Aa metabolism Flashcards
Carbon Chains Enter Metabolic Pathways
Glucogenic= feed into glycoclysis & Krebs
- pyruvate= ala, cys, gly, ser, met
- Oxaloacetate= asp, asn
- a ketoglutarate= arg, glu, gln, his, pro
- succinyl coA= met, val
Carbon Chains Enter Metabolic Pathways
Ketogenic- produce acetyl Co A
- leu & lys
Carbon Chain enter Metabolic Pathways
Both
Produce precursors of gluconeogensis & ketone boides
Ile, Phe, tyr, trp, thr
Low Carb/ High Protein & Fat Diet
Glucose essential for brain!
Breakdown protein to supply gluc
Ketone bodies from ketogenic & mixed glucogeneic/ketogenic aa= acidosis
Diuresis= loss of H2O & minerals
Can get shock, coma, death
Problems with Diet
Not permanent
Lose lean body mass for gluconeogenesis
Low gluc with higher calorie diet= slower weight loss
Glucose: Pyruvate Transaminase GPT
or
Alanine aminotransferase ALT
Cytosolic
Released after minor damage to hepatocytes
Glutamate: Oxaloacetate Aminotransferase GOT
or
aspertate aminotransferase AST
in heart & skeletal m., liver
Diagnostic purposes
Acute lymphoblastic luekemia ALL
All cells express little Asn synthase but need Asn for nt syn
Injection of asparginase destroys Asn in blood
Folate
- Essential nutrient, Vit M
- Dihydrofolate reductase converts dietary folate into THF
- THF used as carrier of C1 bodies in metabolism
- C1 bodies come from aa metabolism & needed for nt syn!
- All C1 conversion rxns are reversible!
Sulfphonamides
- Broad spectrum antibiotic
- pro drug gets converted to sulfanilamide in body
- Sulfanilamide has no effect on human folate metabolism but stops bac from syn it
Trimethoprim
- inhibits dihydrofolate reductase- enz converts folate into THF
- Drug given w/ sulphonamide
Methotrexate MTX
- inhibitor of dihydrofolate reductase
- works on mammals
- Treats cancer & in lower doses- autoimmune disease
Ala & Ser cycle
Exertion= lactic acid production & NH4+
Detox in liver
Form ala to transport both products in blood w/o toxicity
Ser can convert to pyruvate
Glu, Gln, Asp & Asn
Enter Krebs
Glu & Asp produce Gln & Asn by carboxylic amidation
Gly, Thr & Ser
Irreversible rxns
Glycine cleavage enz def= non ketotic hyperglycinemia.
- AR
- severe neuronal def, can be fatal.
Excess glycine conversion= oxalate (forms kidney stones)
Met & Cys
Met makes SAM (C1 carrier)
If not enough folate, homocysteine accumulate leading to vascular complications.
- more homocysteine than needs to be converted to Met, condensed to cystathionine.
- Cystathionine synthase- defect AR leads to homocysteinuria.
Excess folate can maks pernicious anemial from B12 def but neurological iplication still present!
Homocysteine–> Met need B12!
Met syntahse needed for regen of folate & met. If both supplied, megaloblastic anemia & choline syn defect won’t occur. Only problem= homocysteinuria.
Methylmalonyl co A mutase blocked, methylmalonic acid used for FA instead of malonic acid= myelin destabilization. Need B12 for odd chain FA metabolism.
Homocystenuria
mental retardation,
eye lens dislocation,
bone elongation,
osteoprosis,
thrombosis!
Treat- mega dose of B6
Val, Ile & Leu
Defect in a ketoacid dehydrogenase branched chain
- maple syrup urine disease- caused by sotolone
- AR, severe mental def, optic atrophy, ataxia, fatigue, acidosis metabolic, ADHS, axial, hypotonia, hypoglycemia, exertional fatigue, high liver enz & aa branched in serum
- Death
Val & Ile Propionyl coA; Leu HMG- Co A
If propionyl co A converted to succinyl co A defect in methylmalonic aciduria
- FA & aa metabolism
Phe & Tyr
Phe converted to Tyr
PKU
- inherited rec defect in phenylalanine hydroxylase or dihydrobiopterine reductase (Phe to Tyr)
- seizures, spasticity, irreversible brain damage
- No Phe until adolescence!
- mandatory diaper test
- More common in UK than Japan
Dihyrobiopterine reductase defect
- problems w/ L DOPA production & 5 OH Trp.
- SE & catecholamine production issues.
Occulocutaneous albinism
syn of melanin & red hair pigment defective.
Get sun burnt very easily
Defects melanin (one of products of Tyr)
Vitiligo
Patchy, de pigmented skin .
Auto immune to melanocytes
Tyrosinemia
Tyrosinemia type I
- def in fumarylacetoacetate hydrolase (when tyr gets broken down to fumarate in series rxn)
- cabbage like urine smell
- Quebec
Type II
- tyrosine aminotransferase def
- damage brain, eyes & skin
Type III
- hydroxyphenyl pyruvate oxidase defect
- mild mental def & ataxia
- Hawkinsinuria- enz w/ reactive intermed. Produce hawkinsine.
- ADominant, acidemia only in 1st year of life (restrict phe & tyr)
- Hawkinsin= Cl- smell to urine.
Alkaptonuria
Benign, AR
Homogentisate oxidase def
Product excreted in urine, dark pigment when exposed to air.
Arthritis
Accumulates in tissues as ochronosis *related to tyr converted to fumarate pathway*
