Protein- Metabolism Flashcards
Essential or Nonessential - Phenylalanine
Essential
Tryptophan hydroxylase
converts tryptophan to 5-hydroxytryptophan
an intermediate in the synthesis of serotonin.
requires BH4
Essential or Nonessential - Glycine
Nonessential - glucose
how does bilirubin get to the liver
it is only slightly water soluble so binds noncovalently to albumin.
where is fumarate formed in urea cycle?
argininosuccinate lyase to convert arginosuccinate into fumarate and arginine.
which amino acids are degraded into alpha-ketoglutarate
Arginine, histidine, glutamine, and proline –> glutamate –> alpha ketoglutarate
Ubiquitination
Series of 3 enzymes E1-3 add ubiquitin to lysine (poly ubiquitin) to target protein for degradation by proteosome.
Requires ATP
Proteosome unwinds protein and degrades them into Amino Acids.
mycophrenolic acid
drug that reversibly inhibits GMP formation
prevents T and B cell proliferation and graft cell rejection.
Cytosine Arabinoaside
inhibitor of DNA polymerase
5’ Nucoleotidase
removes the phosphate in purine degradation
what is SAM
a carbon donor and high energy storage unit.
similar to ATP except that a methyl group replaces the phosphate.
essential for methylation of protein,nucleic acids, lipids,c carbs, epineprine to NE
Epigenetics host defense
Cancer
treats depression.
Bilirubin-Glucuronyl Tranferase
facilitates the conjugated of bilirubin in the hepatocyte.
bilirubin –> bilirubin diglucuronide
This is called conjugation
converts UDP glucuronic acid to UDP
delta-Aminolevulinic acid synthase
glycine + Succinyl CoA (from TCA) condensation to form –> Aminolevulinic Acid (ALA)
in Heme Synthesis
requires PLP, rate limiting step of porphyrin biosynthesis
in MITO
formation of urogilinogen
hydrolyzation of bilirubin diglucoruonide in gut to yeild urobiolinogen.
some is recycled back to enter portal blood.
what is the intermediate fromed in purine synthesis?
IMP
Regulation of Urea Cycle
1) aminotranaminases with [Prod] & [reactants]
2) Carbomyl phosphate synthase I
3) [Glutamate], [alpha ketoacid] and [NH3]
4) Glutamate dehydrogenase and ATP vs ADP levels
R group type - Tryptophan
NP
NO synthase
occurs in nerve and muscle
converts Arginine into cirtulline and forms NO in the process
requires tetrahydrofolate and NADPH
CTP synthetase
converts UTP to CTP with addition of glutamine and ATP
R group type - Lysine
Basic
Porphyria
rare, inherited defect in heme syntehsis resulting in accumulation of porphyrins
which portion of urea cycle does asparate enter?
arginosuccinate synthase
Essential or Nonessential - Asparagine
Non essential - synthesized from glucose
Pyrimidine synthesis starting materials
2ATP
CO2
Glutamine
Pyridoxal phosphate
PLP
derivative of Vitamin B6 that serves as coenzyme for aminotransferases.
holds the NH3 during transfer to form a Schiff base - covalent link
branched Amino acids
Valine, Isoleucine, and leucine
Glutathione
modification of amino acids
1) redox buffer to maintain proteins in reduced forms and regulate enzymatic activity
2) cofactor for glutathione transferase
3) reduces H2O2 for protection form ROS
4) proper disulfide bond formation in protein folding
5) facilitates the conversion of methemoglobin into active hemoglobin
Glutathione peroxidase
converts GSH to GSSG and also H2O2 to H2O
leucine ketogenic or glucogenic
ketogenic
Carbomyl phosphate synthase II
first step in pyrmidine synthesis
CO2 and glutamine + ATP –> Carbomyl phosphate
occurs in cytosol.
hydroxyurea inhibits what?
UDP –> dUDP
when is PRPP added in pyrimidine synthesis
almost until the end. added to Orotic acid!
How many ATP are required in Urea Cycle
3 ATP
Guanase
converts guanine –> xanthene (removes NH3)
Essential or Nonessential - Serine
Non essential - synthesized from glucose
R group type - tyrosine
polar
Essential or Nonessential - Tryptophan
Essential
Homocystinuria
deficiency in cystathione beta synthase to lead to build up of homocysteine
Hydroxylproline
post translational modification of Porline by
Prolyl Hydroxase.
Responsible for hydrogen bonding between and within collagen triple strands.
R group type - Serine
polar
which amino acids have sulfur
only 2
methionine
cysteine
which amino acids are degraded into fumerate?
phenylalanine –> tyrosine
Tyrosine and asparate –> fumerate
Acivicin
Gln analog, inhibitor of NT synthesis
Essential or Nonessential - Alanine
Non essential - synthesized from glucose
Mutations in glutathione peroxidase
increase breast cancer risk
What are the components of glutathione?
Glutamate + Cysteine + glycine
Pyrimidine breakdown
base ring is opened (unlike purine) and products are succinyl coA, Malonyl CoA, Acetyl-CoA.
water soluble.
R group type - Threonine
polar
what amino acids are synthesized from TCA cycle
Alpha ketoglutarate - Glutamate and glutamine. Glutmate forms proline and arginine.
OAA- asparate and asparigine.
Isoleucine ketogenic or glucogenic
both
Thyroid hormone synthesis
Tyrosine converted to T4 - thyroxine and T3 Tridothyronine.
Salvage pathways
used to reassemble purine and pyrimidines without havign to undergo denovo synthesis
Azidothymidine
AZT
inhibitor of Viral Polymerase
thymidylate synthase
converts dUMP into dTMP
requires THF
Phenylkeotonuria
deficiency in phenylalanine hydroxylase to cuase build up of phenylalanine and deficiency in tyrosine.
R group type - Valine
NP
Essential or Nonessential - Valine
Essential
Phenylalanine hydroxylase
degradation of pheylalanine to tyrosine.
Requires NADH and BH4
how is homocysteine converted to cysteine
Hcy condenses with SERINE to form cystathionine.
Cystathionine is then converted into cysteine.
what amino acids are synthesized from glucolysis
Serine, Cysteine, glycine,
Alanine (pyruvate)
reduced form of cysteine
single cysteine
Ornithine transcarboamylase deficiency
buildup of ornithine and shortage of citrulline.
where is ATP required in Glutathione synthesis
in both steps - requires 1 ATP
Adenine Phosphoribosyltransferase
purine salvage
converts adenine into AMP with addition of PRPP
R group type - Cysteine
Polar
Heme Synthesis
occurs in the liver and erythrocyte producing cell of bone marrow
! synthesis rate is variable depending on cellular heme pool in live,r but constant in erythroid cells.
From Glycine and succinyl CoA
combination of in mito (initial rxn and last three steps of porphyrin formation) and cyto
Ribonucleotide reductase
enzyme that converst ribonucleotides to deoxyribonucleotides.
requires thioredoxin (2SH) to be oxidized to thioredoxin (SS)
inhibited by dNTPs
how is GABA formed?
Glutamate – (Glutamate decarboxylase) –> GABA
requires PLP
oxidized form of cysteine
double bond - disulfide bond.
Purine Synthesis begins with a…
Ribose 5 phosphate
Transamination
transfer of an amino group from an Amino Acid to alpha-ketoglutarate.
Reversible
located in the cytosol as a dimer with two active sites
where is the nitrogen input in the urea cycle
Ammonia
Asparate
Homocystinuria
defect in cystathionine beta synthase activity with large elevations in homocysteine levels.
associated with mental retardation, osteoporosis, vascular disease (premature thromboci complications before 30 yo)
Glutamine Phosphoribosyl pyrophosphate amidotransferase
PRPP –> 5’-phosphoribosylamine in purine synthesis
Glutamine is added.
Activated by PRPP
inhibited by AMP, GMP, and IMP
the most important regulatory step in purine synthesis
which amino acids are degraded into succinyl Co-A
Valine, threonine, isoleucine, methionione –> propionyl-CoA –> Methylmalonyl CoA –> succinyl CoA
Hydroxylysine
post translational modification of lysine by lysyl hydroxase
responsible for covalent crosslinks within collagen
Valine - ketogenic or glucogenic
glucogenic
Lead and heme synthesis
inhibits delta-aminolevulinat dehyratase and ferrochelatase.
Allopurinol
inhibition of xanthine oxidase
treatment of gout (uric acid build up -not water soluble)
Pepsin
Proenzyme: endopeptidase that is activated by Hcl
Aspartic Protease
Leaves after terminal of aromatic Phe, Trp, Try
Essential or Nonessential - Proline
Non essential - synthesized from glucose
Specificity of ubiquitination
there is more E3>E2>E1 that leads to specificity
S Adenosylhomocysteine
SAH is formed by hydrolysis of SAM and transfer of methyl group to methyl acceptor.
Methotrexate
inhibits dUMP –> dTMP
AMP is formed via
IMP combining with Aspartic acid to form adenylsuccinate
glutaminase
enzyme that converts Glutamine + H20 --> glutamate and NH3 found only in hepatocytes other source of NH3 for urea cycle besides glutamate dehydrogenase also found in kidney epithelial cells
hyperhomocysenemia
due to low folate, VitB6 and vit B12
promotes oxidative damage, infalmmation, endothelial dysfunction.
vitamin supplementtion reduces these levels.