Biochemistry Flashcards
Essential fructosuria (AR, asymptomatic) is caused by deficiency in what enzyme?
Fructokinase deficiency
Why is essential fructosuria asymptomatic?
Some dietary fructose is converted by hexokinase to F6P –> into glycolysis
An activating mutation in PRPP can cause ___ (+ why?)
An activating mutation in PRPP can cause gout.
Because it results in an increased production and degradation of purines. Increased purine metabolism can cause hyperuricemia
What is aldolase B deficiency? How is it treated?
Aldolase B deficiency = Hereditary fructose intolerance; an enzyme required for the breakdown of F1P into DHAP and glyceraldehyde (which then enter into the glycolytic pw).
W/O Aldolase B –> buildup of toxic F1P –> hypolgycemia and vomiting after fructose ingestion (also FTT, jaundice, hepatomegaly)
Tx: strict dietary abstinence of fructose/sucrose
What are the 5’ and 3’ splice site sequences?
5' = GU 3' = AG
What is the most abundant amino acid in collagen?
Glycine (occupies every third AA position; this pattern + its small size allows collagen to form into its triple helical structure )
What does lactate dehydrogenase accomplish in anaerobic glycolysis?
(what happens when someone has a lactate dehydrogenase deficiency?)
Lactate dehydrogenase converts pyruvate to lactate, regenerating NAD+ from NADH
In LDH deficiency, muscle cells cannot regenerate NAD+ –> glycolysis is inhibited –> intense physical activity causes pain, fatigue, and muscle breakdown
What happens to pyruvate when there is oxygen?
What happens to pyruvate without oxygen?
Oxygen: Pyruvate converted to acetyl-CoA via pyruvate dehydrogenase
No Oxygen: Pyruvate converted to lactate via lactate dehydrogenase (can –> lactic acidosis)
Deficiency in _____ limits DNA synthesis and promotes megaloblastosis/erythroid precursor cell apoptosis
Can be reduced by ____ supplementation
Folate
- Without folate you cannot synthesize dTMP.
Thymidine
- Supplementation moderately increases dTMP levels
How does Ascorbic Acid (Vit C) play a role in collagen synthesis?
Ascorbic acid is a cofactor in the hydroxylation of proline and lysine residues, which is necessary for the formation of the collagen triple helix
What is the most common urea cycle disorder?
Ornithine Transcarbamylase (OTC) Deficiency
Patients will have hyperammonemia, elevated urinary orotic acid
What substrate serves as the allosteric activator of gluconeogenesis?
Acetyl-CoA
When AcCoA is abundant, it activates gluconeogenesis by increasing the activity of pyruvate carboxylase
Most common cause of galactosemia?
Galactose-1-phosphate uridyl transferase deficiency
Clinical: vomiting, lethargy, FTT soon after breastfeeding initiated
Alkaptonuria
- What is deficient
- What metabolism is blocked
Deficiency in homogentisic acid dioxygenase blocks the metabolism of tyrosine to fumarate
Buildup of homogentisic acid –> black urine exposed to air, blue black pigmentation on face, ochronotic arthropathy
Which vitamin is necessary for AA transamination and decarboxylation as well as gluconeogenesis?
Vitamin B6 (Pyridoxine)
What makes elastin “rubber-like”?
Extensive lysine cross-linking between elastin fibers, facilitated by lysyl oxidase
Hyperammonemia (in hepatic encephalopathy) results in depletion of which 2 metabolites
1) alpha-ketoglutarate –> inhibition of krebs cycle
2) Glutamate (excitatory NT) –> accumulation of glutamine –> astrocyte swelling and dysfunction
Cardiomegaly, macroglossia, and profound muscular hypotonia in early infancy
Acid maltase/alpha-glucosidase deficiency AKA Pompe Disease
Muscle biopsy: glycogen accumulation w/in lysosomal vesicles
How do you diagnose thiamine deficiency?
Baseline erythrocyte transketolase activity = low but increases after addition of thiamine pyrophosphate
What is the major AA responsible for transferring nitrogen to the liver for disposal?
Alanine
During protein catabolism, amino groups are transferred to alpha-ketoglutarate to form glutamate –> glutamate processed in the liver to form urea, which is the primary disposal form of nitrogen in humans
Which way does hypothermia shift the Hb-O2 dissociation curve?
Hypothermia shifts the curve left
Decreased temperatures help to stabilize bonds between O2 and Hb, this increasing Hb’s O2 affinity, shifting the dissociation curve left
other causes of left shift:
- increased pH
- decreased 2,3-DPG
What is the function of Primase?
Primase = DNA-dependent RNA polymerase that incorporates short RNA primers into replicating DNA
What enzyme is deficient in McArdle’s Disease?
Myophosphorylase
–> failure of muscle glycogenolysis –> decreased exercise tolerance, rhabdomyolysis
Neimann-Pick Disease
- Enzyme Deficiency
- Symptoms
AR deficiency in sphingomyelinase
Hepatosplenomegaly, hypotonia, neurologic degeneration, cherry red spot on macula
Two diseases prevalent in the Ashkenazi Jewish Population
+
What is the clinical difference between the two
Neimann-Pick disease = AR deficiency in sphingomyelinase
Tay-Sachs disease = AR deficiency in B-hexosaminidase A
They both involve neurologic regression and cherry-red spot on the macula
- NP with hepatosplenomegaly
- TS without hepatosplenomegaly
What makes up the spliceosome
Primary mRNA transcript \+ snRNPs (small nuclear ribonucleoproteins) \+ other proteins
What are the 3 major proteins that eliminate oxygen free radicals?
Superoxide Dismutase
Catalase
Glutathione Peroxidase
B12 deficiency results in buildup of what two metabolites?
- Methylmalonic acid (–> buildup disrupts myelin synthesis –> subacute combined degeneration)
- Homocysteine (–> impaired DNA synthesis)
What is the treatment for urea cycle defects?
Protein restriction to prevent the accumulation of ammonia
How can you ID mitochondria on EM?
Double membrane and wavy cristae
Tell me about mitochondrial DNA
- maternally derived
- small, circular, resembling prokaryotic DNA
- most common non-nuclear DNA found in eukaryotic cells
What enzyme is responsible for degrading bilirubin into biliverdin?
Heme oxygenase
What is the composition of fetal hemoglobin?
Alpha-2 Gamma-2
Carnitine Deficiency will result in deficient synthesis of what metabolite when glucose levels are low?
Acetoacetate/ketone bodies
FA cannot be transported into the mitochondria, so B oxidation of FA –> acetylCoA –> ketone bodies cannot be synthesized
_____ is rapidly metabolized because it bypasses phosphofructokinase, the major rate-limiting enzyme of glycolysis
Fructose
What two enzymes does lead inhibit (and what are the downstream effects as a result of this)?
Lead inhibits ferrocheletase and delta-aminolevulinic acid (ALA) dehydretase
Resulting in anemia, ALA accumulation, and elevated zinc protoporphyrin levels
(long term = neurotoxicity)
What sequence is found at the 3’ end of tRNA
CCA
Used as a recognition sequence by proteins (3’ terminal hydroxyl group of the CCA tail = AA binding site)
Three steps of PCR
- Denaturation
- Annealing (of premade DNA primers complementary to regions of DNA flanking segment of interest)
- Elongation
What is deficient in Lesch-Nyhan Syndrome?
HGPRT – defective purine salave pathway
- compensatory increase in PRPP amidotransferase acitivity
SX: (HGPRT) Hyperuricemia, Gout, Pissed off, Retardation, dysTonia
What is defective in Ataxia Telangiectasia?
DNA repair
As a result, DNA is hypersensitive to ionizing radiation
SX: cerebellar ataxia, oculocutaneous telangiectasias, repeated sinopulmonary infections, increased risk for malignancy.
What are the steps of the urea cycle?
Ordinarily, Careless Crappers Are Also Frivolous About Urination
Ornithine Citrulline Aspartate Arginosuccinate Fumarate Arginine Urea
What is the sequence of enzymatic activity in Nucleotide Base Excision Repair?
Glycosylase
Endonuclease (5’) + Lyase (3’)
Polymerase
Ligase
What is the function of DNA Polymerase I in bacterial DNA replication?
Removal of RNA primers via 5’ –> 3’ exonuclease activity
Replacing them with DNA (5’ –> 3’ polymerase activity)
Lactase deficiency can be…
Primary
or
Secondary – after inflammatory or infectious processes damage the SI microvilli
(ex = celiac, giardiasis)
Non-Polar Hydrophobic AA (make up transmembrane domains)
VIP GAL TRY METh or PHEn
Valine Isoleucine Proline
Glycine Alanine Leucine
Tryptophan
Methionine
Phenylalaline
What AA is important in acid secretion (via the creation of ammonium)?
Glutamine is metabolized to glutamate –> generate ammonium excreted in urine & bicarbonate absorbed into blood
responsible for a vast majority of renal acid excretion in chronic acidotic states
What is the role of the Ubiquitin Proteasome Pathway in the immune response?
To recognize and degrade foreign intracellular proteins –> enabling them to be coupled to MHC Class I in the ER
What catalyzes the rate limiting step in de novo fatty acid synthesis?
Cytosolic acetyl-CoA carboxylase (AcCoA –> malonyl-CoA)
malonyl CoA, in turn, inhibits the beta oxidation of FA
What is sorbitol metabolized to?
Sorbitol is metabolized to fructose by sorbitol dehydrogenase
*noteworthy that insufficient sorbitol dehydrogenase in the lens = why hyperglycemia causes blurry vision (sorbitol = osmotically active)
What do poisonous mushrooms (amatoxins) do?
Potent inhibitors of RNA Pol II –> stops mRNA synthesis
What happens in the smooth ER?
Smooth ER contains enzymes for steroid and phospholipid biosynthesis
Steroid-producing cells have a well-developed smooth ER
What enzyme (found in adipose tissue) drives the breakdown of stored triglycerides into FFA and glycerol? (active in times of starvation to provide substrates for hepatic gluconeogenesis and ketone body formation)
Hormone Sensitive Lipase
Dietary Energy (Cal per gram)
Protein = 4kcal/gram Carbohydrate = 4kcal/gram Fat = 9kcal/gram Ethanol = 7kcal/gram
