- these three metabolites provide parts of the 5-membered ring in the Purine

Formate, Glycine, Glutamine

- metabolites that provide parts of the 6-membered ring of Purine

CO2, Aspartate, Formate, Glutamine, Glycine

- committed step of Purine synthesis

- involves the transfer of an NH2 onto PRPP

- requires PRPP (Pentose Phosphate) and Glutamine

PRPP activation

- requires glycine, ATP and the 5-phosphoribosylamine and adds the glycine to what group

NH2

- group that is added by N10-Formyl-THF to the NH group from glycine

formyl (CHO)

- metabolites needed to make THF from folate or folic acid

DHFR (reductase) and NADPH

- cannot take up folate from the environment and must synthesize it

- the target of sulfa drugs

Bacterium

- causes arresting at S phase of the cell cycle

- megaloblastic anemia

- lack of Vitamin B12 could lead to this

- can be found in pregnant woman --> birth defects

- causes hyperhomocysteinemia (elderly)

- causes nueral tube defects

- Pernicious Anemia

- risk factor for colon cancer

Folate Deficiency

- required to rejuvenate the levels of methionine and folate

Vitamin B12

Is the nitrogen from glutamine transfered to the 1st carbon from glycine before or after ring closure in purine synthesis?

Before

What happens to the P-ribose complex after the nitrogen from glutamine is added and dehydration has occured?

Ring closure

- product of adding CO2, N from aspartate, and a formyl group from THF to the ring'd P-ribose complex and then dehydrating it make a second ring

IMP (inosine 5'-monophosphate)

Folate

- produced by amination of an IMP (utilizing aspartate)

adenosine 5'-monophosphate (AMP)

- produced by oxidating the C2 of IMP and then aminating it with glutamine

Guanosine 5'-monophosphate (GMP)

- facilitates the conversion of RNA nucleotides to DNA nucleotides

Ribonucleotide Reductase

- catalyzes the methylation of dUMP to TMP

Thymidylate synthase

- negatively regulates thymidylate synthase

Fluorouracil (5-FU)

- catalyzes the salvage synthesis of GMP

HGPRT

- causes self-mutilation of fingers

- caused by the absence of HGPRT

Lesch-Nyhan syndrome

- lack of what enzyme causes SCID (severe combined immunodeficiency or "bubble boy" disease)

adenosine deaminase (ADA)

- caused by an imbalance of purine synthesis and degradation from either increased synthesis or decreased HGPRT activity

- can lead to Gout, Lesch-Nyhan

Hyperuricemia

- deficiency can cause acute renal failure (kidney stones)

- increased pH of urine (more fluid intake) does NOT help

- breaks down ATP bound to ribose backbone

Adenine phosphoribosyl transferase (APRT

- deficiency can cause autism, psychomotor defects, hypotonia and seizures

- utilized in two steps of purine synthesis

Adenylosuccinate lyase deficiency

- inhibits dihydrofolate reductase (in the pathway to create the 1 carbon pool)

Aminopterin and methitrexate

(amethopterin)