Biochem facts Flashcards
Amino acids necessary for purine synthesis?
GAG
Glycine
Aspartate
Glutamine
What drugs inhibit enzymes of pyrimidine syn;
Ribonucleotide reductase
Thymidalate synthase
DHFR
RR= Hydroxyurea TS= 5FU DHFR= MTX, TMP, Pyrimethamine
What drugs inhibit purine synthesis?
6-MP
Azathiprine
Ribavirin
Mycophenalate mofetil
Only two amino acids that are coded by only 1 codon?
Methionine
Tryptophan
DNA replication enzyme functions: Topoisomerase DNA pol 3 DNA pol 1 Telomerase
Topo =Relieve supercoils
DNApol3= 5->3 synthesis & 3->5 Exonuclease
DNA pol1= Degrades RNA primer and replaces it with DNA
Telomerase= adds DNA 3’ ends of chromosomes to avoid loss during duplication
Enzyme responsible for replacing RNA primers during DNA replication?
DNA pol 1
Enzyme that has proofreading capabilities during DNA replication?
DNA pol 3
3->5 EXOnuclease
Transition vs Transversion mutation?
BOTH Missense or nonsense mutations
Transition= replace purine with purine (opposite also true)
Transversion= Purine with pyrimidine
Nucleotide excision repair?
Endonuclease release damaged Bases and DNA pol & Ligase fill in gaps
What disease is caused by defective Endonuclease action?
XP ==> Cant fix Thymidine dimers in the MIDDLE of the DNA (hence ENDOnucelase)
Base excision repair?
Glycosylase removes damaged bases
Endonuclease cuts DNA
Gaps filled in by DNA pol & Ligase
What disease is caused by defective mismatch repair genes?
HNPCC=> so with every new duplication DNA mistmatches are not recognized and repaired.
What disease is caused by mutation in the repair of Double stranded breaks?
Ataxia telangiectasia
DNA repair gene mutation
In Eukaryotes what forms:
rRNA
mRNA
tRNA
DNA pol 1
DNA pol 2
DNA pol 3
**Numbered according to use of RNA during protein synthesis
**1 RNA pol makes ALL 3RNA in prokaryotes
Amanitin/ mushroom poison inhibits what?
DNA pol 2 ==> mRNA synthesis
Autoantibodies against snRNPs are highly specific of what disease?
SLE ==> aka Anti-smith antibodies
Anti-U1 RNP = mixed CT disease
Where do AAs bind on the tRNA?
3’ CCA site
What antibiotics bind the 30s and inhibit initiation complex formation?
Aminoglycosides
Antibiotics that block aminoacyl tRNA from entering acceptor site?
Tetratcyclines
Antibiotic that inhibits peptidyl transferase?
Chloramphenicol (binds 50s)
Antibiotics that prevent release of unchanged tRNA and thus inhibit translocation?
Macrolides
What two signals inhibit G1->S phase transition?
p53
Hypophosphorylated Rb
Examples of:
Permanent cells
Stable
Labile
Permanent-= RBC, neuron, skeletal/ cardiac m Stable = hepatocyte labile= BM, skin, gut epithelium
What is the site of N-linked oligosaccharide addition to proteins?
RER
**Nissel bodies in neuron= RER
Functions of SER?
Steroid synthesis
Detoxification
**Hepatocytes + Adrenal cortex rich SER supply
What adds 0-oligosaccharides on serine residues and mannose-6P to proteins?
GOLGI
I cell disease
Features of I cell disease?
Enzymes secreted into ECS not lysosomes
Coarse face
CLouded cornea
Gingival hyperplasia
What is the function of signal recognition particles?
Traffic proteins from ribosomes to RER by recognizing hydrophobic regions.
**Defect= accumulation of proteins in cytosol
Cis vs Trans golgi?
Cis=> closer to RER
Trans=> sends vesicles to plasma membrane
Pt with recurrent pyogenic infections, light colored skin, and neuropathy has defect in what process?
Chediak Higashi = mutation in lysosomal trafficking regulator gene required for Microtubule dependent sorting of proteins into vesicles
What drugs act on microtubules?
Mebendazole Griseofulvin Vincristine Paclitaxel Colchicine
What elements are required for microvilli, muscle contractions, “Cytokinesis”, adherens junctions?
Actin and myosin
What structures composeL Desmin vementin Cytokeratin Lamins GFAP
Intermediate filaments
What is made by collagen: Type 1 Type 2 Type 3 Type 4
T 1 = Bone, tendons, ligaments, scar, cornea, dentin
T2= Cartilage, nucleus pulposus
T3= Skin, BVs, Granulation tissue
T4= basement membrane
Collagen production:
Inside fibroblast RER
Outside fibroblast
Inside RER= Gly-x-y synthesis, Hydroxylation, Glycosylation, Triple helix
outside = Peptide cleavage, Cross links (Cu dep)
What part of collagen production requires Vitamin C and Cu?
Vit C= Hydroxylation
Cu = Cross linking hydroxylysine residue
Features of Alports syndrome?
Defect in T4 collagen X-linked
Nephritis
Deafness
Ocular issues
What are features of Elastin?
Rich in proline and glycine NONhydroxylated
Cross linking makes it Elastic
Wrinkles= dec collagen & elastin
Def in Marfans and Emphysema
Direct vs Indirect ELISA?
Indirect= Find Specific antibodies in pt serum using test antigen Direct= find Antigen in pt serum using antibody
What test is able to detect SNPs and genetic linkages?
Microarrays
Phenotypes vary among individuals with same genotype?
Variable expressivity
One gene contributes to multiple phenotypes?
Pleiotropy
Mutation at different sites produce similar phenotypes?
Locus heterogeneity = Albinism
Different mutation in the same site produce same phenotype?
Allelic heterogeneity = Beta thalasemia
Associations with ADPKD?
Ch 16
Berry aneurysms
MVP
Pt with telangiectasia, epistaxis, skin discolorations, and CT scan shows SAH?
Osler-Weber- Rendu
Blood vessel disorder=
AVM leading to SAH
NT changes seen in Huntingtons?
Dec ACh + GABA
What is the defect in CF?
Defect in ATP-gated Cl channel
508 Phe deletion causing abnormal folding of CFTR leading to protein retained in RER
**N-acetylcystein loosens mucus
Meiosis 1 vs 2 nondisjunction?
M1= Heterozygote M2= homozygote
Water soluble vitamins: B1= B2= B3 B5 B6 B7 B9 B12 Ascorbic acid
B1= Thiamine B2= Fiboflavin B3= Niacin B5= Pantothenic acid = CoA B6= pyridoxine B7= Biotin B9= Folate B12= Cobalamin Ascorbic acid= Vit C
What vitamin is needed for FA synthase?
B5 pantothenate= essential for CoA
**required for FA synthesis
What molecules carry: Carbon groups (CO2) 1-carbon units Methyl group Aldehyde
Biotin = CO2 THF= 1 carbon SAM= methyl Pyridoxin = Aldehyde
What is NADPH made by the Pentose phosphate shunt used?
Anabolic processes (Cholesterol, FA)
Respiratory burst
P450
Glutathione reductase
Hexokinase or glucokinase:
Induced by Insulin
Feedback inhibition by G6P
Mutated in Maturity onset Diabetes of young
Glucokinase induced by insulin
Hexokinase inhibited by G6P
Glucokinase mutated in MODY
Pyruvate dehydrogenase complex requires what cofactors? What other enzyme has the same requirements?
Pyrophosphate (B1/ thiamine) FAD (B2 riboflavin) NAD (B3 niacin) CoA (B5 panthothenate) Lipoic acid **a-Ketogluterate dehydrogenase
Pt with arsenic poisoning will have vomiting, rice water stools, and garlic breath due to inhibition of what?
Lipoic acid=> stops Pyruvate dh and thus TCA
ETC inhibitors: C1 CoQ (C3) CC/ C4 C5/ ATP synthase
C1= Rotenone C3= Antimycin Cc/C4= CO/ cyanide C5= Oligomycin
What are some ETC uncoupling agents/ increase O2 consumption and produce heat with NO ATP synthesis?
2,4-DNP
Aspirin
Thermogenin in Brown fat
What are the steps of Gluconeogenesis in: Mitochondria Cytosol Cytosol ER
Mito: Pyr—-biotin—> OAA
OAA—GTP—> PEP
F1,6-BP—–> F6P
ER: G6P—-> Gluc
Why can Odd chain FA be used for Glucose production but Even chains cannot?
Odd chains metabolized into Succinyl CoA which feeds into OAA and makes Glucose
Even chains only make Acetyl CoA
@ what sites are HMP shunt working the highest?
Sites of Steroid of FA synthesis Mammary glands Adrenal cortex Liver RBC
What is seen on the blood smear of person with G6PD def?
Heinze bodies= oxidized Hb
Bite cells= removal of heinze bodies
Why are Aldolase B and Uridyl transferase Def more severe than Fructokinase and Galactokinase def?
They deplete Phosphate levels by accumulation the phosphorylated forms of the sugars causing less for ATP production
Essential AAs:
Glucogenic
Ketogenic
Glucogeic== Met, Val, His Ketogenic= Leu, Lys
Acidic vs Basic AAs?
acidic= Asp, Glu basic= His, Arg, Lys
What two AAs are required in excess during growth?
Arg + His
What is the consequence of Hyperammonemia?
Depletion of a-ketogluterate leading to Inhibition of TCA cycle
What are some of the treatments for hyperammonemia?
Limit proteins
Phenylbuterate/ Benzoate= bind AAs
Lactulose
What cofactor is required for Phenylalanine hydroxylase and Tyrosine hydroxylase?
BH4 (tetrahydropterion)
- *Also required for Trp–> 5HT
- *Arg==> NO
The production of what NTs requires BH4?
Dopamine + 5HT
DOPA carboxylase converts DOPA-> DA but requires what cofactor?
B6 pyridoxine
Dopamine–> NE requires what cofactor?
Vitamin C
What kind of reaction makes NE–> Epi?
Methylation thus requires SAM
Histamin production requires what cofactor?
B6 (carboxylated from histidine)
Porphyrin production is made by what AA and requires what cofactor?
(Glycine + B6) + Succinyl CoA=> HEME
What things are derived from Arg?
NO
Creatine
Urea
What are some treatment options for Homocystinuria?
Dec Methionine
Inc Cysteine
Inc B6 & B12 & Folate
Urine Cyanide-Nitroprusside test is diagnostic of what genetic disease?
Cystinuria
Pt with mental retardation and increased serum alpha ketoacids has what defect?
Maple syrup urine disease=> blocked degradation of Branched amino acids
(Ile, Leu, Val)
Accumulation of Ceremide trihexoside leads to what?
Fabry's ==> a-galactosidase def CV + RENAL disease Angiokeratomas peripheral neuropathy *ONLY XR
Accumulation of Glucocerebroside leads to what?
Gauchers = Glucocerebrosidase def
Bone necrosis
Hepatosplenomegaly
Wrinkled Kupffer cells
Accumulation of Sphingomyelin leads to what?
Neiman Picks = Sphingomeyelinase def
Neurodegeneration
Cherry red Macula spots
HEPATOMEGALY
Accumulation of GM2 ganglioside leads to what?
Tay Sachs = Hexominidase def
Neurodegeneration
Cherry Red macula spots
NO hepatosplenomegaly
Accumulation of Galactocerebroside leads to what?
Krabbe = Galactocerebrosidase def
Neuropathy
Optic atrophy
Globoid cells
Accumulation of Cerebroside sulfate leads to what?
Metachromatic leukodystrophy = Arylsulfatase
Ataxia
Demyelination
Dementia
Accumulation of LCFA leads to what?
Adrenoleukodystrophy
Accumulation of Heparan/ dermatan sulfate leads to what?
Hurlers = Iduronidase def
*Gargoylism, Corneal clouding, Hepatosplenomegaly
Hunters = Iduronate sulfatase def
*Aggressive, NO corneal clouding
What are two metabolic defects in FA oxidation?
Carnitine def
Acyl-CoA dh def
Pt with weakness, hypotonia, Hypoketotic and hypoglycemic has what def?
Carnitine def
Pt with Hypoglycemia, Hypoketonemia, and increased Dicarboxylic acids has what def?
Acyl-CoA dh def
HMG-CoA is converted into what during Cholesterol synthesis?
Mevalonate by HMG-CoA reductase
Where is LPL located?
Endothelial cells
What is the action of Hormone sensitive lipase?
degradation of TG stores in adipose tissue
What apolipoprotein mediates Remnant uptake?
Apo E
**Only LDL does have them
What apolipoprotein activates LCAT?
apo A1
*ONly HDL
What apolipoprotein is a cofactor/ activator of LPL?
apo CII –> HDL gives to VLDL/ chylomicrons
What is the difference btwn Apo B48 & B100?
B100 in VLDL can BIND LDL receptors
