Proteins III Flashcards
Sulfur aa
cysteine
methionine - essential
cysteine can form disulfide crosslinks with another cysteine to form
cystine
Methionine degradation –> cysteine synthesis
PATHWAY?
MET –> SAM –> SAH –> HOMOCYSTEINE –> CYSTATHIONE –> CYSTEINE
What amino acid is included in the synthesis of cysteine from methionine (complexed with homocysteine?)
serine
We can also regenerate methionine from homocysteine - what two coenzymes are required for this?
THF
VitB12
The methyl group is transferred from THF to B12 to homocysteine
Enzyme important in initial production of cysteine from homocysteine?
cystathione-Beta-synthase
this enzyme makes cystathione - an intermediate - and requires VitB6 derivative PLP
Mutations can lead to hyperhomocysteinemia or homocystinuria
hyperhomocysteinemia can be due to?
low levels of folate, B6, or B12
Hyperhomocyteinemia can lead to
vascular disease
Folate, B6, and B12 are all important in methionine breakdown via homocysteine metabolism, but which are important for regenerating methionine and which are important for generating cysteine
B12 and folate are important for regenerating methionine
B6 is important for generating cysteine
defect in cystathionine beta-synthase leads to?
mental retardation, osteoporosis, and vascular disease
cysteine becomes essential
can treat with B6 if residual activity to try and force
Cysteinuria -
kidney stone and renal failure due to defect in transporter of cysteine which leads to crystallization
cysteinuria treat with
acetazolamide - makes cysteine more soluble
treat homocystinuria with?
B6 to force
and cysteine become essentia
treat hyperhomocysteinemia with?
B12 and folate and B6
cysteine become essential
plasma levels of homocysteine are directly correlated with?
CV mortality
associated with vascular disease - pro-inflammatory
impaired wound healing
cancer (Cervical)
SAM is similar to
ATP
energy storage unit
SAM has charged what?
charged sulfur that is highly reactive
methyl donor
We know SAM is a methyl donor, what important hormone does it methylate to yield other important hormone
methylates norepinephrine –> epinephrine
We know SAM is a methyl donor, which base does it methylate?
cytosine residues in DNA - important for epigenetics
SAM is a methyl-donor - who else is a methyl donor (hint: derivative of micro-nutrient)
THF
What is the name of the enzyme that produces THF from folate?
dihydrofolate reductase (DHFR)
Why would an oncologist be interested in the enzyme dihydrofolate reductase (DHFR)
Because methotrexate (A cancer medication) inhibits this enzyme and thus inhibits the formation of THF from folate - THF is important in DNA synthesis so block cell proliferation
Glutathione (GSH) who is in the middle
cysteine - with its lovely sulfur
What does GSH do?
redox buffer
keeps Fe in Fe2+ state (active hemaglobin)
protects against ROS
Cofactor for muchos enzymes
enables proper disulfide bridge formation (Along with PDI)
Glutathione peroxidase
Mutations lead to high BC risk
Glutathione reductase
Mutations problematic for heme
Glutathione S-transferase - conjugates to other agents
Detox (ROS)
Upregulated in tumors
Trp metabolism
pyruvate or acetyl-CoA
Trp makes?
seratonin
melatonin
niacin (b3)
Trp cofactor
BH4
Phenylalanine hydroxylase mutations –>
phenylketonuria
PKU toxic byproducts
phenylpyruvate
phenylacetate
phenyllactate
Tyrosine yields?
catecholamines (NTs)
melanin
Errors in tyrosine metabolism can lead to?
Parkinson
Depression
Albinism
Parkinson’s treat with Dopa and MAOs why?
Because MAO breaks down catecholamines (DOPA, Dopamin, Norepi, Epi, serotonin)
Decarboxylation of numerous amino acids –>
biological amines (serotonin, catecholamines, GABA, Histamine)
