Biochem

Question 1

How are proteins targeted for lysosomes modified differently in the golgi apparatus than those destined for extracellular secretion?

Answer 1

• Golgi body phosphotransferase enzyme catalyzes the phosphorylation of mannose residues allowing for proper transit through Golgi apparatus
• Deficient phosphorylation of these residues seen in I-cell disease

Question 2

What takes over the role of fructokinase in fructokinase deficiency?

Answer 2

Hexokinase; converting fructose –> fructose-6-phosphate

Question 3

What is the primay defect is familial dysbetalipoproteinemia (type III hyperlipoproteinemia); clinical features of this disease?

Answer 3

• AR; lack of ApoE3 and ApoE4 –> decreased clearance of chylomicrons and VLDL remnants by the liver
• Eruptive and palmar xanthomas and premature atherosclerosis

Question 4

What is the function of the TATA and CAAT boxes found within the eukaryotic genome?

Answer 4

Promoters of transcription by serving as bindings sites for transcription factors and RNA polymerase II

Question 5

What is found at the 3’ end of tRNA and what is its function?

Answer 5

• A 3’ CCA tail used as a recognition sequence by proteins
• The 3’ terminal hydroxyl group of CCA tail serves as AA binding site

Question 6

Hereditary fructose intolerance is due to a deficiency of aldolase B which leads to a buildup of what; how does this cause toxicity?

Answer 6

Fructose-1-phosphate –> depletes intracellular phosphate and inhibits activation of hepatic phosphorylase and gluconeogenesis

Question 7

What are presenting sx’s of hereditary orotic aciduria?

Answer 7

• Physical and mental retardation i.e., low height/weight, etc.
• Megaloblastic anemia
• Elevated urinary orotic acid levels

Question 8

What is the primary function of the nucleolus?

Answer 8

• Synthesis and assembly of immature 60S and 40S ribosomal subunits
• Which are exported from the nucleus to fully mature in the cytoplasm

Question 9

The rubber-like properties of elastin are due to what?

Answer 9

High content of nonpolar (hydrophobic) AA’s and extensive cross-linking btw elastic monomers facilitated by lysyl oxidase

Question 10

What is the most common enzyme deficiency leading to impaired beta-oxidation; classic signs and sx’s include what?

Answer 10

• Medium chain acyl-CoA dehydrogenase
• Classic findings after a fast: hypoketotic hypoglycemia + mild hepatomegaly + liver dysfunction

Question 11

Which lysosomal storage disease is associated with hepatosplenomegaly, pancytopenia, and severe bone pain?

Answer 11

Gaucher disease –> beta-glucocerebrosidase deficiency

Question 12

Expression of which enzyme in the adrenal medulla is upregulated by cortisol and is responsible for converting NE –> epinephrine?

Answer 12

Phenylethanolamine-N-methyltransferase (PNMT)

Question 13

The alteration of the hepatic NAD/NADH ratio in alcoholics induces fatty liver through inhibition of which 2 pathways?

Answer 13

• Gluconeogenesis and Fatty acid oxidation
• Also assoc. w/ impaired lipoprotein assembly and increased peripheral fat catabolism

Question 14

What is responsible for the clinical variability of mitochondrial inherited diseases?

Answer 14

Heteroplasmy: during mitosis mitochondria are randomly distributed btw daughter cells; some cells contain damaged mtDNA and others are normal

Question 15

What is the wobble hypothesis?

Answer 15

• Certain tRNA molecules can recognize multiple different codons coding for the same amino acid
• Stats the first 2 nucleotide positions on the mRNA codon require traditional (Watson-Crick) base pairing, whereas the third “wobble” nucleotide position may undergo less stringent (nontraditional) base pairing
• i.e., 1 tRNA molecule recognizes 2 codons (CUC and CUU) because only the first 2 nucleotide positions form traditional bonds

Question 16

A child with severe intellectual disablility, history of seizures and abnormal pallor of catecholaminergic brain nuclei (substantia nigra, locus ceruleus, and vagal nucleus dorsalis) on autopsy is suggestive of what condition?

Answer 16

• Phenylketonuria
• Deficiency of phenylalanine hydroxylase (most common) or dihydropteridine reductase

Question 17

What is a key distinguishing feature seen in the hepatocytes of patient with Cori Disease (Type III)?

Answer 17

Cytosolic accumulation of glycogen with abnormally short outer chains = limit dextrans

Question 18

Hepatic steatosis is a cardinal manifestation of which glycgoen storarge disorder?

Answer 18

von Gierke disease –> glucose-6-phosphatase deficiency

Question 19

Branched chain alpha-ketoacid dehydrogenase requires which 5 co-enzymes? (hint: mnemonic)

Answer 19

• Thiamine
• Lipoate
• Coenzyme A
• FAD
• NAD

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Question 20

What is the most abundant amino acid in collagen?

Answer 20

• Glycine
• Triple helical conformation of collagen occurs due to the simple and repetitive AA sequence within each alpha chain, in which glycine (Gly) occupies every 3rd AA position (Gly-X-Y)

Question 21

Which labratory analysis method is used to measure the degree of methylation and determine the number of CGG repeats in Fragile X Syndrome?

Answer 21

Southern Blot

Question 22

A 3-year old boy experiences progressive development of spastic diplegia, abnormal movement, growth delay w/ labs showing elevated arginine levels in the plasma and CSF; what is the diagnosis?

Answer 22

• Arginase deficiency
• Arginase catalzyes the breakdown of arginine –> urea + ornithine during the urea cycle
• Unlike other urea cycle disorders these pt’s have mild or no hyperammonemia

Question 23

What is the major RNA product of RNA polymerase I, II, and III in eukaryotes?

Answer 23

• RNA polymerase I = Ribosomal RNA
• RNA polymerase II = Messenger RNA
• RNA polymerase III = Transfer RNA

Question 24

What is the MOA of the toxin, Ricin (from the castor oil plant Ricinus communis)?

Answer 24

Inhibits protein synthesis by cleaving rRNA component of eukaryotic 60S subunit

Question 25

Thiamine is a necessary co-factor for which enzymes?

Answer 25

• Pyruvate dehydrogenase
• α-ketoglutarate dehydrogenase
• Transketolase

Question 26

What is the hallmark of tx for Maple Syrup Urine Disease?

Answer 26

Dietary restriction of BCAA’s = Leucine, Valine, and Isoleucine

Question 27

Supplementation and restriction of what may help prevent adverse events in pt’s with homocystinuria due to deficiency of cystathione beta-synthase?

Answer 27

• High dose pyridoxine (B6) a cofactor for the deficient enzyme
• Restriction of methionine