AA Metabolism Flashcards
what is a positive nitrogen balance?
nitrogen intake exceeds excretion
who would have a positive nitrogen balance?
babies, burn victims trying to repair, people who are growing
what is negative nitrogen balance?
nitrogen excretion exceeds intake, see this in essential amino acid deficiency
how many AA cannot be synthesized by the human body, and what happens if they are not taken in by the diet?
9 AA are essential, meaning they cannot be synthesized by the body. if don’t have all 20 AA or if it can’t be done quick enough, cannot do protein biosynthesis, and we excrete more N than normal.
what does glucogenic/glycogenic AA mean?
some amino acids ONLY go on to make pyruvate or intermediates of the TCA cycle, that can go on to make glucose in the liver
what does ketogenic AA mean??
some amino acids ONLY go on to make acetyl coa or ketone bodies
what amino acid is ONLY ketogenic?
leucine
what is special in the proximal convoluted tubules regarding AA transport?
the special AA transporter that is in the intestinal epithelium is also in the proximal tubules in the kidney. it is used to reabsorb cystine, homocystine, lysine, ornithine, or arginine.
what is cystine?
cysteine hooked together with sulfhydryl cross link - is not very soluble in urine, so you want to reabsorb it to the blood to prevent kidney stones
what happens in cystinuria?
if the special cystine transporter in the PCT is not working, it cannot reabsorb cystine, homocystine, lysine, arginine, or ornithine into the blood, therefore, increased kidney stones.
diagnosis of cystinuria?
take urine and assay of kidney stone for lysine, arginine, ornithine in higher concentrations than normal.
how are branched chain amino acids taken up into the cells?
- in the muscle, they must be transaminated to their alpha keto acids (are branched alpha keto acids) because they are insoluble. 2. they are transported as their alpha keto acids to the liver. 3. liver oxidatively decarboxylates them by oxidative decarboxylation dehydrogenase (alpha ketoacid dehydrogenase) 4. then can undergo further degradation and handling to their respective gluconeogenic or ketogenic worlds
what enzyme is in the liver that decarboxylates alpha keto acids derived from branched chain AA?
oxidative decarboxylation dehydrogenase/alpha ketoacid dehydrogenase
what occurs if alpha ketoacid dehydrogenase is deficient?
problem in the liver - branched chain alpha keto acids accumulate in the blood and urine - maple syrup urine disease - AA don’t accumulate in the blood, bc muscle has transaminated them to their branched chain alpha ketoacids
symptoms of maple syrup urine disease
1.maple syrup odor of urine 2. mental retardation (bc branched chain alpha ketoacids cross BBB) 3. abnormal muscle tone 4. ketosis (bc branched chain alpha ketoacids) 5. coma 6. death
describe phenylalanine and tyrosine metabolism
- phenylalanine —> tyrosine via phenylalanine hydroxylase/BH4 2. later in the pathway, homogentisate —->—>fumarate and acetoacetate via homogentisate oxidase
where does phenylalanine breakdown occur?
in stomach via phenylalanine hydroxylase, which requires tetrahydrobiopterin (BH4)
pathology of phenylketonuria (PKU)
- phenylalanine hydroxylase is deficient, so phenylalanine is not converted to tyrosine 2. phenylalanine builds up and leads to transamination into phenylpyruvate 3. phenylpyruvate spontaneously loses CO2 and becomes phenylacetate, or is reduced to phenyllactate 4. phenylacetate and phenyllactate build up in the blood, leading to phenylketonuria
symptoms of PKU
- mental retardation 2. microcephaly 3. musty odor
treatment of PKU
- diet low in Phe 2. avoid aspartame (is a tripeptide with Phe in it, so when degraded, becomes Phe) 3. have a good diet during pregnancy
what is alkaptonuria?
part of phe and tyrosine metabolism: homogentisate oxidase is deficient, so homogentisate cannot go to fumarate or acetoacetate. homogentisic acid builds up.
what is the triad of alkaptonuria?
- dark urine - see in childhood 2. ochronosis - see later in life (homogentisate builds up in joints) 3. arthritis - see later in life (homogentisate builds up in joints)
what is the propionic acid pathway of vomit?
Valine or Methionine Isoleucine Threonine
describe normal metabolism of methionine
- S-adenosyl methionine (SAM) pulls off a methyl from methionine to become S-adenosylhomocysteine
- SAH becomes homocysteine
- homocysteine becomes cystathionine via cystathionine synthase and PLP/B6
- cystathionine becomes alpha ketobutyrate and cysteine via cystathionine lyase and PLP/B6
- alpha ketoglutarate becomes propionyl CoA
- propionyl CoA becomes D-methylmalonyl CoA via biotin
- D-methylmalonyl CoA becomes L-methylmalonyl CoA
- L-methylmalonyl CoA becomes succinyl CoA via B12
- succinyl CoA goes to TCA cycle
