Chapter 32 Flashcards
Nucleic Acids Acting as Precursors
Nucleic acids = precursors of numerous biochemicals in addition to proteins
Nucleic acids are precursors to immune system signals, hormones, membrane lipid constituents, electron carriers, and nucleotide bases
nucleic acids = information keepers of the cells; store and transfer information
- Nucleic acids are polymers of nucleotides
- Contain instructions for all cellular functions and interactions
- Like proteins, nucleic acids are linear molecules
- Constructed from four building blocks called nucleotides – made up of a 5 carbon sugar (either deoxyribose or ribose), attached to a heterocyclic ring structured (base), have at least one phosphoryl group
Name the two classes/pathways for the biosynthesis of nucleotides
DE NOVO PATHWAY = nucleotide bases are assembled from simpler compounds
=> the base itself is synthesized from simpler starting materials (ex. amino acids)
SALVAGE PATHWAYS = preformed bases are recovered and attached to an activated ribose units
=> a base is attached to a ribose, activated in the form of 5-phosphoribosyl-1-pyrophosphate (PRPP)
Nucleoside
a base (purine or pyrimidine) attached to a sugar (ribose sugar, PPP)
Nucleotide
a nucleoside w/ one or more phosphoryl groups (mono, di, tri)
Ribose
- the 5-C sugar in RNA
- hydroxyl group on carbon 2
Deoxyribose
- the 5-C sugar in DNA
- H-atom at carbon 2
DNA
constructed from four deoxyribonucleotides, differing from one another only in the ring structure of the bases – adenine (A), cytosine (C), guanine (G), thymine (T)
- Information content of DNA = sequence of nucleotides linked together by phosphodiester linkages
- DNA exist as a double-stranded helix, where the bases interact w/ each other - A w/ T, C w/ G
RNA
single-stranded form of nucleic acid
- Some regions of DNA are copied as a special class of RNA molecules called messenger RNA (mRNA) – a template for the synthesis of proteins (mRNA is frequently broken down after use, unlike DNA)
- RNA has similar composition to DNA expect, (1) base thymine (T) is replaced w/ uracil (U), (2) sugar component of the ribonucleotides contains an additional hydroxyl (-OH) group
Nomenclature of bases, nucleosides, and nucleotides for RNA
base. ribonucleoside. ribonucleotide
adenine. adenosine. adenylate
guanine. guanosine. guanylate
uracil. uridine. uridylate
cytosine. cytidine. cytidylate
Nomenclature of bases, nucleosides, and nucleotides for DNA
base. deoxyribonucleoside. deoxyribonucleotide
adenine. deoxyadenosine. deoxyadenylate
guanine. deoxyguanosine. deoxyguanylate
thymine. thymidine. Thymidylate
cytosine. deoxycytidine. deoxycytidylate
Pyrimidine Synthesis
Pyrimidines are synthesized from bicarbonate, aspartate, and ammonia, w/ glutamine serving as the nitrogen donor
The pyrimidine ring is synthesized first and subsequently attached to an activated ribose
The first step in pyrimidine synthesis is a 3-step reaction to form carbamoyl phosphate catalyzed by carbamoyl phosphate synthetase II (CPS II)
End product is one of the main RNA nucleotides (UMP) ~ uracil + ribose + phosphate
De novo synthesis of pyrimidine:
- carbamoyl phosphate production is the first step, catalyzed by carbamoyl phosphate synthetase II or CPS-II
- carbamoyl phosphate reactions w/ aspartate to form carbamoylaspartate by aspartate transcarbamoylase = key regulatory enzyme
- carbamoylaspartate cyclizes and oxidizes to form orotate
- orotate reacts w/ 5-phosphoribosyl-1 pyrophosphate (PRPP) to form orotidylate
- PRPP is synthesized from ribose 5-phosphate and ATP by PRPP synthetase
- Oritidylate is then decarboxylated to form uridine monophosphate (UMP or uridylate)
- UMP is then converted into UDP and UTP animation forms by triphosphate kinases and diphosphate kinases
- UDP is then converted to UMP in an amination reaction
CTP: UMP => UDP => UTP => CTP
Purine Synthesis
Purines are synthesized on a ribose molecule in the de novo pathways (starts w/ ribose sugar and then build the base)
This requires PRPP
PRPP combines w/ glutamine which is converted into 5-phosphoribosyl-1-amine, an initial commitment step
Reaction is catalyzed by glutamine phosphoribosyl amidotransferase (commitment step)
Nine steps are required to form inosine monophosphate (IMP or inosinate) from 5-phosphoribosyl-1-amine)
IMP is converted into adenylate (AMP) in a pathway that required GTP
IMPR is also metabolized to guanosine monophosphate (GMP or guanylate) in a pathway that requires ATP
Steps of purine synthesis
- Glycine is coupled to the amino group of phosphoribosylamine
- N10-Formyltetrahydrofolate (THF) transfer a formyl group to the amino group of the glycine residue to form formylglycinamide ribonucleotide
- The inner amide group is phosphorylated and then converted into an amidine by the addition of ammonia derived from glutamine
- An intramolecular coupling reaction form a five-membraned imidazole ring
- Bicarbonate adds first CO2 to the exocyclic amino group and then to a carbon atom of the imidazole ring
- The imidazole carboxylate is phosphorylated, and the phosphoryl group is displaced by the amino group aspartate
- Fumarate leaves
- Addition of a second formyl group from N-formyltetrahydrofolate (THF) occurs
- Cyclization completes the synthesis of inosinate, a purine nucleotide
Purine Modifications of IMP to AMP & GMP
AMP ~ formed by the addition of aspartate followed by the release of fumarate
GMP ~ formed from hydration/oxidation to from XMP
ATP and GTP are generated via additional phosphates
- Specific nucleoside monophosphate kinases and nonspecific diphosphate kinases
