Amino Acid Metabolism part 1 Flashcards
(27 cards)
Sources of AA in AA pool
Dietary protein, Body protein, synthesis from essential AA
which source is in equilibrium with the AA pool
turnover of body proteins is in equilibrium with synthesis of AA into proteins
What is the AA pool used for in the body
synthesis of body protein, nitrogen free intermediates which turn into biosynthetic products, glucose and ketone bodies
What type of biosynthetic products are made from AA
neurotransmitters, creatine, purines, pyrimidines and porphyrins
What are the essential AA
PVT TIM HALL phenylalanine valine tryptophan threonine isoleucine methionine histidine *arginine (conditional) lycine leucine
How are proteins digested in the stomach?
Pepsinogen, made as an inactive precursor, is activated in stomach.
Pepsin partially cleaves dietary protein; pH of stomach 2-3 makes pepsin activity optimal
Dietary protein –> polypeptides and AA
How are polypeptides and AA digested in the intestine?
bicarbonate is released into the lumen, increasing pH. Pancreatic enzymes secreted into the lumen (Trypsin, chymotrypsin, elastase carboxypeptidase)
polypeptides and AA –> oligopeptides and AA
Then, intestinal mucosal cells secrete amino (di and tri) peptidases from amino terminus to carboxy terminus
oligopeptides –> free AA
How is nutrient digestion in the small intestine hormonally controlled?
Food in duodenal lumen (dietary lipids) stimulate release of two hormones into blood
CCK and Secretin- small polypeptide
Synthesized as larger precursors
CCK- decrease gastric mobility
Stimulates secretion of pancreatic enzymes
Stimulates gall bladder to secrete bile (emulsifies hydrophobic substances)
Secretin- stimulates pancreas to secrete bicarbonate
how many amino acid transporters exist? What are they used for?
7
used in uptake from the gut and reuptake into the kidney tubules
Which transporters are defective in cystinuria
“COAL”
cystine, ornithine, arginine, lysine
they appear in urine
cystine precipitates forming calculi (stones)
This is a recessive incidence 1:7000
What is Pellagra disorder?
deficiency of niacin (vitamin B3) which is involved in the synthesis of nicotine in nicotinamide adenine dinucleotide (NAD)
Rest of structure derived from metabolism tryptophan quinolinate intermediate
affects skin, GI tract and CNS
corn based diets can cause pellagra (low in trp and niacin)
What is Hartnup disorder?
deficiency of tryptophan - symptoms similar to pellagra
How is nitrogen balanced in a normal person?
body protein
I ^
V I
dietary protein-> AA pool –> urea, other stuff
When do you have a positive nitrogen balance?
growth, pregnancy due to increase in dietary protein and increase in body protein synthesis
When do you have a negative nitrogen balance?
protein deficiency due to lack of dietary protein and body protein synthesis
essential AA deficiency due to decrease of body protein synthesis and increase of AA -> urea/other conversions
wasting diseases burns and trauma due to increase of body protein conversion to AA and AA to urea/other conversion
What is kwashiorkor?
when infants are no longer breast fed and placed on starch rich diets - protein malnutrition
physical symptoms: failure to gain weight, stunted linear growth, generalized edema, swollen abdomen, diarrhea, skin depigmentation, reddish pigmentation of hair, and decreased muscle mass
mental changes: lethargy, apathy and irritability
physiological changes: fatty liver and anemia
final stages: shock, coma, death
treatment: gradually re-introduction of protein into diet
if not caught fast enough- irreversible damage
How do you remove nitrogen from amino acids?
there is an alpha amino group on ALL AA
removal by transamination
use transaminase AKA aminotransferase
(specific to one, or at most few, AA
transfer of amino group from AA to alpha-ketoglutarate
results in alpha keto acid and glutarate respectively
reversible rxn; glutamate universal acceptor of amino groups for almost all AAs
What are the two most important aminotransferase reactions catalyzed by?
Alanine aminotransferase ALT
transfer amino group from alanine to alpha-ketoglutarate-> pyruvate (and glutamate)
aspartate aminotransferase AST
AST is an exception to the rule that aminotransferases funnel amino groups to form glutamate.
transfers amino groups from glutamate to oxaloacetate-> aspartate (and alphaketoglutarate) which is used as a source of nitrogen in the urea cycle
both require coenzyme PLP
pyridoxal phosphate
What aminotransferase levels are high during liver disease?
Plasma AST (6-40 IU/L) and ALT (10-40 IU/L) are elevated in nearly all liver diseases
What is the mechanism of transamination reactions?
cyclic interconversion of pyridoxal phosphate to pyridoxamine phosphate
ex: AST transfer of amino group from glutamate to PLP
PLP -> pyridoxamine phosphate
which is then transferred to OOA resulting in aspartate
pyridoxamine phosphate-> back to PLP
Following ingestion of the toxic mushroom amanita phalloides, which enzyme is released in the plasma?
Plasma AST and ALT are elevated in nearly all liver diseases, but are particularly high in conditions that cause extensive cell necrosis, such as severe viral hepatitis, toxic injury, and prolonged circulatory collapse.
ALT is more specific for liver disease.
released early, before bilirubin.
How is glutamate deaminated?
oxidative deamination via
glutamate dehydrogenase
Use NAD+ –> NADH and release of NH3
resulting in alphaketoglutarate
reverse the reaction using the same enzyme BUT with NADPH -> NAD and addition of NH3
when ammonia levels are high in the blood, the second reaction is preferred; glutamate sucks up all the ammonia
How do the reactions couple during disposal of AA and synthesis of AA?
disposal: transamination (glutamate universal acceptor of amine groups for almost ALL AA) followed by oxidative deamination
synthesis: reductive amination followed by transamination to form AA
What are the allosteric modulators of glutamate dehydrogenase?
GTP inhibits
ADP activates
energy low- get energy from carbon skeleton of AA
