nitrogen sources and disposal Flashcards
breakdown of dietary proteins? Where and how?
in stomach, digested in di- and tripeptidase by proteinases
peptidases on the surface of intestinal cells (in the brush boarder) then break these down into amino acids
absorption of amino acids depends on?
depends on active transport by sodium symport systems in plasma membrane of intestinal cells
essential AA are? Where do we get them?
9: phe, met, trp, lys, thr, his, leu, ile, val
protein from different foods are equally effective as a source of energy and nitrogen but nutritional value varies based on AA composition - low content of one or more of the essential AA increases the amount of that protein required to maintain the nitrogen balance
protein turnover pathways between meals?
between meals or in protein-free diet degrade cellular protein
by ubiquitin-proteaosome pathway or lysosome degradation pathway
ubiquitin proteasome pathway
depends on covalent attachment of ubiquitin to lysine residues of protein targeted for degradation
polyubiquinated protein then recognized by proteasome complex and degraded in ATP dependent process
responsible for degradation of targeted proteins
insulin (via IRS1 receptor) inhibits this process
lysosome degradation pathway
responsible for degradation of bulk cellular proteins and organelles
cytosolic material sequestered into membrane bound compartment - autophagy
autophagosomes fuse with lysosomes/vacuoles where proteases and lipases can degrade the contents
high insulin levels after meals inhibit process, starvation stimulates process
regulation of protein synthesis
regulated at ribosomal level
under starvation: initiation factor eIF2 is sequestered and/or phosphorylated to inhibit it
insulin and increased AA levels result in phosphorylation of 4E-BP1 - triggers release of eIF4
amino acid catabolism
Routes?
free AA from AA pools catabolized to lipogenic and gluconeogenic precursors depending on metabolic status
two routes:
aminotransferase reactions
oxidative deaminiation
aminotransferase reactions
reversible
aka transaminases
specific enzyme for each AA and keto-acid pair
most occur in liver, also in muscle during starvation
transamination usually last step in synthesis of AA and first in degradation
require pyridoxal phosphate (PLP; derivative of vitamin B6)
common examples:
alanine aminotransferase:
alanine + alpha-ketoglutamate => pyruvate + glutamate
aspartate aminotransferase:
aspartate + alpha-ketoglutamage => oxaloacetate + glutamate
catabolism can create excess amino groups which can be funneled to glutamate by conversion of alpha-keto glut to glutamate - allows these to be used for metabolism
step in aminotransferase reaction
need pyridoxal phosphate (PLP) at active site
catalytic mechanism transfers the amino group of an amino acid to the coenzyme => pyridoxamine phosphate intermediate
hydrolysis releases an alpha-keto acid
intermediate reacts with another alpha-keto acid to form an amino acid (often glutamate) and regenerates the bound PLP
equilibrium constant for most aminotransferases near one so reaction controlled by substrate concentration
AA that can make alpha-ketoglutarate
arginine, glutamate, glutamine, histidine, proline
AA that can make succinyl coA
isoleucine
methionine
threonine
valine
AA that can make fumarate
aspartate
phenylalanine
tyrosine
AA that can make oxaloacetate
asparagine
aspartate
AA that can make pyruvate
alanine cysteine glycine serine threonine tryptophan
AA that can make acetyl CoA
isoleucine
leucine
tryptophan
AA that can make acetoacetyl CoA
leucine lysine phenylalanine tryptophan tyrosine
glutamate dehydrogenase
oxidative deamination reaction in mammals
converts glutamate to alpha-ketoglutarate (aKG) and ammonia
reversible
direction depends on concentrations of glutamate, ammonia, and aKG
abundant in liver, localizes to mitochondrial matrix
hepatic urea cycle (general - why? Where?)
NH4 toxic so must be converted to urea
urea transported to kidney via circulatory system and excreted in urine
(more details in next lecture)
alkaptonuria
deficiency in homogentisate oxidase - enzyme in pathway for degradation of tyrosine
homogentisate accumulates and is excreted in urine
produces dark pigments upon oxidation - visible in urine but also build up in joints, causing arthritis
maple syrup urine disease (MSUD)
due to deficiency in branched-chain alpha-keto acid dehydrogenase
results in accumulation of leucine, isoleucine and valine
causes neurological deficits, odor of maple syrup in urine, high mortality rate
treat with dietary restriction of branched AA
homocystinuria
most commonly due to deficiency in enzyme cystathionine beta-synthase - converts homocystein to cystathionine
in pathway for catabolism of methionine
causes osteoporosis, mental retardation, and potentially increase in risk of cardiac disease
can also be caused by deficiencies in folic acid
phenylketonuria (PKU)
deficiency in phenylalanine metabolism - results in neurological deficits - discussed further in later lecture
