Biochemistry Flashcards
What enzyme does Leflunomide inhibit?
Inhibits dihydroorotate dehydrogenase in pyrimidine synthesis
What enzyme does methrotrexate (MTX), Trimetrhoprim (TMP), and Pyrimethamine inhibit
They inhibit dihydrofolate reductase (decreases deoxythymidine monophosphoate) in pyrimidine synthesis
- MTX in humans.
- TMP in bacteria
- Pyrimethamine in protozoa.
What does 5-fluorouracil (5-FU) and its product capecitabine form and what enzyme does that formation inhibit?
They form 5-F-dUMP which inhibits thymidylate synthase (which decreases dTMP) in pyrimidine syntesis
What does 6-mercaptopurine (6-MP) and its prodrug azathioprine inhibit?
They inhibit de novo purine synthesis
What enzyme does mycophenolate and ribavirin inhibit?
They inhibit inosine monophosphate dehydrogenase in purine synthesis
What enzyme does Hydroxyurea inhibit?
It inhibits ribonucleotide reductase in purine and pyrimidine synthesis
In what phase does histone and DNA syntesis occur?
Their synthesis occurs during S phase
What is the structural component of a nucleoside?
a nitrogenouse base + (deoxy)ribose (sugar)
What is a nucleotide?
A compound consisting of a nucleoside linked to a phosphate group. They form the basis structural unit of nucleic acids such as DNA.
Name the purines
Adenine & Guanine
- They consist of 2 rings
Name the pyrimidines
Thymine (has a methyl group), Cytosine, Uracil
- They consist of 1 ring
What is stronger a G-C bond or a A-T bond and why?
A G-C bond is stronger because it has three Hydrogen bonds unlike A-T bonds that only has 2 hydrogen bonds
What are the Amino Acids needed for Purine synthesis?
Glycine
Aspartate
Glutamine
What enzyme is required for adenosine and deoxyadenosine degradation and what happens when there is a deficiency in that enzyme?
- Adenosine deaminase (ADA) is required for their degradation.
- In ADA deficiency dexyadenosine triphosphate levels increase which causes lymphotoxicity.
- ADA deficiency is on of the major causes of autosomal recessive severe combined immunodeficiency disease (SCID)
What does hypoxanthine-guanine phosphoribosyltransferase (HGPRT) do?
It converts hypoxanthine to inosine monophospate (IMP) and guanine to guanosine monophosphate (GMP)
What happens when hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is absent?
- There is a defective purine salvage which results in excess uric acid production and de novo purine synthesis.
- It results in Lesch-Nyhan syndrome which is X-linked recessive.
What are the common clinical findings in Lesch-Nyhan Syndrome
- HRPRT*
- Hyperuricemia (orange “sand” [sodium urate crystals] in diaper)
- Gout
- Pissed off (agression, self mutilation)
- Retardation (intelectual disability)
- DisTonia
What is the treatment for Lesch-Nyhan Syndrome
Allopurinol or febuxostat (2nd line)
What enzyme does Allopurinol and febuxostat inhibit?
They inhibit xanthine oxidase
What are the genetic code features?
- Unambiguous: each codon specifies only 1 amino acid
- Degenerate / redundante: most amino acids are coded by multiple codons (exeptions: methionine (AUG) and tryptophan (UGG) encoded by only 1 codon.
- Commaless, nonoverlapping: Read from a fixed starting point as a continuous sequence of bases (exeptions: some viruses)
- Universal: Genetic code is conserved throughout evolution (exception in humans: mitochondria)