary fructose intolerance
decrease intake of both fructose + sucrose
triose kinase
Fructose pathway: enzyme that metabolizes glyceraldehyde –> glyceraldehyde-3-P
aldose reductase 1) action 2) where its expressed
1) galactose –> galactitol
2) glucose –> sorbitol (using NADPH)
4 epimerase
galactose metabolism: interconverts UDP-gal to UDP-Glu
sorbitol dehydrogenase
sorbitol –> sorbitol dehydrogenase (using NAD+)
pathophys of osmotic damage (cataracts, retinopathy, peripheral neuropathy) in diabetics
glucose converted to sorbitol
tissues that have both aldose reductase + sorbitol dehydrogenase
liver + ovaries + seminal vesicles
tissues that have only aldose reductase
schwann cells + retina + kidneys + lens (primarily)
essential amino acids
all amino acids coded as glucogenic + glucogenic/ketogenic + ketogenic
location of synthesis of norepinephrine, dopamine, epinephrine
NE + dopamine are produced in the CNS + PNS. Epinephrine produced predominately in the adrenal medulla.
phenylketones (detected in urine of PKU kids)
phenylacetate, phenyllactate, phenylpyruvate
describe biochem of homocystinuria
…
limit dextrin
1-4 residues remaining on a branch after glycogen phosphorlase has already shortened it.
deficiency vs. accumulated substrate in gaucher’s
glucocerebrosidASE deficiency; glucocerebroside accumulation
explain why ketone bodies build up in DKA and prolonged starvation
oxaloacetate is depleted for gluconeogenesis. This causes a build-up of acetyl-CoA, which shunts glucose and FFA toward the production of ketone bodies.
explain why ketone bodies build up in alcoholism
excess NADH shunts oxaloacetate to malate. This causes a buildup of acetyl-CoA, which shunts glucose and FFA toward the production of ketone bodies.
energy source during fasting state
Glycogenolysis is the primary source; also gluconeogenesis + adipose release of FFA.
LCAT
lecithin-cholesterol acyltransferase. Esterifies 2/3 of plasma cholesterol into cholesteryl ester (more hydrophobic form that is then sequested into the core of a lipoprotein particle). This forces newly synthesized HDL spherical and forcing reaction to become unidrectional.
exonucleases vs. endonucleases
Exonucleases remove base pairs, endonucleases cleave phosphodiester bonds within polynucleotide chains.
Folate deficiency labs
Methmalonic acid normal + homocysteine elevated.
Mucopolysaccharidoses
Hurler’s + hunters
Location of heme synthesis
1st 2 steps in mitochondria, 4 steps in cytosol, final 3 steps in mitochondria
heme synthesis pathway
succinyl-CoA + glycine –> delta-aminolevulinic acid –> porphobilinogen –> hydroxymethylbilane –> uroporphyrinogen –> coproporphyrinegen –> protoporphyrinogen –> protoporphyrin –> heme
polyadenylation vs. capping
5’ end is capped, 3’ end is cleaved off, then polyadenylated
ketogenesis.
Think of DKA. Body breaks down fatty acids to produce ketone bodies. This process supplies energy to certain organs (particularly the brain) under circumstances like fasting.
DM1 HLA association
DR3 and DR4
Insulin sensitivity in DM1
High
glucose intolerance in DM1
Severe
serum insulin level in DM1
low
Genetic predisposition in DM1
Relatively weak (50% concordance in identical twins), polygenic.
genetic predisposition of DM2 vs. DM1
DM2 relatively much stronger than DM1
genetic predisposition of DM2
Relatively strong (90% concordance in identical twins), polygenic.
HLA type DM association
None
Glucose intolerance in Type 2DM
Mild to moderate
Labs in DKA
Hyperglycemia + increased hydrogen ions + decreased HCO3 + increased blood ketone + leukocytosis + HYPERKALEMIA.
DKA treatment
IV fluids + IV insulin + K+ + glucose if necessary to prevent hypoglycemia.
Amino acids necessary for purine synthesis:
o Code: Spartin gagging out peter strand + fat sailor masturbating /GAG glycine + aspartate + glutamine. Massive wooden cat overhead/purine synthesis.
o Location: entrance to pool area
Basic positively charged amino acids
o Code: giant cat + pirate with terrible head + Edward Norton on the couch/arginine + lysine + histidine. Huge pirate in middle/arginine is most basic. Cat floating in pool of water in front of TV/histidine has no charge at body pH.
o Location: TV area
Acidic negatively charged amino acids:
Code: Spartin doing acid + fat sailor doing acid/aspartic acid + glutamic acid. Electrical wires from ceiling zapping them/negatively charged at body pH.
Location: His bedroom
Hydrophobic amino acids
o Coded character: Alan in corner + val in middle around stripper pole + Lucy in a block of ice + methhead in right corner + mike O’connell /hydrophobic amino acids = valine, alanine, isoleucine, methionine, and phenylalanine. /these amino acids compose the transmembrane domains of signaling proteins.
o Location: Hottub
glycogenic and ketogenic amino acids
o Code: lucy in a block of ice + pale and pasty Mike O’connell on top + a big turkey + theon greyjoy feasting on the turkey/isoleucine + phenylalanine + threonine + tryptophan.
o Location: Area between ketogenic and glucogenic area
glycogenic amino acids
o Code: Cuppola made of candy/glucogenic amino acids. Val stripping around pole + meth head + cat dancing/methionine (Met) + valine (Val) + histidine (his).
o Location: Patio
Describe G protein mechanism
Ligand activates the receptor —> inducing conformational change –> GDP exchanged for GTP –> Galpha subunit dissociates –> Galpha has downstream effects.
Termination –> Ga subunit hydrolyzes GTP to GDP, allowing it to re-associate with Gby and start a new cycle.
GTPase
hydrolase that binds and hydrolyzes GTP
G protein regulation
When they are bound to GTP, they are activated, and when bound to GDP, they are ‘off.’ Thus,
Amino acid type found in proteins…
Only L
Vimentin staining tumors?
Mesenchymal tumors + endometrial carcinoma + renal cell carcinoma + meningiomas.
Fuel use in exercise – when do you deplete ATP by? creatine phosphate? anaerobic metabolism?
Stored ATP depleted in 2 seconds.
Creatine phosphate rises and is depleted by 10 secs.
Anaerobic metabolism depleted by 1 min.
Myotonic type 1 Muscular dystrophy pathophys
CTG trinucleotide repeat expansion in the DMPK gene leads to abnormal expression of myotonia protein kinase.
Permanent cell types
Neurons
Skeletal and cardiac muscles
*RBCs
stable vs permanent vs labile cell types
FA 58
