Flashcards in Chapter 32: Nucleotide Metabolism Deck (56)
1. Nucleotides make up
nucleic acids (DNA/RNA)
How do we get nucleotides?
They are nonessential nutrients - can be synthesized in the body.
Process of getting nucleoproteins in food.
1. digested in stomach by gastric acid and pepsin to protein and nucleotides
2. further broken down in small intestine by endonucleases to nucleotides
3. absorbed/degraded by nucleotidases to base, pentose, phosphate
4. base degraded/reused, pentose reused
Two types of bases and the difference between them
Purines and Pyrimidines:
Purines (A, G) have 2 rings
Pyrimidines (C, T, U) have 1
Structure of adenine
I don't know how to add pictures!
Structure of guanine
TO BE ADDED
Structure of cytosine
TO BE ADDED
Structure of uracil
TO BE ADDED
Structure of thymine
TO BE ADDED
What is the difference between ribose and deoxyribose?
Ribose- found in RNA, has OH group on carbon 2
Deoxyribose- found in DNA, has H group on carbon 2
What makes up a nucleotide?
Sugar, base, and phosphate
(vs nucleoside made up of base and sugar)
What is PRPP and how is it made?
An activate ribose made from ribose-5-phosphate. Enzyme PRPP synthetase makes it.
AKA 5-phosphoribosyl-1-pyrophosphate. (phosphate at position 5, pyrophosphate at position 1)
Where does ribose-5-phosphate come from?
the pentose phosphate pathway OR from ribulose with the enzyme ribokinase
What are the two synthesis pathways for nucleotides?
1. de novo (from bits and parts)- more energy, longer
2. salvage (recycle from pre-existing nucleotides)
De novo pyrimidine synthesis overview
pyrimidine ring synthesized from bicarbonate, aspartate, glutamine
1. bicarbonate + NH4 from glutamine -> carbamoyl phosphate= 2 ATP, carbamoyl phosphate synthetase II
2. carbamoyl phosphate + aspartate -> pyrimidine ring
3. pyrimidine ring activation w/ PRPP
De novo pyrimidine synthesis specifics- making carbamoyl phosphate
1. bicarbonate + ATP -> carboxyphosphate
2. carboxyphosphate + NH3 from Gln -> carbamic acid
3. carbamic acid + ATP -> carbamoyl phosphate
De novo pyrimidine synthesis specifics- attachment to ribose sugar (through orotate)
1. carbomoyl phosphate + aspartate -> carbamoylaspartate (enzyme= aspartate transcarbamoylase)
2. carbomoylaspartate + H -> Dihydroorotate (ring)
3. dihydroorotate + NAD+ -> orotate
De novo pyrimidine synthesis specifics- attachment to ribose sugar (orotate to UMP)
4. orotate + PRPP -> oretidylate
5. oretidylate + H -> uridylate (enzyme= orotidylate decarboxylase)
6. uridylate -> UMP
De novo pyrimidine synthesis specifics- attachment to ribose sugar (UMP to end)
7. UMP -> UDP (UMP kinase, ATP used)
8. UDP -> UTP (nucleoside diphosphate kinases)
9. UTP -> CTP (replace carbonyl group w/ amino group from glutamine, ATP used)
Conversion of UMP into other pyrimidines
Change UMP to dUMP, then change dUMP to dTMP through methylation using thymidylate synthase
De novo pyrimidine biosynthesis regulated by ____.
feedback inhibition- lots of UTP will prevent committed step (bicarbonate + NH4)
What is orotic aciduria?
Disease associated with defect in pyrimidine synthesis- it is hereditary, on chromosome III (UMP deficiency)
Causes loss of functional UMP synthetase.
Effects: no UMP, excess orotate, severe anemia, growth retardation
Treatment: feeding w/ UMP (changed to UTP which stops pathway by feedback inhibition)
Pyrimidine nucleotide degradation
Pyrimidine rings can be fully degraded to soluble structures (vs purines which make uric acid)
What are the sources of carbons and nitrogens in purine rings?
Aspartate gives 1 N; Glycine gives 1 N and 2 C; Glutamine gives 1 N; CO2 gives 1 C; N10-formyl-THF gives 2 C
What molecule donates the ribose onto which purine nucleotides are assembled?
How are the key steps in purine nucleotide biosynthesis regulated?
How are AMP and GMP made from IMP?
IMP -> XMP with IMP dehydrogenase, XMP -> GMP with GMP synthetase (also needs ATP)
IMP -> adenylosuccinate with Adenylosuccinate synthetase (needs GTP), adenylosuccinate -> AMP with adenylosuccinate lyase
Why is the salvage pathway for purine nucleotides important?
Useful b/c of high energy cost for de-novo synthesis of nitrogen bases
Important in some organs that lack enzymes required for de-novo synthesis pathway so they depend on exogenous source of purines
-ex: brain has low level of PRPP glutamyl amidotransferase
-erythrocytes/leukocytes can't synthesize 5-phosphoribosylamine
What enzymes add PRPP to bases to form nucleotides?