Nitrogen, AAs, and Ntides Flashcards
Role of Aminotransferases
Transfer NH3 from AA to alpha-ketoglutarate to turn it into glutamate (and AA become alpha-keto acid)
Aspartate Aminotransferase
Unique aminotransferase that transfers NH3 from glutamate to OAA, forming aspartate and alpha-ketoglutarate
Aspartate Aminotransferase Cofactor
Vitamin B6 Pyridoxal Phosphate transfers amine in pyridoxamine phosphate form
Oxidative Deamination
Glutamate Dehydrogenase catalyzes glutamate conversion to alpha-ketoglutarate w/ release of free NH3
Ammonia Transport and Release to/in Liver (3)
Glutamine synthetase adds free NH3 to glutamate in most tissues to create glutamine
Glutamine carries it through blood to liver
Glutaminase and glutamate dehydrogenase remove the two amines in that order to yield glutamate then alpha-ketoglutarate
Urea Production Cycle (5 long)
Carbamoyl phosphate synthetase I adds CO2 and NH3 (first two sources of stuff for urea) to form carbamoyl phosphate
Carbamoyl phosphate adds to Ornithine to form Citrulline which can be transported out of mt matrix
Aspartate (source of urea’s 2nd N) adds to Citrulline to form arginosuccinate
Fumarate leaves to form Arginine, which has guanidino group head
Guanidino group leaves and becomes urea, leaving ornithine which can be transported back into matrix
N-Acetylglutamate (formation and function)
Formed from Arginine-activated Acetyl CoA adding to glutamate
Required to activate carbamoyl phosphate synthetase I for urea production
Source of Ammonia in Urine
Glutamate dehydrogenase in kidneys
Hyperammonemia (cause, symptom, treatment)
When you have liver disease bc liver is making urea
High glutamine levels in blood
Phenylbutyrate converts into phenylacetate, which can combine w/ glutamine to form phenylacetylglutamine which will be excreted out
2 Exclusively Ketogenic AAs
Leu and lys
4 Gluco and Ketogenic AAs
Tyr, Ile, Phe, and Trp
Degradation of Asn and Asp
Asn converted to Asp converted to OAA (aspartate aminotransferase)
Pro, Arg, His, and Gln Degradation
Feed into glutamate can turn into alpha-ketoglutarate for glucogenic effects
Ala Degradation
Gives NH3 to alpha-ketoglut (becomes glutamate) to become pyruvate
Gly and Ser Degradation
Gly becomes ser via THF-producing rxn, and ser becomes dehydrogenated to pyruvate
Phe and Tyr Degradation (2)
Phenylalanine hydroxylase converts Phe to Tyr via Tetrahydrobiopterin putting -OH on phenyl ring
Tyr converted to fumarate and acetoacetate
Degradation of Leu, Val, and Ile (3 rxns and 2(3) products)
Transaminated to alphaketoacids
Oxidative decarboxylation to FAs
FAD-linked dehydrogenation
Leu is ketogenic, forms acetoacetate + acetyl CoA
Val and Ile are glucogenic, form succinyl CoA
Maple Syrup Urine Disease
Defect in alpha-ketoacid dehydrogenases breaking down the alpha-ketoacids formed from leu/val/ile degradation
Met Degradation
Generates SAM which is used as methyl donor for chromatin remodeling/DNA, then converted to Homocysteine which can be reconverted to Met + THF or Serine added to form Cysteine
Homocysteine Clinical Consideration
Higher levels correlate w/ cardiovascular problems
THF Use
AA and Purine Synth
Main Function of Tyr
Hormone Production
Dihydrobiopterin (BH2) Reductase Deficiency (action, and 3 clinical effects, and treatment note)
Can’t reset BH2 to tetrahydrobiopterin (BH4), causing phenylketouria by messing up phenylalanine hydroxylase
also messes up tyr hydroxylase production of DOPA/CATs and
trp hydroxylase 5-HT production
Difficult to treat bc even if supplement w/ BH4 it can only be used once
3 Causes of Phenylketouria (most to least common)
Phenylalanine hydroxylase deficiency
Dihydrobiopterin Reductase Deficiency
GTP Cyclohydrolase Deficiency - can’t produce BH2
2 Biochemical Effects of Phenylketouria (2.6)
Can’t produce tyr from phe, so miss tyr products like melanin, CATs, and fumarate and acetoacetate
Excess phe converted to phenyl pyruvate and then have buildup of toxic organic acids
Major Clinical Effect of Untreated Phenylketouria
Progressive severe retardation
Albinism Cause
Melanin deficiency from enzyme deficiency to convert bw tyr and melanin
Homocystinuria
Cystathione Beta-Synthase Deficiency can’t degrade homocysteine
Alkaptonuria
Homogentisic Acid Oxidase deficiency causes urine to turn black from oxidation
5 Donors to Purine Synth (& what they donate)
Glutamine - 2 Ns Aspartate - 1 N Glycine - Backbone of 2Cs and 1N N-formyl-THF - 2Cs CO2 - 1C
First Step in Base Synthesis
PRPP Synthetase creates 5-Phosphoribosyl-1-pyrophosphate (PRPP) from Ribose 5-P and ATP->AMP
Purine Synthesis Mech (general point and 8 steps)
Start w PRPP and build ring around it Glutamine adds 1st N group Glycine adds 2C 1N backbone N-formyl-THF adds C Glutamine adds 2nd N group CO2 adds C Aspartate adds, then leaves N group N-formyl-THF adds 2nd C Dehydrated to IMP
Methotrexate
Binds and inhibits DHF reductase, preventing reset of THF
IMP
Differentiates into AMP and GMP
IMP into AMP
Aspartate adds, then leaves just NH2
IMP into GMP (2)
Double bond oxidized to carbonyl, then exchanged for NH2 from glutamine
3 Donors to Pyrmidine Synth
Aspartate - 1N and 3 Cs
Glutamine - 1N
CO2 - 1C
Pyrimidine Synth (major point and 6 steps)
Synthesize ring first then add to PRPP
Carbamoyl phosphate synthetase II creates carbamoyl phosphate from Gln/CO2/ATP
Aspartate adds
Cyclization
Oxidization into orotate
Orotate added to PRPP to create orotidine 5’-monophosphate
Decarbox to UMP
CTP Synthesis
CTP Synthetase adds NH2 from Gln to UTP
Nucleoside Diphosphate Synthesis
NMP + ATP -> NDP + ADP
Salvage Pathways
When bases from diet can be directly added onto PRPP avoiding pathway
Ribonucleotide Reductase (2)
Turns ribonucleoside into deoxyribonucleoside via thioredoxin (red-> oxidized)
Thioredoxin reset by the reducing equivalents NADPH
Synthesis of dNTP (except TTP)
NDP->dNDP->dNTP
Synthesis of (d)TTP
UDP->dUDP but don’t need for DNA, so ->dUMP and then thymidylate synthase catalyzes to (d)TMP->TDP->TTP
Purine Degradation (3 steps)
AMP and GMP lose ribose 1-P to form hypoxanthine and guanine, respectively
Which then converted to xanthine
Xanthine oxidized to uric acid
Gout
Uric acid kept at very high blood concs, so if have problem w/ overproduction or underexcretion it will precipitate and collect in/swell joints
Treatment of Gout (w/ 2 different causes of gout)
Overproduction of uric acid - use allopurinol which inhibits xanthine oxidase
Underexcretion - not really treatable, usually caused secondary to some other condition
