week 2, lecture 3 Flashcards
vitamin B6 aka
pyridoxin - al, ine, amine
what type of reactions does b6 catalyze
transamination (amino acids into alpha ketoacids)
decarboxylation
trans and de sulfhydration
coenzyme of vitamin b6
PLP pyridoxal phosphate
how many vitamers of b6
6 forms of interchangeable vitamers
What needs to happen for the phosphorylated vitamers to be absorbed? What type of enzyme is used?
FOR B6
need to remove phosphate with phosphatase
What type of enzyme helps convert pyridoxal (PL) to the pyridoxal phosphate coenzyme form (PLP)? for b6
add phosphate group with a kinase
how does B6 help B3
B6 helps make the NAD+ coenzyme from the amino acid trytophan
NADH then go to ETC for energy
how does b6 help with glycogenolysis
- B6 helps glycogen phosphorylase release glucose
▪ Glucose can then be used for glycolysis → energy
NAD+ is converted to NADH by which of the energy producing pathways?
* A – glycolysis
* B – beta oxidation
* C – citric acid cycle
ALL OF THEM
how does B6 help with heme
- B6 helps condense succinyl CoA and glycine to the start heme synthesis pathway
what vitamins help make succinyl coa
b3, b2, b5
which neurotransmitters does B6 make
serotonin, dopamine, GABA
what reaction does B6 need to do to make neurotransmitters
decarboxylase enzyme
what does B6 make serotonin from
tryptophan
what does b6 make dopamine from
tyrosine
what does B6 make GABA from
glutamate
B6 turns tryptophan into
serotonin
B6 turns tyrosine into
dopamine
B6 turns glutamate into
GABA
how does B6 help gluconeogenesis (glucose from amino acids)
- Cys to pyruvate (FYI transamination and desulfhydration)
- Asp to oxaloacetate (transamination)
- Ala to pyruvate (transamination)
B6 and the glucose alanine cycle
helps with alanine-pyruvate transmutations to move from muscle to lvier
what does B6 do to linoliec acid
Desaturated fatty acid: turns it into Gamma-linolenic acid
which production of anti- inflammatory prostaglandins
how does B6 make cysteine from
- Made from homocysteine (HC)
and serine
▪ HC may be linked to increased risk of cardiovascular disease - Would B6 potentially increase or decrease this risk? decrease
B6 deficiencies
seizure (lack of GABA)
depression (lack of serotonin and dopamine)
microcytic anemia (RBC wrong size- heme synthesis)
inflammation (linoleic acid)
testing for B6 deficiency
tryptophan load test
what does the tryptophan load test test for
presence of xanthurenic acid in urine
if have b6 defiicney what are results in tryptophan land test
high xanthurenic acid
because tryptophan needs PLP to be converted into NAD and if PLP isn’t there it will just because xanthurenic acid instead
vitamin B7 aka
biotin
what reactions does biotin catalyze
redox
carboxylation
decarboxylation
what synthesis pathway uses b7
fatty acid synthesis
gluconeogeneis
what does the coenzyme form of B7 have
co2 and lysine
Coenzyme form of biotin has a CO2 attached and is linked to its enzyme by a lysine residue
how to absorb vitamin b7
- To absorb, need to remove the attached carboxylase enzyme via proteolysis
▪ Sometimes lysine is still attached
how does b7 help with gluconeogeneiss
convert pyruvate to oxaloacetate to then go into GNG
how does B7 help with fatty acid synthesis
acetyl coa –> malonyl coa
via acetyl coa carboxylate which needs a co2 from biotin/b7
how does biotin/b7 feed into heme synthesis and CAC
propionyl coa (from beta oxidation) uses co2 from biotin to make methylmalonyl coa to then make succinyl coa with will then feed into those 2 pathways
b7 helps make HMG CoA from what? then what can HMG coa make
start with leucine
use carboxylase enzyme
make HMG Coa to feed into cholesterol and ketone production
how does b7 increase glucokinase activity? What reaction does glucokinase catalyze? What happens to the product? What is the connection to blood sugar levels?
add phosphate to glucose to sequester in the cell, in the liver, lowers blood sugar
Convert pyruvate to oxaloacetate (carboxylation)
deficient in b7
No hallmark condition, but tend to see two types of symptoms:
▪ Neurological
* Ex: Lethargy, depression
▪ Dermatological
* Ex: Dermatitis (dry, red, scaly skin) and brittle nails
vitamin b9 aka
folate
folate aka
vitamin b9
biotin aka
b7
what function can folate do
methylation and 1 carbon transfer
what is the coenzyme form of b9
THF tetrahydrofolate
4 h’s
1 c group
multiple glutamates
how to absorb b9
remove glutamate and carbons via hydrolyses in the SI
how to metabolize B9
▪ B3 adds the H’s to create the THF form
* What do you think the enzyme name is? reductase
▪ Polyglu’s and a specific 1-C group are added
* Various B-vitamins interconvert folate coenzyme forms
b9/folate conversions
- NADPH helps reductase enzymes add H’s to make DHF, then THF
- 1-c groups are then added to the THF form
- note all B vitamins for folate conversion; b2, b3, b6, b12
- some THF forms help make purines and pyrimidine (DNA)
how if folate/b9 stored in the liver
stored in liver on folate binding proteins (FBP)
absorption of folate/b9
Absorption: Small intestine to gut to liver * Once in liver, could be:
▪ Converted to coenzyme forms and used by liver ▪Stored
▪ Sent to other tissues
▪ Cycled back to small intestine in the bile, another chance for absorption back to liver (enterohepatic circulation)
how to trap folate in liver or tissue
turn the monoglu into polyglu
aka in coenzyme form
monoglu for in blood stream
how does b9 make purines and pyrimidiens
- Required to support DNA replication
▪ Cells requiring a high rate of cell division are adversely impacted in a folate deficiency - Deficiency can lead to:
- Spina bifida, cancer
- Megaloblastic anemia
b9 deificneiy can lead to
- Spina bifida,
cancer - Megaloblastic anemia
depression
if you already have cancer should u take folate/ b9
no
but somehow can prevent some cancers
what does B9 help make methionine (amino acid) from
homocysteine
- The 1-C group (methyl) on methionine comes from
methyl folate. It is passed onto HC via methyl B12.
what is the purpose of making methionine ? products made?
make the methyl donor “SAM” (S-adenosyl-methionine)
Methyl is donated, products include:
- Choline
- Epinephrine
- Methylated DNA
What vitamin deficiency would cause a “methyl folate trap”?
What are the implications?
b12
A “methyl folate trap” occurs primarily due to a deficiency in vitamin B12 (cobalamin). In this scenario, folate (specifically in its active form, methyl folate) becomes trapped because vitamin B12 is necessary for the conversion of methyl folate to tetrahydrofolate, which is required for DNA synthesis and other metabolic processes.
could cause anemia, neurological…
what is the MTFHR gene? implications of poor activity?
It is made from methyleneTHF
(MTHF) via the MTHFR enzyme
Folate Metabolism: Individuals with MTHFR mutations may have impaired conversion of folate into its active form (L-methylfolate), potentially leading to deficiencies despite adequate dietary intake.
what levels of a coenzyme does folate correlate with (synthesiszes 2 neurotransmitters) that could lead to depression?
- Folate levels correlate with THB levels
▪ THB (FYI tetrahydrobiopterin) is a redox coenzyme that
helps with the synthesis of dopamine and serotonin - Indicates a possible role for folate deficiency in depression
vitamin b12 aka
cobalamin
Called “cobal”amin due to attached cobalt
cobalamin aka
vitamin b12
coenzyme forms of b12
methylcobalamin
adenosylcobalamin
what reaction does methylcobalamin coenzyme of b12 help with
▪Methioninesynthasereaction: transfersmethylgroup
from methyl folate to HC
- Makes methionine and regenerates THF
▪ Remember: deficiency leads to methyl folate trap
what is adenosylcobalamin coenzyme help form
formation of succinyl CoA from propionyl CoA
it goes propionyl coa –> methylmalonyl coa –> succinyl coa –> which can then feed into CAC and heme synthesis
what test for b12 deficiency
methylamalonic acid test—- cant convert propionyl coa into succinyl coa using the b12 adenosylcobalamin coenzyme
4 things need for b12 absorption
pepsin and hcl
r proteins
intrinsic factor
how does b12 get released from proteins in the stomach
pepsin and HCl in stomach
how does b12 get carried from the stomach into SI
Stomach: B12 carried by R-proteins
▪ Also found in saliva, continue to act in stomach
▪ Protect B12 from hydrolysis and bacterial use
how is b12 carried in the duodenum SI
- Duodenum: B12 released from R-protein and picked up by intrinsic factor (IF)
▪ IF made in stomach, acts in duodenum
▪ Carries B12 to a B12-IF receptor in ileum for absorption
where is b12 absorbed
ileum (distal SI)
what role do enterocytes play in b12 aborption
Enterocytes: Uptake of B12-IF-R via receptor-mediated endocytosis
▪ Receptor is recycled
▪ Vesicle fuses with lysosome
* IF is degraded
* B-12 is released
- B12 transported from enterocytes into blood
▪ Carried to tissues bound to transcobalamin II (TCII)
how is b12 taken up into tissues
Uptake via receptor mediated endocytosis
* Once in cell, chaperone proteins facilitate conversion to adenosyl- and methyl- cobalamin in the appropriate compartment
which compartments of the cell is adenosyl and methyl cobalamin in
adenosyl- mitochondria
methyl- cytosol
where is b12 stored and in what coenzyme form
- Mostly as adenosyl cobalamin
- Main site = liver, secondary = muscle
2 causes of b12 definceicy
- IF intrinsic factor deficiency
- hypochorhydria (HCL deficiency)
– symptoms are similar to B9 deficiency, including megalobastic anemia
A patient with megaloblastic anemia comes to see you. You suspect either a B12 or B9 deficiency, and you decide to try folate supplementation while waiting for lab results. Turns out you picked the wrong vitamin deficiency - the labs indicate a B12 deficiency. However, your B9 supplementation alone still ended up correcting the anemia. How?
b9 does purine and pyrimidine synthesis
methyl folate trap
B12 deficiency = methyl folate trap: can’t regenerate THF from methyl THF
Need THF to ultimately feed into purine and pyrimidine synthesis. Can provide THF as a supplement to circumvent lack of THF creation from B12.
what is an important deficiency symptom that B- 12 does NOT share with B9
is neurological deficits
Looks similar to Alzheimer’s
▪ Can take months/years to appear – why? bc b12 stored for long time
blood test for b12
▪ Blood test for B12
▪ Other options include blood tests for the following:
▪ Homocysteine
▪ Methylmalonic acid
would levels of homocysteine and methylmalonic acid be elevated or decreased in a B12 deficiency? Why?
increased
