Amino Acid Metabolism part 1

Question 1

Sources of AA in AA pool

Answer 1

Dietary protein, Body protein, synthesis from essential AA

Question 2

which source is in equilibrium with the AA pool

Answer 2

turnover of body proteins is in equilibrium with synthesis of AA into proteins

Question 3

What is the AA pool used for in the body

Answer 3

synthesis of body protein, nitrogen free intermediates which turn into biosynthetic products, glucose and ketone bodies

Question 4

What type of biosynthetic products are made from AA

Answer 4

neurotransmitters, creatine, purines, pyrimidines and porphyrins

Question 5

What are the essential AA

Answer 5

PVT TIM HALL
phenylalanine
valine
tryptophan
threonine
isoleucine
methionine
histidine
*arginine (conditional)
lycine
leucine

Question 6

How are proteins digested in the stomach?

Answer 6

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

Question 7

How are polypeptides and AA digested in the intestine?

Answer 7

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

Question 8

How is nutrient digestion in the small intestine hormonally controlled?

Answer 8

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

Question 9

how many amino acid transporters exist? What are they used for?

Answer 9

7

used in uptake from the gut and reuptake into the kidney tubules

Question 10

Which transporters are defective in cystinuria

Answer 10

“COAL”
cystine, ornithine, arginine, lysine
they appear in urine

cystine precipitates forming calculi (stones)

This is a recessive incidence 1:7000

Question 11

What is Pellagra disorder?

Answer 11

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)

Question 12

What is Hartnup disorder?

Answer 12

deficiency of tryptophan - symptoms similar to pellagra

Question 13

How is nitrogen balanced in a normal person?

Answer 13

body protein
I ^
V I
dietary protein-> AA pool –> urea, other stuff

Question 14

When do you have a positive nitrogen balance?

Answer 14

growth, pregnancy due to increase in dietary protein and increase in body protein synthesis

Question 15

When do you have a negative nitrogen balance?

Answer 15

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

Question 16

What is kwashiorkor?

Answer 16

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

Question 17

How do you remove nitrogen from amino acids?

Answer 17

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

Question 18

What are the two most important aminotransferase reactions catalyzed by?

Answer 18

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

Question 19

What aminotransferase levels are high during liver disease?

Answer 19

Plasma AST (6-40 IU/L) and ALT (10-40 IU/L) are elevated in nearly all liver diseases

Question 20

What is the mechanism of transamination reactions?

Answer 20

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

Question 21

Following ingestion of the toxic mushroom amanita phalloides, which enzyme is released in the plasma?

Answer 21

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.

Question 22

How is glutamate deaminated?

Answer 22

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

Question 23

How do the reactions couple during disposal of AA and synthesis of AA?

Answer 23

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

Question 24

What are the allosteric modulators of glutamate dehydrogenase?

Answer 24

GTP inhibits
ADP activates

energy low- get energy from carbon skeleton of AA

Question 25

What is D serine and what does it do?

Answer 25

present in diet and made from L-serine via serine racemase.
It modulates NDMA-type glutamate receptors
it’s also involved in synaptic plasticity and development

Question 26

What is DAO

Answer 26

D-Amino acid oxidase (DAO) is an FAD-depen- dent peroxisomal enzyme that catalyzes the oxidative deamination of D-amino acids producing α-keto acids, ammonia, and hydrogen peroxide.
increased DAO activity linked to schizophrenia

Question 27

How is ammonia transferred from the muscle to the liver?

Answer 27

TWO ways:
GLUTAMINE:
glutamate can react with free AAs and form glutamine via glutamine synthetase and ATP
glutamine has an alpha amino group and amide linkage at the gamma position; it is a non toxic form of ammonia and can be transported in the blood safely
In the liver it is deaminated back to glutamate via glutaminase and H2O, the free ammonia enters the urea cycle

ALANINE:
glutamate can react with free AAs
glutamate and pyruvate (ALT) -> alpha ketoglutarate and alanine, respectively
Alanine another non toxic transport form of amino group
Reform pyruvate in liver via ALT rxn
Glutamate acceptor of NH3
Glutamate dehydrogenase
free ammonia enters ureal cycle

pyruvate can be used in gluconeogenesis -> glucose which can be released from the liver