week 2, lecture 3 Flashcards

1
Q

vitamin B6 aka

A

pyridoxin - al, ine, amine

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2
Q

what type of reactions does b6 catalyze

A

transamination (amino acids into alpha ketoacids)

decarboxylation

trans and de sulfhydration

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3
Q

coenzyme of vitamin b6

A

PLP pyridoxal phosphate

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4
Q

how many vitamers of b6

A

6 forms of interchangeable vitamers

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5
Q

What needs to happen for the phosphorylated vitamers to be absorbed? What type of enzyme is used?
FOR B6

A

need to remove phosphate with phosphatase

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6
Q

What type of enzyme helps convert pyridoxal (PL) to the pyridoxal phosphate coenzyme form (PLP)? for b6

A

add phosphate group with a kinase

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7
Q

how does B6 help B3

A

B6 helps make the NAD+ coenzyme from the amino acid trytophan

NADH then go to ETC for energy

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8
Q

how does b6 help with glycogenolysis

A
  • B6 helps glycogen phosphorylase release glucose
    ▪ Glucose can then be used for glycolysis → energy
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9
Q

NAD+ is converted to NADH by which of the energy producing pathways?
* A – glycolysis
* B – beta oxidation
* C – citric acid cycle

A

ALL OF THEM

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10
Q

how does B6 help with heme

A
  • B6 helps condense succinyl CoA and glycine to the start heme synthesis pathway
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11
Q

what vitamins help make succinyl coa

A

b3, b2, b5

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12
Q

which neurotransmitters does B6 make

A

serotonin, dopamine, GABA

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13
Q

what reaction does B6 need to do to make neurotransmitters

A

decarboxylase enzyme

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14
Q

what does B6 make serotonin from

A

tryptophan

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15
Q

what does b6 make dopamine from

A

tyrosine

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16
Q

what does B6 make GABA from

A

glutamate

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17
Q

B6 turns tryptophan into

A

serotonin

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18
Q

B6 turns tyrosine into

A

dopamine

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19
Q

B6 turns glutamate into

A

GABA

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20
Q

how does B6 help gluconeogenesis (glucose from amino acids)

A
  • Cys to pyruvate (FYI transamination and desulfhydration)
  • Asp to oxaloacetate (transamination)
  • Ala to pyruvate (transamination)
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21
Q

B6 and the glucose alanine cycle

A

helps with alanine-pyruvate transmutations to move from muscle to lvier

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22
Q

what does B6 do to linoliec acid

A

Desaturated fatty acid: turns it into Gamma-linolenic acid

which production of anti- inflammatory prostaglandins

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23
Q

how does B6 make cysteine from

A
  • 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
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24
Q

B6 deficiencies

A

seizure (lack of GABA)
depression (lack of serotonin and dopamine)
microcytic anemia (RBC wrong size- heme synthesis)
inflammation (linoleic acid)

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25
Q

testing for B6 deficiency

A

tryptophan load test

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26
Q

what does the tryptophan load test test for

A

presence of xanthurenic acid in urine

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27
Q

if have b6 defiicney what are results in tryptophan land test

A

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

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28
Q

vitamin B7 aka

A

biotin

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29
Q

what reactions does biotin catalyze

A

redox
carboxylation
decarboxylation

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30
Q

what synthesis pathway uses b7

A

fatty acid synthesis
gluconeogeneis

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31
Q

what does the coenzyme form of B7 have

A

co2 and lysine

Coenzyme form of biotin has a CO2 attached and is linked to its enzyme by a lysine residue

32
Q

how to absorb vitamin b7

A
  • To absorb, need to remove the attached carboxylase enzyme via proteolysis
    ▪ Sometimes lysine is still attached
33
Q

how does b7 help with gluconeogeneiss

A

convert pyruvate to oxaloacetate to then go into GNG

34
Q

how does B7 help with fatty acid synthesis

A

acetyl coa –> malonyl coa

via acetyl coa carboxylate which needs a co2 from biotin/b7

35
Q

how does biotin/b7 feed into heme synthesis and CAC

A

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

36
Q

b7 helps make HMG CoA from what? then what can HMG coa make

A

start with leucine

use carboxylase enzyme

make HMG Coa to feed into cholesterol and ketone production

37
Q

how does b7 increase glucokinase activity? What reaction does glucokinase catalyze? What happens to the product? What is the connection to blood sugar levels?

A

add phosphate to glucose to sequester in the cell, in the liver, lowers blood sugar

Convert pyruvate to oxaloacetate (carboxylation)

38
Q

deficient in b7

A

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

39
Q

vitamin b9 aka

A

folate

40
Q

folate aka

A

vitamin b9

41
Q

biotin aka

A

b7

42
Q

what function can folate do

A

methylation and 1 carbon transfer

43
Q

what is the coenzyme form of b9

A

THF tetrahydrofolate

4 h’s
1 c group
multiple glutamates

44
Q

how to absorb b9

A

remove glutamate and carbons via hydrolyses in the SI

45
Q

how to metabolize B9

A

▪ 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

46
Q

b9/folate conversions

A
  1. NADPH helps reductase enzymes add H’s to make DHF, then THF
  2. 1-c groups are then added to the THF form
  3. note all B vitamins for folate conversion; b2, b3, b6, b12
  4. some THF forms help make purines and pyrimidine (DNA)
47
Q

how if folate/b9 stored in the liver

A

stored in liver on folate binding proteins (FBP)

48
Q

absorption of folate/b9

A

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)

49
Q

how to trap folate in liver or tissue

A

turn the monoglu into polyglu

aka in coenzyme form

monoglu for in blood stream

50
Q

how does b9 make purines and pyrimidiens

A
  • 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
51
Q

b9 deificneiy can lead to

A
  • Spina bifida,
    cancer
  • Megaloblastic anemia
    depression
52
Q

if you already have cancer should u take folate/ b9

A

no

but somehow can prevent some cancers

53
Q

what does B9 help make methionine (amino acid) from

A

homocysteine

  • The 1-C group (methyl) on methionine comes from
    methyl folate. It is passed onto HC via methyl B12.
54
Q

what is the purpose of making methionine ? products made?

A

make the methyl donor “SAM” (S-adenosyl-methionine)

Methyl is donated, products include:
- Choline
- Epinephrine
- Methylated DNA

55
Q

What vitamin deficiency would cause a “methyl folate trap”?
What are the implications?

A

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…

56
Q

what is the MTFHR gene? implications of poor activity?

A

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.

57
Q

what levels of a coenzyme does folate correlate with (synthesiszes 2 neurotransmitters) that could lead to depression?

A
  • 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
58
Q

vitamin b12 aka

A

cobalamin

Called “cobal”amin due to attached cobalt

59
Q

cobalamin aka

A

vitamin b12

60
Q

coenzyme forms of b12

A

methylcobalamin

adenosylcobalamin

61
Q

what reaction does methylcobalamin coenzyme of b12 help with

A

▪Methioninesynthasereaction: transfersmethylgroup
from methyl folate to HC

  • Makes methionine and regenerates THF

▪ Remember: deficiency leads to methyl folate trap

62
Q

what is adenosylcobalamin coenzyme help form

A

formation of succinyl CoA from propionyl CoA

it goes propionyl coa –> methylmalonyl coa –> succinyl coa –> which can then feed into CAC and heme synthesis

63
Q

what test for b12 deficiency

A

methylamalonic acid test—- cant convert propionyl coa into succinyl coa using the b12 adenosylcobalamin coenzyme

64
Q

4 things need for b12 absorption

A

pepsin and hcl
r proteins
intrinsic factor

65
Q

how does b12 get released from proteins in the stomach

A

pepsin and HCl in stomach

66
Q

how does b12 get carried from the stomach into SI

A

Stomach: B12 carried by R-proteins

▪ Also found in saliva, continue to act in stomach
▪ Protect B12 from hydrolysis and bacterial use

67
Q

how is b12 carried in the duodenum SI

A
  • 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
68
Q

where is b12 absorbed

A

ileum (distal SI)

69
Q

what role do enterocytes play in b12 aborption

A

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)
70
Q

how is b12 taken up into tissues

A

Uptake via receptor mediated endocytosis
* Once in cell, chaperone proteins facilitate conversion to adenosyl- and methyl- cobalamin in the appropriate compartment

71
Q

which compartments of the cell is adenosyl and methyl cobalamin in

A

adenosyl- mitochondria
methyl- cytosol

72
Q

where is b12 stored and in what coenzyme form

A
  • Mostly as adenosyl cobalamin
  • Main site = liver, secondary = muscle
73
Q

2 causes of b12 definceicy

A
  1. IF intrinsic factor deficiency
  2. hypochorhydria (HCL deficiency)
    – symptoms are similar to B9 deficiency, including megalobastic anemia
74
Q

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?

A

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.

75
Q

what is an important deficiency symptom that B- 12 does NOT share with B9

A

is neurological deficits

Looks similar to Alzheimer’s
▪ Can take months/years to appear – why? bc b12 stored for long time

76
Q

blood test for b12

A

▪ Blood test for B12
▪ Other options include blood tests for the following:
▪ Homocysteine
▪ Methylmalonic acid

77
Q

would levels of homocysteine and methylmalonic acid be elevated or decreased in a B12 deficiency? Why?

A

increased