day 1 Flashcards
(11 cards)
What are the main metabolic functions of nucleotides
Nucleotides serve many important roles in metabolism including
1. acting as energy carriers like ATP for muscle contraction and ion transport
2. serving as building blocks of RNA and DNA functioning as signaling molecules such as adenosine ADP cAMP and cGMP
3. acting as precursors for biosynthetic processes like mRNA capping and amino acid hydroxylation
4. forming parts of coenzymes like NAD FAD FMN and coenzyme A
5. acting as activated intermediates like UDP-glucose CDP-choline SAM and PAPS
6. serving as allosteric effectors such as ATP
7. inhibiting phosphofructokinase AMP, activating phosphorylase b and dATP, inhibiting ribonucleotide reductase
How does the concentration and distribution of nucleotides vary across cell types and conditions
ATP is the most abundant 5-prime nucleotide in most cells but the distribution varies by tissue type with red blood cells having high adenine nucleotides and liver containing a full range including NAD NADH UDP-glucose and UDP-glucuronic acid under normal conditions nucleoside triphosphates are dominant but in hypoxic states mono and diphosphates increase ribonucleotides are present in much higher concentrations than deoxyribonucleotides except during DNA replication when dNTPs rise total nucleotide pools such as ATP ADP and AMP stay constant though individual ratios shift to reflect the energy state the same applies to NAD and NADH levels
Why do nucleotide concentrations remain stable despite cellular changes and how is this achieved
The total concentrations of nucleotide pools like ATP ADP and AMP or NAD and NADH remain stable because of strict regulation by de novo synthesis and salvage pathways even when energy levels or redox conditions shift and individual nucleotide levels change the total amount remains fixed for metabolic stability for example if NADH increases NAD decreases proportionally to maintain a constant total pool
What degradation products of nucleotides are found in cells and where do they come from
Degradation products found in the cytosol include free nucleobases nucleosides 2-prime and 3-prime monophosphates and chemically modified bases and these come from the breakdown of endogenous nucleotides or nucleic acids as well as from external sources reflecting the ongoing turnover and recycling of nucleotide material within the cell
What is the reaction catalyzed by ribose-phosphate diphosphokinase and its main characteristics
Ribose-phosphate diphosphokinase also called PRPP synthetase catalyzes the reaction where ribose-5-phosphate reacts with ATP to form PRPP and AMP This enzyme requires one ATP per reaction which is converted to AMP not ADP and needs a divalent cation cofactor such as magnesium or manganese The enzyme transfers a pyrophosphate group to the 1-prime carbon of ribose-5-phosphate The reaction occurs in the cytoplasm It is activated by inorganic phosphate and inhibited by ADP and GDP as part of feedback inhibition by purine nucleotides
How is PRPP produced and what is its role in nucleotide metabolism
PRPP or 5-phosphoribosyl-1-pyrophosphate is produced from ribose-5-phosphate generated by the pentose phosphate pathway or from phosphorolysis of nucleosides PRPP is required for both de novo synthesis and salvage pathways of nucleotides Its production is catalyzed by PRPP synthetase and is tightly regulated because PRPP levels control multiple nucleotide synthesis pathways
What are the key regulatory properties of PRPP synthetase
PRPP synthetase requires ribose supplied by glucose-6-phosphate via the pentose phosphate pathway It absolutely requires inorganic phosphate and shows a sigmoidal velocity versus phosphate concentration curve The enzyme is inhibited by nucleotides such as ADP which is a competitive inhibitor of ATP and by 2 3-bisphosphoglycerate which competitively inhibits ribose-5-phosphate This tight regulation controls PRPP production and nucleotide synthesis
Which important reactions and pathways require PRPP
PRPP is essential for several important biosynthetic pathways These include the de novo synthesis of purine nucleotides salvage of purine bases where PRPP reacts with glutamine hypoxanthine guanine and adenine to form intermediates and nucleotides de novo synthesis of pyrimidine nucleotides salvage of pyrimidine bases and NAD synthesis where PRPP reacts with orotate uracil nicotinate nicotinamide and quinolate to form respective nucleotide derivatives
What clinical conditions are associated with PRPP synthetase abnormalities
Loss of function mutations in PRPP synthetase (PRS1) can cause severe clinical disorders as documented in some families On the other hand elevated PRPP levels can contribute to gout by increasing purine synthesis and uric acid production Thus balanced PRPP synthesis is critical for normal metabolism and disease prevention
What role does glutamine play in nucleotide synthesis
Glutamine is a critical amino acid substrate involved in five specific reactions of de novo nucleotide synthesis Although not essential glutamine availability strongly influences nucleotide synthesis rates especially during cell replication limiting glutamine can impair RNA and DNA production affecting cell division and growth
How is the overall de novo synthesis of purine and pyrimidine nucleotides regulated
The de novo synthesis pathways of purine and pyrimidine nucleotides are highly regulated at key enzymes PRPP amidotransferase controls purine synthesis while carbamoyl phosphate synthetase II regulates pyrimidine synthesis Regulation of these enzymes including PRPP synthetase ensures the proper balance of nucleotide pools for cell function and proliferation including maintaining correct ratios of UTP to CTP in cells
