Biochemistry

Question 1

Hereditary orotic aciduria (AR)- presents with failure to thrive and developmental delay (cant lift head or sit upright)- low in height and weight percentiles

Low hemoglobin, macrocytic (MCV 100+), reticulocytes low, and orotic acid crystals in the urine, ammonia is normal

Tx with uridine

Answer 1

HOA is a disorder if de novo pyridimine synthesis due to a defect in uriidine 5-monophosphate synthase (impaired conversion of orotic acid to UMP, resulting in high urine levels) that results in phsycial and mental retardation

Note that elevated orotic acid levels may also be seen in ornithine transcarbamlyase deficiency, howverm pts with this condition classically have failure to trhive and hyperammonemic encephalopathy within the first few weeks of life due to impaired urea synthesis

Question 2

The zinc-finger motif is the most common DNA-binding domain in the body. Zinc-finger motifs are composed of chains of AAs bound together around a zinc atom via linkages with cysteine (and somes histidine) residues

THis forms a stable, finger shaped structure containing 2 antiparallel B strands and an a-helix.

Answer 2

Although most hormones alter transcription regulation in some way, only intracellular receptors located in the cytoplasm or nucleus can act directly as transcription factors. Thes intracellular receptors typically bind lipid-soluble hormones because the ligand has to diffuse across the cell membrane to reach the receptor.

Once bound to their ligand, these receptors bind directly to target DNA sequences via zinc fingers to regulate gene expression. Examples include steroids (e.g. estrogen, aldosterone, cortisol), thyroid hormone, and fat-solbule vitamine receptors

Question 3

Non-lipid soluble hormones interact with transmembrane receptors found on the cell membrane. These recerpotrs use a signal tranduction cascade involving 2ndary messengers with subsequent activation of non-receptor-associated transcription factors; they dont conain DNA-binding domains

Ex include GPCRs that bind ACTH, ADH, epi, and glucagon

Question 4

Telomerase is a ribonucleoprotein that adds TTAGGG repeats to the 3’ end of chromosomes. Similar to other reverse transcriptases in that it synthesized single-stranded DNA using single-stranded RNA as a template (RNA-dependent DNA polymerase)

2 subunits- telomerase reverse transcriptase (TERT) and telomerase RNA component (TERC). TERC is a built-in RNA template that is repeatedly read by the TERT subunit to add TTAGGG DNA sequence repeats to telomerase

Answer 4

Stem cells have very long telomeres due to their high telomerase activity, allowing them to proliferate indefinitely in a controlled manner

In contrast, most terminally differentiated adult somatic cells (e.g. ycoardial cells, neurons, pancreatic B cells) have short telomeres as they do not express telomerase and their telomeres shortened

Note that syndromes of premature aging (e.g. Bloom syndrome) are associated with shortened telomeres