B&B Biochemistry Flashcards
Located in nucleus of eukaryotic cells
-Contains genetic code
DNA
Located in cytoplasm of prokaryotic cells
DNA
The DNA structure is composed of
Sugar (ribose) backbone, Nitrogenous base, phosphate
Made up of a pentose sugar, nitrogenous base, and phosphate group
Nucleotide
What if the difference between nucleotides and nucleosides?
Nucleotides have a phosphate group
Synthesized as monophosphates and then converted to triphosphate form
Nucleotides
Occurs in segments with GC patterns (GC Islands)
DNA methylation
Inactivates transcription
DNA Methylation
Unmethylated GC stimulates an
Immune Response
Bacteria methylate
Cytosine and adenine
Methylation protects bacteria from
Viruses (phages)
In bacteria, non-methylated DNA is destroyed by
Endonucleases
Found in nucleus of eukaryotic cells
-DNA plus proteins
Chromatin
Units of histones plus DNA
Nucleosome
Histones contain basic amino acids with high content of
Lysine and arginine
Positively charged and binds to the negatively charged phosphate backbone
Histones
Distinct from other Histones because it is not in the nucleosome core.
-Larger and more basic
H1
Fever, joint pains, and rash after starting a drug
Drug-induced lupus
Caused by anti-histone antibodies in 95% of cases
Drug-induced lupus
Classic lupus is caused by
anti-dsDNA
What are the three classic drugs that cause drug-induced Lupus?
Hydralazine, Procainamide, and Isoniazid
Condensed chromatin where DNA sequences are not transcribed
-Significant DNA methylation
Heterochromatin
Less condensed form of chromatin
-Transcriptively active
Euchromatin
In heterochromatin, we see significant
DNA methylation
In euchromatin, we see significant
Histone Acetylation
Acyl group is added to lysine, which relaxes the chromatin for transcription
Histone acetylation
We see increased expression of some histone deacetylases in some
Tumors
What are two things that histone deacetylase inhibitors are used for?
Anti-cancer and Huntington’s
A possible mechanism for Huntington’s disease is
Histone Deacetylation
cAMP levels mediate
Blood flow
cGMP often serves as a
Secondary messenger
RNA is synthesized first and then is later converted to
DNA
The goal of purine synthesis is to create
AMP and GMP
Step 1 of purine synthesis is to create
PRPP
Then, step 2 of purine synthesis is to create
IMP
What are the three nitrogen sources from purine synthesis?
Aspartate, Glycine, and Glutamate
What are the three carbon sources during purine synthesis?
CO2, Glycine, and Tetrahydrofolate
A major contributor to the formation of purines is
Folate
IMP is then used to create
AMP and GMP
Purine synthesis starts with ribose phosphate from the
HMP shunt
Converts ribonucleotides to deoxyribonucleotides
Ribonucleotide Reductase
Inhibits IMP dehydrogenase
-Blocks the conversion of IMP to GMP
Ribavirin
Ribavirin inhibits the synthesis of
Guanine nucleotides (purines)
An immunosuppressant that inhibits IMP dehydrogenase
Mycophenolate
Slavages the bases adenine guanine, and hypoxanthine
Purine Salvage
Purine salvage requires
PRPP
In the purine salvage pathway, hypoxanthine and guanine are converted to IMP and GMP respectively by
HGPRT
In the purine salvage pathway, adenine is converted to AMP by
APRT (Adenine phosphoribosyl transferase)
A chemotherapy agent that mimics hypoxanthine and guanine
6-Mercaptopurine
Added to PRPP by HGPRT to create Thioinosinic acid
6-Mercaptopurine
The overall effect of 6-Mercaptopurine is a decrease in
IMP, AMP, and GMP
An immunosuppressant that is converted to 6-MP
Azathioprine
In the purine breakdown pathway, hypoxanthine is converted to Xanthine by
Xanthine Oxidase
In the purine breakdown pathway, Guanine is converted to Xanthine by
Guanase
Then, Xanthine (from hypoxanthine and guanine) is converted to uric acid by
Xanthine oxidase
Crystal deposition in joints caused by excess uric acid
Gout
Can occur from high cell turnover (trauma or chemo) and consumption of purine-rich foods like meat and seafood
Gout
The treatment for gout is
Xanthine oxidase inhibitor (Allopurinol)
Azathioprine and 6-MP are metabolized by
Xanthine oxidase
May boost effects of 6-MP and increase toxicity of the drug
Co-treatment with allopurinol
X-linked absence of HGPRT
-results in excess uric acid production
Lesch-Nyhan Syndrome
In Lesch-Nyhan syndrome, we see excess denovo purine synthesis, which means increases in
PRPP and IMP
The classic presenting feature of Lesch-Nyhan Syndrome is
Self-mutilating behavior
A male child with motor symptoms, self mutilation, and gout, is the classic presentation of
Lesch-Nyhan Syndrome
The goal of pyrimidine synthesis is to create
CMP, UMP, and TMP
Step one of pyrimidine synthesis is to make
Carbamoyl phosphate
In step one of pyrimidine synthesis, it is important to note that
Ring is formed first, then ribose is added
Step 2 of pyrimidine synthesis is to make
Orotic Acid
Step 3 of pyrimidine synthesis is to make
UMP
Orotic acid and PRPP are combined to make UMP by
UMP synthase
The key point of pyrimidine synthesis is that UMP is synthesized first and the from UMP we derive
CMP and TMP
The pryimidine ring is made up of
2 Nitrogens and 4 Carbons
3 carbons and 1 nitrogen of the pyrimidine ring are derived from
Aspartate
1 nitrogen and 1 carbon of the pyrimidine ring are derived from
Carbamoyl Phosphate
Autosomal recessive disorder caused by a defect in UMP Synthase
Orotic Aciduria
Orotic aciduria is characterized by a loss of pyrimidines and a buildup or
Orotic Acid
What are 3 key findings of Orotic Aciduria?
- ) Orotic acid
- ) Megaloblastic Anemia
- ) No B12/Folate response
- ) Growth Retardation
How do we treat Orotic Aciduria and what is the effect of this treatment?
Treat with Uridine
-Bypasses UMP synthase
Key urea cycle enzyme, which functions to combine carbamoyl phosphate with ornithine
Ornithine TransCarbamoylase (OTC)
OTC combines carbamoyl phosphate w/ ornithine to make
Citrulline
OTC deficiency results in increased carbamoyl phosphate which causes increases in
Orotic Acid
We want to be careful not to confuse OTC deficiency with
Orotic aciduria
How do we distinguish between OTC deficiency and orotic aciduria?
OTC has increased ammonia levels