Learning objectives: Nitrogen, amino acid derivatives Flashcards
Define the concept of nitrogen balance
- you want “amount of nitrogen coming in = amount of nitrogen going out”
- if positive nitrogen balance (more nitrogen coming in), maybe you’re a kid developing or a body builder (b/c nitrogen needed to make proteins)
- if negative nitrogen balance, you might be starving
Explain the role of protein degradation in normal nutrition and disease state
- in normal state, degrade some protein, but you’re still healthy
- in Marasmus (general starvation) or Kwashiorkor (just protein starvation), degrade way too much protein –> leads to ascites, edema, fatigue, loss of muscle/hair/teeth/skin pigment
Describe the metabolism of nitrogen - specifically the role of amino transferases
- aminotransferases move amino groups, usually need PLP (Vitamin B6 derivative)
- ALT (alanine transaminase) catalyzes the transfer of an amino group from alanine to alpha-ketoglutarate
- AST (aspartate transaminase) catalyzes the transfer of an amino group from aspartate to alpha-ketoglutarate
Describe the metabolism of nitrogen - specifically the role of ALT
- ALT (alanine transaminase) mostly in liver, used in alanine cycle, so nitrogen can be transported out
- catalyzes the transfer of an amino group from alanine to alpha-ketoglutarate
- rxn: alanine + alpha-ketoglutarate –> pyruvate + glutamate
- “TRANSaminase transfer amino group, the “mate/buddy” (glutamate) ends up with the nitrogen”
Describe the metabolism of nitrogen - specifically the role of AST
- AST (aspartate transaminase) used mostly in urea cycle
- catalyzes the transfer of an amino group from aspartate to alpha-ketoglutarate
- rxn: aspartate + alpha-ketoglutarate –> oxaloacetate + glutamate
- “TRANSaminase transfer amino group, the “mate/buddy” (glutamate) ends up with the nitrogen”
Describe the metabolism of nitrogen - specifically the role of glutamine synthetase
- catalyzes the condensation of glutamate and ammonia to form glutamine
- takes energy
- rxn: glutamate + ATP + NH3 –> glutamine + ADP + phosphate
- “synthesizes glutamine. glutamate is a buddy and gives up its nitrogen, glutaMINE is greedy and ends up w/ 2 nitrogens”
Describe the metabolism of nitrogen - specifically the role of glutaminase
- generates glutamate from glutamine
- doesn’t use ATP
- generates NH3 (ammonia) for urea synthesis
- rxn: glutamine + H2O –> Glutamate + NH3
- “glutaminase acts on glutamine, like an “ax” and takes away one of its nitrogens”
Describe the metabolism of nitrogen - specifically the role of glutamate dehydrogenase
- converts glutamate to alpha-ketoglutarate
- rxn: glutamate –> alpha-ketoglutarate + NH4+
- “dehydrogens glutamate, takes away NH2 from glutamate”
Discuss the diagnostic significance of aspartate aminotransferase and alanine amino transferase
- these enzymes are generally in the liver, to transfer amino groups from aspartate and alanine (respectively) and make glutamate
- this makes liver able to export nitrogen
- if these enzymes aren’t in the liver, there’s something wrong w/ liver, and you might have something like fatty liver disease
Describe the significance of the urea cycle in removing nitrogen
- urea cycle = how we get nitrogen out of the body
- 2 main enzymes in matrix: Carbamoyl phosphate synthetase I (CPS1), Ornithine Transcarbomylase (OTC)
- CPS1 starts w/ CO2, NH4+, ATP –> makes carbomyl phophate
- OTC brings carbomyl phophate + ornithine together –> makes citruline
- citruline can leave matrix, go to cytosol, eventually make urea
Describe the significance of the urea cycle in the presentation of hyperammonemia, with defects in urea cycle enzymes
- hyperammonemia = too much nitrogen
- likely due to defects in urea cycle enzymes, b/c then you can’t get enough urea out of your body
- ex: if you block the 2 main enzymes in urea cycle (CPS1 & OTC)
- can get compromised neurological function (tremors, slurred speech, drowsiness)
Describe the biosynthetic origin and basic function of histamine
made from histidine
function: stimulates mucus secretion, increases vascular permeability, allows white blood cells to go out and attack invaders, promotes gastric acid secretion
* if too much, can lead to asthma, allergic reaction
“hisssstamine, allergic rxn to a snake bite”
Describe the biosynthetic origin and basic function of gamma-aminobutryic acid (GABA)
made from glutamate (an excitatory neurotransmitter). need vitamin B6 to make GABA. GABA itself is an INHIBITORY neurotransmitter
function: inhibitory, so keeps things under control. if not enough GABA, get epileptic seizures
“if you don’t have GABA, you’ll go GAGA”
Describe the biosynthetic origin and basic function of nitric oxide (NO)
made from arginine
function: muscle relaxant (signals for cGMP –> decrease [Ca2+] –> muscle relaxes)
“nitric ooooxide, makes you go ooooooh and relax, for nooooo more stress. previously you’re like “arghhhh” cause you’re stressed, so you start w/ arginine”
Describe the biosynthetic origin and basic function of serotonin
made from tryptophan, using Vitamin B6 derivative (PLP)
neurotransmitter
changes in serotonin levels can lead to mood alteration
“sarahhhhh is needed to tone the mood down”
5 main molecules derived from tyrosine
thyroid hormone
melanin
catecholamines (dopamine, norepinephrine, epinephrine)
Describe the biosynthetic origin and basic function of thyroid hormone
made in thyroid from tyrosine
increases metabolic rate, growth & maturation, has organ-specific effects
“thighs are on ROIDS and grow bigger –> thyroid hormone related to growth”
Describe the biosynthetic origin and basic function of melanin
made from tyrosine using enzyme tyrosinase
proportion determines color of skin & hair
Describe the biosynthetic origin and basic function of catecholamines (dopamine, norepinephrine, epinephrine)
tyrosine –(catalyzed by tyrosine hydroxylase)–> Dopa –> dopamine –> norepinephrine –> epinephrine
too much dopamine –> schizophrenia
too little dopamine –> parkinson’s
Discuss the enzymatic defects in phenylketonuria (PKU)
phenylalinine –> tyrosine blocked
usually a defect in phenylalanine hydroxylase
Discuss the enzymatic defects in homocystinuria
cystathione synthase is blocked
can’t make cysteine
results in high levels of homocysteine–> homocysteine replaces cysteine in protein formation
disulfide bonds unable to form –> results in structural changes
Discuss the clinical consequences of phenylketonuria (PKU)
phenylalanine –> tyrosine blocked
results in tyrosine deficiency
can’t make as much melanin (light skin && hair), mental retardation - “think: puke (PKU) makes you pale”
Discuss the clinical consequences of homocystinuria
newborns seem healthy at first, but since disulfide bonds can’t form in proteins, later see structural deformities, vascular complications
