Test 15 BC Flashcards
What contributes to the compact nature of heterochromatin and its transcriptionally INACTIVE state?
HEAVILY methylated DNA
Tight association with NON-acetylated histones
A 17 y/o F is being evaluated for short stature and primary amenorrhea.
Turner Syndrome= only 1 X chromosome (45, XO)
Chromosomes in her epithelial cells likely have heavily methylated DNA.
What happens to one X chromosome in normal females?
Normal 46, XX females, one X is deactivated by lyonization to form condensed heterochromatin. This is called a Barr body and is found at hte periphery of hte nucleus.
Methylation Makes DNA MUTE
How is mosaicism of the X chromosome accomplished in females?
DNA methylation–cystine residues are converted to methylcystine
What causes hypoxia induced lactic acidosis?
Low activity of pyruvate dehydrogeanse (oxidative phosphorylation pathway) and a high activity of lactate dehydrogeanse
What converts PEP to pyruvate?
Pyruvate Kinase (last step in glycolysis)
What bidirectional enzyme interconverts pyruvate and lactate?
Lactate Dehydrogenase
*Pyruvate to lactate in anaerobic conditions (skeletal muscle)
What role does lactate DH play in the liver?
Lactate generated from working skeletal muscle is taken up from the blood and converted to pyruvate for gluconeogenesis
What enzyme converts pyruvae to oxaloacetate?
Pyruvate carboxylase
What converts 2 phosphoglycerate to PEP?
enolase
What is the primary method of metabolizing dietary fructose in patients w/ essential fructosuria that is not present in normal individuals?
Fructose is metabolized to fructose -6- P
What are substrates for aldolase B?
F1P (fruct metabolism)
F1,6BP (glycolysis)
What enzyme converts glucose to sorbitol?
Aldose reductase
What causes sxs in pyruvate DH def?
PDH def PREVENTS the conversion of pyruvate to acetyl CoA so it is instead shunted to lactic acid and alanine> lactic acidosis and increased serum alaninein these patients.
Can range from neonatal death to mild episodic sxs in adults.
How do you tx pts with PDH def?
Lysine and Leucine are the onLy pureLy ketogenic AA
Increase intake of ketogenic nutrients
All steroid producing cells (adrenals, gonad, liver) must have a well developed…
SMOOTH ER
Contains enzymes for steroid and phospholipid biosynthesis
What is the site of synthesis of secretory proteins and N-linked oligosaccharide addition to many proteins?
RER
Mucous secreting goblet cells
Ab secreting Plasma cells
Both RICH in RER
Why is ornithine transport into the mitochondria essential for urea formation?
Ornithine is needed to combine with carbamoyl phosphate in the mitochondria to form citruline in the urea cycle.
What happens if there is a defect in the urea cycle?
Defects in the urea cycle lead to the accumulation of ammonia> neurological damage
How do you treat urea cycle defects?
protein restriction> less AA catabolism > less ammonia production
Mneumonic for remembering urea cycle?
Ordinarily (ornithine) Careless (carbamoyl phosphate) Campers (Citruline) Are (Aspartate) Also (Argininosuccinate) Frivolous (Fumurate) About (Argnine) Urination (Urea)
An infant presents w/ loss of motor skills, hepatosplenomegaly and a cherry rod spot on the macula.
Niemann Pick Disease
Death before age 3
Sphingomyelinase enzyme def> accumulation of sphingomyelin in phagocytes
…foamy histocytes in liver, spleen, skin (SOAP)
Niemann Pick disease
Gradual deposition of sphingomyelin in CNS also causes neuo degeneration> loss of previous acquired motor abilities
Def in Hexosaminidase A> G2 ganglioside accumulation
Tay Sachs
Deficiency in alpha-L-iduronidase>
heparan sulfate and dermatan sulfate accumulation
Hurler Syndrome
GARGOYLISM, corneal clouding
Def of glucocerebrosidase>
glucocerebroside accumulation
Gaucher
Def of alpha galactosidase> ceramide trihexoside accumulation
Fabry
Peripheral neuropathy, angiokeratomas, cardio/renal disease
Fabru
Def of HGPRT
Lesch-Nyhan syndrome (uric acid metabolism)
What can niacin be synthesized from?
tryptophan (synth requires B6 and B2)
What vit def leads to dermatitis, diarrhea, dementia?
Niacin = Pellagra
What is a precursor/constitutent of NAD+/NADP+?
Niacin
What vitamin is used to treat dyslipidemia?
B3= Niacin
Lowers VLDL
Increases HDL
What does a P50 shift from 26 to 20 mm Hg indicate?
The affinity of Hb for O2 is increased (LEFT shift, LUNGS)
How would a high-oxygen-affinity Hbs affect delivery of O2 to peripheral tissues?
Reduced ability to release O2 in peripheral tissues> renal hypoxia, increased EPO synthesis, compensatory erythrocytosis (increased RBC)> helps maintain normal O2 delivery> pts are asymptomatic
What causes hypoxia induced hemolysis?
Sickle cell disease
Deoxygenated HbS>
polymerizes>
excessive RBC sickling>
irreversible cell membrane damage
(shifts O2 curve RIGHT)
Hemolysis after taking antimalarials, sulfonamides, or ingestion of fava beans.
G6PD def
What is the regulatory substance that stimulates KATP channel closure in insulin producing beta cells?
ATP
What is the MC cause of AR xeroderma pigmentosum?
UV specific endonuclease def
A 6 y/o caucasian male presents w/ recurrent skin lesions on his face and upper extremties that rapidly progress to cancer.
Xeroderma pigmentosum
What enzymes are non-functional in xeroderma pigmentosum?
UV-specific endonucleases that prevent repair of pyrimidine dimers after UV light exposure
Specific endonucleases release oligonucleotides containing damaged bases> DNA Pol and ligase fill land reseal the gap in G1.
Nucleotide Excision repair
What happens in the skin after UV damage?
Pyrimidine dimers are formed in cell DNA>
recognized by specific endonuclease>
initiates repair by nicking strand at thymine dimer>
signals removal and replacement of damaged DNA.
Mutation three bases upstream from the AUG start codon is associated with what disease?
thalassemia intermedia
What is the Kozak sequence?
Initiates translation (mRNA binding to ribosomes);. Consists of a sequence defined by RccQUG (R is adenine or guanine)
What is thalessemia intermedia?
A form of beta thalassemia that is less clinically severe.
Hypochromic, microcytic thalessemia
What plays an important role in mRNA quality control in the cytoplasm?
P bodies
contain exonucleases, decapping enzymes and micro RNAs and play an important role in mRNA translation regulation and mRNA degradation
**RNA storage
Capping 5’ end, polyadenylation of 3’ end and splicing out of introns all occurs where…
Nucleus following trxn
