Nitrogen Metabolism Flashcards
What are Primary metabolites?
Needed for normal operation of metabolic pathways/ cellular function
What are Secondary metabolites?
organic compounds that help cells with growth and development but not needed for life.
ex. thyroid hormones, not needed but helps to thrive
what is the structure of pyruvate? What is it derived from?
h3C-C=O
l
O=C-O(-)
alanine
what is the structure of oxoacetate (OAA)? what is it derived from?
(-)O-C=O
l
CH2
l
C=O
l
O=C-O(-)
derived from Aspartate
what is the structure of alpha ketoglutarate? (alpha-KG)
O(-)-C=O
l
CH2
l
CH2
l
C=O
l
O=C-O(-)
glutamate
How are the keto acids pyruvate, OAA, and a-KG involved in metabolic pathways? What is the optimal amount to have? What happens at non optimal amounts?
Pyruvate and OAA are involved in GLYCOLYSIS to help regenerate glucose.
OAA and a-KG are intermediates in the CITRIC ACID CYCLE and help to produce ATP through the oxidation of NADH.
Optimal amount: not too little, not too much
At the wrong amount, we encounter diseases
What are the sources and uses of amino acids?
- digestion of proteins in foodstuff
- intracellular proteolysis
- de novo Synthesis of amino acids
what is intracellular proteolysis? What does it do?
removes misfolded/ old/ damaged proteins
regulates metabolism
controls cell-cycle transitions
what is de novo synthesis of amino acids?
provides us a way to make all “nonessential AA”
this occurs in the liver and individual cells in order to meet needs of different tissues
ex. muscles have a higher need for hydrophobic AA
ex. brain needs glutamine
adjusts energy metabolism
allows cells to respond to stress
needed to synthesis neurotransmitters and nucleotides
digestion of proteins in foodstuffs is important to obtain what? what is a side benefit?
supplies essential (nutritionally essential) amino acids with a bonus of non essential (aka AA we can make) AA
What are the nutritionally essential amino acids?
9 total:
(M) Methiodine
(W) tryptophan
(L) leucine
(H) histidine
(I) isoleucine
(T) threonine
(V) valine
(F) Phenylalanine
(K) lysine
Mother, Why Lie Here In This Very Filthy Kitchen
What are the conditionally essential amino acids and their conditions?
(C) Cysteine - essential when Methionine is inadequate
(R) Arginine - essential during childhood and pregnancy
(Y) Tyrosine - essential when (F) Phenylalanine is inadequate
Come Mom, Yack Further
Rnt you glad you got pregnant?
stress on the cells without adequate amounts
what is our advantage as omnivores?
we obtain amino acids from both plants and plants that animals eat
eat a variety of vegetables to get right proportion of AA
methionine deficiency occurs with lack of animal protein
what is proteolysis?
enzymatic cleavage of proteins
what is the process of digestion and gathering of amino acids?
- saliva: contains proteases from bacteria and white blood cells
- stomach: low pH, uses Pepsin, cleaves Phenylalanine, Leucine, and Glutamate (FLG)
- intestine: protein fragments that cannot refold after the stomach come to the intestine with is at neutral pH and contains neutral proteases (Chymotrypsin, Trypsin, Carboxypeptidase, and Elastase)
if an amino acid goes through all these stages it comes out as well as di and Tri peptides
what is chymotrypsin? how does it work to make amino acids and di and Tri peptides?
an enzyme found in the intestine that cleaves proteins on aromatic AA on the C terminus side
what is trypsin? how does it work to make amino acids and di and Tri peptides?
an enzyme found in the intestine that cleaves proteins on lysine and arginine on the C terminus side
what is carboxypeptidase? how does it work to make amino acids and di and Tri peptides?
an enzyme found in the intestine that cleaves AA off proteins one at a time off the C terminus side
what is elastase? how does it work to make amino acids and di and Tri peptides?
an enzyme found in the intestine that cleaves elastin - a type of protein found in connective tissue
what are proteins not absorbed by healthy intestine?
because proteins are foreign bodies, so our body would respond by making antibodies, therefore, we need to break them down to amino acids and di & Tri peptides that are so small the body doesn’t care
what are zymogens?
storage forms of dangerous enzymes that are excreted into the small intestine which is when they are converted to the active catalysts that break down food
trypsinogen does what?
activated to start digestion
What does enterokinase do?
converts trypsinogen to trypsin
on intestinal mucosal wall
kinase because it starts digestion NOT because it phosphorylates proteins
what does trypsin do once activated?
activates chymotrypsinogen and carboxypeptidase
what is pro-carboxypeptidase?
the starting form that is activated to carboxypeptidase by trypsin
what does carboxypeptidade do?
Removes amino acids one by one off food proteins from the C-termini
What is the trypsin inhibitor
prevents unwanted proteolysis of host cells
since trypsin activates so many enzymes that break down proteins, keeping it inactive when there is no food protein in the intestines allows it to not break down the intestines itself
where is trypsinogen made and stored?
pancreas
describe zymogen synthesis
occurs in pancreas
1. make proteins on ribosomes with certain DNA codes to enter the endoplasmic reticulum
2. small vesicles bud off from ER and go to Golgi apparatus
3. in Golgi apparatus, vesicles get covered in various sugars (to protect the molecules from being digested by other digestive enzymes
describe zymogen activation
proteolytic cleavage
what does zymogen formation do?
prevent autophagy (eating self ) and apoptosis (cell death)
what are the four major digestive proteases in their zymogen and active enzyme form? Where are they stored? At what pH are they optimally active?
Zymogen(Storage location) -> Active Enzyme (Optimal pH)
- Pepsinogen (Stomach) -> Pepsin (pH1-3)
- Chrymotrypsinogen (pancreatic secretion into intestine) -> Chymotrypsin (pH 7)
- Trypsinogen (pancreatic secretion into intestine) -> Trypsin (pH 7)
- Procarboxypeptidase (pancreatic secretion into intestine) -> carboxypeptidase (pH 7)
What is special about Pepsin?
During activation, release of pepsinogen in the stomach
autocatalytic
slow acid catalyzation by stomach acid, when some pepsin is formed, it catalyzes reaction and cleaves many more pepsinogen to form more pepsin
aspartic proteinase: uses aspartic acid carboxyl groups for catalysis
what is protein turnover? What is turnover dependent on?
Protein turnover is the breaking down of older proteins and replacing them
turnover rate depends on metabolic state
(ex. greater degradation when nitrogen intake is low bc cells need AA to make vital proteins )
(ex. not enough Met? body breaks down proteins to generate enough Met)
what are the two major pathways for intracellular protein turnover?
lysosomal/ phagolysosomal pathway
ubiquitin-dependent pathway
Describe the lysosomal/ phagolysosomal pathway.
Occurs in lysosome, ATP dependent pump puts protons into the lysosome, lowering the pH causing the protein to unfold with only positive charges on the surface, making it susceptible to proteolysis by proteins in the lysosome
describe the ubiquitin-dependent pathway
chaperoning mark misfolded proteins that won’t fold properly with ubiquitin (a small polypeptide that joins to poorly folded proteins); ubiquitinated proteins go to proteosomes with built in protease to proteolyze
what are amino acid transporters? where are they located?
AA transporters are located on the top of vili (cilia)
they use sodium ion gradient (which is maintained by ATP hydrolysis) to push amino acid along the concentration gradient
sodium is actively transported into the cell and passively transports down its gradient and moves amino acids into the portal vein/ capillaries
what are symporters?
when a molecule that is already moving helps a stationary molecule move in the same direction it is moving in
describe nitrogen balance in terms of intake and excretion
I = E: True balance
I > E = positive balance
I < E = negative balance
when do we need positive nitrogen balance? when does negative nitrogen balance occur?
positive for growth, pregnancy, wound healing
negative occurs during starvation/ malnutrition/ disease
describe marasmus
a condition associated with insufficiency in protein and energy
wasting away of tissues
when your body uses body proteins for energy needs
severe deficiency in all nutrients
no body fat
describe kwashiorkor
enough calories, but not enough proteins
irritability, slow movement, enlarged liver, abdominal edema/ swelling (caused by insufficiency of albumen in our blood stream
what is transamination
readjustment of amino acids we have consumed in order to get AA we need,
preserve energy of C-N bond;
transfer amino group of an amino acid to PLP to make a new C-N bond and PMP
then alpha keto acid of a different amino acid comes and collects the amino group to form that amino acid and forms the keto acid of the original amino acid
Describe the mechanism of enzyme bound reactions
- dehydration and aldimine forms and is converted to ketamine;
- reverse of 1st using hydrolysis and going from R2-KA to R2-AA and releasing a keto acid
Describe the two important transamination reactions
- alanine: a- ketoglutarate transaminase
alanine to pyruvate
a-KG to glutamate - glutamate: oxaloacetate transaminase
glutamate to a-KG
oxaloacetate to aspartate
what determines the direction of transamination reactions
the concentrations of the metabolites will determine the direction of the reaction
keq = 1 and delta G is very small so enzymes can go in both directions
what amino acids are NOT transaminated?
4
(P) proline and (HP) hydroxypoline (lack amino groups that would be involved)
(K) Lysine (transamination would produce a cyclic toxic non metabolite)
(T) Threonine (dimerize into toxic non metabolite)
TKP HP
Please Hurry Pal, Kill Them
what is glutamate dehydrogenase?
is the main way we oxidate amino acids
in mitochondrial matrix
glutamate to a-KG,
takes in NAD+ and water; produces NADH and NH3
ammonia can be reutilized or disposed as urea
what does NADH and NADPH do?
store electrons that allow cells to manage chemical energy
what does NADH oxidation produce
3 ATP
where does NADH get its energy from?
the breaking of the c-n bond in amino acid oxidation
can GDH be used for other amino acids
yes, most except (PHPKT and H)
couples with transaminases
AA1 + NAD+ + H2O -> a-KA1 + NH4+ + NADH
a-KA1 enters citric acid cycle and NH4+ goes to Urea cycle
what process reoxidizes NADH to NAD+
oxidative phsophorylation
why does NADPH drive reductive amination to form glutamate in the opposite reaction of GDH
because mitochondria rapidly reoxidizes NADH to NAD+, NAD+ is high in concentration while NADH is nonexistent therefore insufficient NADH to go in the opposite direction
high levels of NADPH and low levels of NADP+ so NADPH can de used to drive the reverse reaction
describe the allosteric regulation of GDH
Inhibited with High ATP, GTP, and NADH (favors protein synthesis)
High ADP, high GDP, and free AA’s activate GDH to make more alpha - KG (to make more ATP)
what is the reaction for L/D amino-acid oxidases
utilizes oxygen gad and produces ammonia and hydrogen peroxide
AA + O2 -> a-KA + NH4+ + H2O2
can’t use this as a chief way to oxidize amino acids since high levels of hydrogen peroxide could be toxic
we have BOTH L/D AA Oxidases because D amino acids exists, can form a-KA and harvest more energy
other deamination routes
- cells dominate via hydrolysis and elimination reaction
- glutaminase: catalyzes hydrolysis of glutamine to glutamate (highly distributed in body, ammonia to urea cycle)
- asaraginase: catalyzes hydrolysis of asparagine to form aspartate
- histidinase/ histidine ammonia lyase: catalyzes deamination of histidine to urocanate
why is ammonia in high concentration dangerous?
- ammonia can easily cross membranes and make NH4+/ deplete H+ source and gradients
- depletes a-KG by using it in glutamate dehydrogenase and then using glutamate (what a-KG is made from) to produce glutamine in glutamine synthetase, depleting a-KG even further, which impacts the citric acid cycle and thus the production of ATP causing us to be in a low energy state
what three human enzymes catalyze NH3 assimilation?
- glutamate dehydrogenase
NADPH + NH3 + a-KG -> Glutamate + water + NADP+ - glutamine synthetase
ATP + NH3 + Glutamate -> Glutamine + Pi + ADP + H+ - carbamoyl-phosphate synthetase- 1
2ATP + NH3 + CO2 -> 2HN(C=O)-O-P + Pi + 2ADP + H+
What is the hype around glutamine?
It is the major Nitrogen source to many biosynthetic reactions, acts as a nitrogen shuffle to avoid direct transfer of NH3
allows ammonia to get used as a nucleophile without ever having to touch water/ run the risk of deprotonation
what is gamma glutamyl - p
an essential intermediate between glutamate and glutamine where the phosphate pulls off the O (-) and an ammonia attacks in
what is the ratio between ammonium and ammonia at pH 7.2
100 NH4+ to 1 NH3
What is NH4+ deprotonation driven by?
ATP dependent enzyme conformation change that moves guanidinium group of a nearby arginine to allow electrostatic repulsion from NH3
What would happen if glutamine synthetase and glutaminase were in the same compartments in the cell?
it would be futile, just using energy and water
avoid by keeping enzymes in different compartments.
where does glutamine synthetase occur? where does glutaminase occur?
GS (making glutamine) : cytosol
glutaminase(make glutamate and ammonia) : mitochondria
describe carbamoyl phosphate synthetase 1
main ammonia assimilating reaction in mitochondria
highly energy dependent
taks 2 ATP + HCO3- + NH3
produces a carbamylated metabolite + ADP + 2 Pi
2 steps
1. phosphorylate HCO3-, make intermediate, which ammonia attacks (there is enough around since this is near the mitochondria) and phosphate leaves
2. phosphorylation of ammoniated intermediate (Carbamate) to produce carbamoyl-P
describe the role carbamoyl-phosphatase 2
CPS-2 hydrolyzes glutamine and uses a transfer tunnel to get the ammonia to the biosynthetic subunit while glutamate left over acts as a lid to prevent water in the tunnel (also moves carbamate in tunnel)
in cytoplasm
avoids toxicity in ammonia
beneficial since it can deprotonate NH3 exactly when and where needed
glutamine dependent
what are some properties of glutamine dependent enzyme reactions?
exhibits low Km / high affinity for glutamine
essential -SH group generates gamma glutamyl thioester that occupies active site permitting NH3 transfer
the series of reactions:
amidohyrolase site (ammonia cleaved) -> transfer tunnel -> biosynthetic site
compare and contrast CPS-1 CPS-2
CPS 1: in mitochondria, uses ammonia, high affinity for NH3 and no affinity for glutamine, part of urea cycle, has an activator (N-acetyl-glutamate)
CPS-2: in cytosol, uses glutamine, no affinity for NH3, high affinity for glutamine, part of pyrimidine nucleotide biosynthesis
How do different species excrete nitrogen?
Fish = ammonotelic = NH3
Birds = uricotelic = uric acid
mammals = ureotelic = urea (primarily, but some uric acid and creatine)
amount excreted depends on intake
When does Gout occur?
when too make uric acid is produced
what is the principal site of NH3 detoxification? where do they occur in the cells?
liver, a bit in kidneys
cytosolic compartments and mitochondrial compartments
HCO3- + NH4 + 3 ATP + Aspartate + H2O -> UREA + 2ADP + 2 Pi + AMP + PPi + Fumarate + 5H+
Produces urea and a lot of protons (which help control body pH)
Urea cycle
IN MITOCHONDRIA
1. make carbamoyl phosphate
2. Ornithine Transcarbamoylase: CP + Ornithine (looks like lysine but one CH2 short, not found in proteins in normal condition) -> citrulline
IN CYTOSOL
3. Argininosuccinate synthase: citrulline + ATP -> argininosuccinate
4. Argininsuccinate lyase: argininosuccinate -> arginine + Fumarate
5. Arginase: arginine (hydrolyzed) -> Ornithine(goes back to mitochondria) + UREA
CO2 made by citric acid cycle is hydrated to HCO3- which is used to make carbamoyl phosphate
NH3 is released from FDH
ATP made from ADP + Pi (driven by NADH formed by GDH via Electron Transport Chain and Oxidative Phosphorylation
how does diet relate to the urea cycle?
a diet high in protein has amino acids that stimulate glucagon which stimulates biosynthesis of urea cycle enzymes
this reduces ammonia load and increases pyruvate, OAA< & a-KG for gluconeogenesis (remaking glucose)
what is the relationship between CPS 1 and glutamate?
when amino acid catabolism increases glutamate and N-acetlyglutamate levels rise; N-acetylglutamate allosterically activates CPS 1 which starts the Urea Cycle
what are 2 powerful regulators of the urea cycle?
arginine and glutamate
when high NH3 load, they form N -acetylglutamate
describe N-Acetyl Glutamate synthase
glutamate + acetyl CoA -> N-Acetyl Glutamate + CoA
NAG = essential activator of CPS 1/ Urea Cycle
what does NAG Synthase deficiency result in
hyperammonia
how is glutamate and arginine related to NAG/NAGS/ Urea Cycle
Glu substratte for NAG
Arg activates NAGS allosterically
High Glu and Arg concentrations are indicators of high amino acid content
NAGS produce NAG with activates CPS 1 with starts the Urea Cycle`
what is the liver acinus
a special region in the liver that allows us to remove ammonia from both arterial (hypatic artery) AND venus (portal vein) blood
blood passes through this region which is rich in urea cycle enzymes
what are the perivenous scavenger cells
any blood passing through the liver acinus that still has ammonia goes through the perivenous scavenger cells to mop up the rest so when blood moves on it is ammonia free
**Glutamine synthase enzymes (high affinity of NH3)
Connect liver acinus and perivenous scavenger cells
liver acinus: low affinity for NH3 but high capacity to make urea
perivenous scavenger cells: high affinity for NH3 but low capacity to make urea; utilizes ATP to make glutamine from it and supply glutamine to the body
describe the synthesis/ function of the nonessential amino acid arginine.
made in the urea cycle (glutamate -> ornithine -> citruline -> argininosuccinate -> arginine
can be brought in through diet
source of vascular dilator (opens blood vessels/ lowers blood pressure) nitric oxide
what is creatine
creatine is the substrate for creatine kinase to make creatine-P
what is the importance of creatine-P
acts as a reservoir of phosphorylation groups so ADP can be made back into ATP when ADP concentration is high
can rearrange to make creatinine
what is creatinine
break down product of creatine-P in our muscles
produced at a fairly constant uncatalyzed rate
yield depends on muscle mass
clearance rate tells us how well kidney is working
what are the different processes of glutamate synthesis?
- transamination
- reductive amination (GDH)
- hydrolysis of glutamine to glutamate (glutaminase)
how is glutamine made
exclusively glutamine synthesis reaction
(not the reverse of glutaminase because it would require a deadly amount of ammonia)
describe the synthesis of the nonessential amino acid aspartate
- transamination
- hydrolysis of asparagine
describe the synthesis of the nonessential amino acid asparagine
using asparagine synthetase (2 site enzyme connected by tunnel),
aspartate + glutamine, + ATP -> Asparagine + glutamate + AMP
has a tunnel where ammonia is transferred through to get put on aspartate
one site hydrolyzes Gln to produce NH3 which travels through the tunnel and attacks an aiready established beta-aspartyl-amp to make asparagine and AMP
describe the synthesis of the nonessential amino acid alanine
only by transamination
pyruvate + glutamate -> alanine + a-KG
describe the alanine shuttle
inter organ transfer for ammonia nitrogen as alanine to prevent toxicity
describe the synthesis of the nonessential amino acid proline
in steps
1. glutamate -> through reductase (&NADH) -> carbonyl instead of carboxyl acid on end
2. cyclase/ dehydrogenase
3. reductase (NADH) -> proline
describe the synthesis of the nonessential amino acid ornithine
glutamate semi aldehyde intermediate in forming protein can transaminase into ornithine
describe the synthesis of the nonessential amino acid hydroxyproline
occurs within collagen
by prolyl hydroxylase + iron (+2)
prolyl residue + O2 -> hydroxyprolyl reside + CO2
every 300 times through cycle, iron gets oxidized and kills the enzyme so deactivated prolyl hydroxylase form Fe(III) which is reduced by vitamin C/ ascorbic acid to get Fe (II)
absence of vitamin C leads to unstable collagen
describe the synthesis of the conditionally essential amino acid tyrosine
phenylalanine hydroxylase (2 steps)
Phe + NADPH + O2 -> Tyr + NADP+ + H2O
O2 gets The to Try, NADPH gets the enzyme back to the original state
describe phenylketonuria (PKU)
high serum phenylalanine and high urinary phenylpyruvate (forms upon transamination)
occurs when you cannot make tyrosine
recessive genetic condition
causes damage to neurons
treatable through control of diet and low Phe
describe the synthesis of the conditionally essential amino acid cysteine
SAM = S-Adenosyl-methionine
Methionine + ATP -> SAM (hydrolyzed) -> homocysteine (reacts with serine ) -> cystathionie (Breaks asymmetrically) -> cysteine + a-Ketobutyrate
how are nucleotides provided to our cells?
- dietary intake of rna/ dan that are degraded via nucleases
- salvage of bases/ reusing purine bases by form nucleotides
- de novo synthesis: make out own, especially in rapidly dividing cells
what does salvage and de novo synthesis of nucleotides require?
phosphoribosyl-pyrophosphate (PRPP) - an activated sugar intermediate
describe PRPP role
a base can attack PRPP and attach at alpha position
Base + PRPP -> Nucleoside 5’P + PPi
describe the pathway for the pyrimidine biosynthesis
- add glutamine and ATP via CPS2
- carbamalate the aspartate via carbamoylation
- dehydrate driven by election delocalization to close and form a cyclic structure
- remove 2 hydrogens by NAD+ to NADH and one proton leaves as is and replace with double bond
- react PRib-PP with pyrimidine phosphoribosyl transferase to connect ribose to ring
- OMP Decarboxylase
(rate enhancement is 1.1 10^17, t1/2 would be 3 billion years )
how can we form UTP from UMP?
Phosphorylation x2
describe CTP synthetase.
starting with UTP and undergoing a glutamine dependent reaction with a transfer tunnel and ATP, we can form CTP which has a NH2 on the nitrogen base rather than double bond O
what are the two types of CTP Synthase? what is their relationship
CS-I: essential for CDP - diacylglycerol formation (lipids)
CS-II: rate limiting enzyme in biosynthesis of pyrimidine precursors of RNA and DNA; activated by GTP; balance amounts of purine and pyrimidine nucleotides
isoforms
what can an insufficiency in CS-II related to>
impact on cell growth and development
where is dTMP derived from?
dUMP
describe dTMP synthesis
*synthase ONLY works from the deoxy form
1. dihydrofolate reduced to tetrahydrofolate via NADPH -> NADP+
2. tetrahydrofolate reacts with serine to form methylene-THF (and glycine) with serine hydroxymethyl transferase
3. methylene-THF + dUMP via thymidylate synthase forms dTMP (and dihyrdrofolate which starts the reaction again)
how is cancer chemotherapy related to the synthesis of dTMP
if any step is block, dTMP will not be produced and it will stop DNA synthesis; allows doctors to stop spread of cancer DNA
use methotrexate which is folate like and reduce dihydrofolate and slow/ stop cycle
how does fluorouracil impact dTMP synthesis?
fdUMP would have the fluoro group where the methyl group should bind, thus blocking the synthesis of dTMP and making the molecule get stuck in enzyme
what molecule does purine biosynthesis begin with?
PRPP and builds purine ring on ribose ring
what provides one carbon transfers
N10-formyl-THF
what is inosine 5’-P
intermediate of purine nucleotide that tautomerizes too freely to be apart of DNA
describe the pathway of purine biosynthesis
- PRPP through glutamine hydrolysis to add ammonia in place of 2 PP *use transfer tunnel
- activate glycine with phosphorylation and attack int. 1
- formyl-THF reacts with int. 2 to add C=O to amino group (of glycine)
- replace C=O from glycine with C=N by (1)glutamine hydrolysis to phosphorylate C=O (2) NH3 Transfer (3) NH3 displaces Pi
- Ring closure by phosphorylating and losing oxygen; end with 5 membered ring
- carboxylation (bicarbonate) and phosphorylation (ATP) via attack on carboxyl-P int.
- replace O from bicarbonate by phosphorylating O and reacting with aspartic acid to add Succ-N
- trans elimination to be left with NH2
- formyl-transfer onto ammonia attached to a C in the 5-membered ring
- ring closure driven by resonance that kick out water and form 6 membered ring and produce IMP
what is the only know difference in purine metabolism between bacteria and mammals?
where the formyl-THF attacks (either ammonia group from aspartic acid or from glutamine
How can IMP be converted to AMP
- tautomerizes to have OH at C6; react with GTP (phosphorylate) and aspartate (displace phosphate with amino group) to form adenosuccinate
- trans elimination of fumarate
occurs at high levels of GTP
How can IMP be converted to GMP
- react with NAD+ and water to add oxygen and get Xanthosine 5’-P (redox reaction)
- phosphorylate with ATP and add glutamine to replace oxygen with NH2 *use transfer tunnel
ATP for energy
What does high AMP do to nucleotide synthesis?
stops IMP converting to it and IMP concentration rises and goes toward XMP
what does high GMP do to nucleotide synthesis?
shuts off that pathway and IMP converts to AMP more readily
what happens if both AMP and GMP have high concentrations?
first reaction of PRPP to p-Rib-NH2 is inhibited and turns off PRPP synthesis
what enzyme phosphorylates AMP?
adenylate kinase
how does ADP convert to ATP
oxidative phosphorylation
how is GMP phosphorylated
GMP Kinase
how does GDP go to GTP
nucleoside diphosphate kinase
what happens when adenine nucleotides are in excess?
AMP Deaminase converts AMP to IMP and drives reaction to form more GMP
what happens when guanine nucleotides are in excess
GMP Reductase converts GMP to IMP to produce more AMP
describe purine salvage pathway
start with PRPP and capture either hypoxanthine to form IMP or capture guanine to form GMP
what purine is not salvaged by HGPRT and why
adenine because it is in such high abundance that if HGPRT could salvage it, GMP and IMP would never form
what does adenine deaminase do
convert adenine to hypoxanthine when concentration levels are very high
describe purine degradation
GMP -> dephospho rylation -> phosphorlysis (guanine) -> hydrolysis (xanthine) -> xanthine oxidase -> Uric acid/ sodium rate
AMP -> deamination (IMP) -> dephospho rylation (inosine) -> phosphorolysis (hypoxanthine) -> oxidation (xanthine) -> xanthine oxidase -> uric acid/ sodium rate
what is the condition caused by excess uric acid? describe it.
gouty arthritis
uric acid accumulats in joint and as it works, crystals form which white blood cells attack with leads to inflammatory response/ pain
how can you treat gout?
using an analog of hypoxanthine called allopurinol that is a xanthine oxidase inhibitor; xanthine and hypoxanthine excreted in urine
what does UDP and UTP specificity tell us?
we had a transition from RNA to DNA
what is the key role of RNR
make deoxynucleotides in the right amounts so DNA polymerase function is not interfered with; concentrations cannot be in excess AS deoxyforms
what happens if a nucleotide is in excess
it binds to RNR to inhibit formation of its deoxy form
how does RNR achieve balanced production
by changing catalytic efficiency with each substrate and preventing overproduction of any deoxynucleotide
describe the synthesis of the nonessential amino acid serine
starting with 3-phosphoglycerate
