Carbon Pool Flashcards
_____ is the most oxidized one-carbon form that is transferred by biotin in carboxylation reactions
CO2
_______ is produced in cells via the reduction of dietary folate
tetrahydrofolate (FH4)
_______ is synthesized by bacteria and higher plants from the bicyclic pteridine ring, p-amino-benzoic acid (PABA) and glutamate
Folate
why don’t sulfa drugs affect human cells?
because they block the synthesis of PABA for folate synthesis, which human cells can’t do
Enzymes of brush border epithelium cleave how many of the glutamate residues before absorption?
all but one
what was the first class of drugs to be discovered that could treat bacterial infection
sulpha drugs
Folate is reduced to dihydrofolate and then to tetrahydrofolate by what enzyme and what else is needed??
dihydrofolate reductase and NADPH
what drug targets dihydrofolate as an anticancer agent?
methotrexate
B12 deficiency can cause what to occur?
the methyl folate trap, in which THF is converted into a resivoir that has no way of being metabolized, resulting in a folate deficiency
Tetrahydrofolate (FH4) obtains one carbon units from what 5 things as part of their catabolism?
serine, glycine, histidine, formaldehyde, and formate
These 1-carbon units that are attached to FH4 for their catabolism are ______ and ______
oxidized and reduced
once the 1-carbon units that are attched to FH4 for their catabolism are reduced they can/cannot be reoxidized
cannot
further reduction of the CH3 groups to methane (CH4) from serine, glycine, histidine, formaldehyde, and formate can be done by _____
intestinal bacteria, but not humane cells
what is the major source of 1-carbon groups carried by FH4?
serine
serine’s hydroxymethyl group is transferred to act as a 1-carbon group by a reversible reaction that uses pyridoxal phosphate and generates what?
generating N5,N10-methylene-FH4 and glycine
Since serine can be synthesized from ______, dietary _____ serves as a source of carbon for the 1-carbon pool
glucose,carbohydrate
the reversible reaction between glycine and serine is catalyzed by what enzyme?
serine hydroxymethyl transerase
dUMP acts as a 1-carbon recipient when catalyzed by what enzyme into what product?
catalyzed by thymidylate synthase into dTMP
how does methotrexate act as an anticancer agent?
it has essentially the same structure as FH4 (except methrotrexate has an additional amino group)so it prevents the conversion of FH2 (folate) to FH4 (tetrahydrofoloate)
explain how 5-FU (5-fluorouracil) blocks DNA replication and cell growth
since 5-FU is a pyrimidine analog, the cell inserts it into DNA where thymine should be, thus disrupting cell growth and DNA replication, this is especially import for tumor cell which have a greater rate of cell division than normal healthy cells
5-FU gets converted into cells to _____ which causes “_____death”
FdUMP, thymineless
what enzyme plays the role of catabolizing most naturally occurring pyrimidines (uracil and thymine) as well as 5-FU (the anticancer agent) into metabolically active forms?
dihydropyrimidine dehydrogenase (DPD)
dihydropyrimidine dehydrogenase (DPD) converts 5-FU from an inactive metabolite into an active one through an enzymatic process that is irreversible or reversible?
irreversible
__________inactivates uracil reductase (DPD), the enzyme that rapidly degrades 5-FU in cancer patients. Thereby improving the efficacy, the therapeutic index, and the oral bioavailability of 5-FU in laboratory animals.
Eniluracil (5-ethynyluracil)
The combination therapy, Cytefuran, combines what two drugs for the Tc of solid tumors?
5-FU and eniluracil
In the absence of B12, all of the folate is eventually trapped as the THF-CH3 (N5-methyl FH4), resulting in what conidition?
megaloblastic anemia
define megaloblastic anemia
is an anemia that results from inhibition of DNA synthesis during red blood cell production, can result from the absence of B12
Folate deficiencies in early pregnancy can result in defects such as _________
spina bifida
_______ is a developmental congenital disorder caused by the incomplete closing of the embryonic neural tube. This condition can be a result of ______ deficiencies early in pregnancy
spina bifida, folate
deficiencies of what two things can cause megaloblastic anemia?
folate and b12
Is FH4 required for cell division?
yes, because it is required for the synthesis of purine bases, which are needed for DNA replication
________ is an abnormal growth of tissue, and when also forming a mass is commonly referred to as a tumor
neoplasm
what is N-formiminoglutamate and it’s significance?
it is an intermediate in the metabolism of histidine, so it is used for 1-carbon donation to THF, resulting in N5-Formimino THF
what enzyme does methotrexate inhibit?
dihydrofolate reductase
5-FU is metabolized by what enzyme?
dihydropyrimidine dehydrogenase
what blocks the conversion of dUMP to dTMP?
5-FU
another name for Vit B12?
Cobalamin
