B6 (mine)

what are the forms of B6 (6)

Pyrixidone (PN)

Pyridoxal (PL)

Pyridoxamine (PM)

Pyridoxine phosphate (PNP)

Pyridoxal phosphate (PLP)

pyridoxamine phosphate (PMP)

what is the stable form of B6?

pyridoxine

where is pyridoxine mainly found?

primarily found in plants

what other forms can be found in plants?

smaller amounts found of the other 2 forms (pyridoxal and pyridoxamine), as well as phosphorylated form 

Animal sources consist of what form(s) of B6?

pyridoxal phosphate (PLP) & pyridoxamine phosphate (PMP)

what is main functional form in the body?

pyridoxal (PL) and pyridoxal phosphate (PLP)

Some _____ forms found in plants are less ____

glucoside

bioavailable

what is a major issue with B6

bioavailability due to processing

alcohol form of B6

Pyridoxine

aldehyde form

pyridoxal

amine form

Pyridoxamine

prior to absorption, what must occur 

phosphorylated forms must be dephosphorylates 

How are phosphorylated forms dephosphorylated?

by alkaline phosphatase (zn dependent)

alkaline phosphatase is dependent on what?

Zinc

absorption occurs in ___ via ___

jejunum via passive diffusion

absorption rates

61-92%

within intestinal cells, what can occur

some pyridoxine can be phosphorylated

Most PN, PL & PM are released to ____

portal blood

what occurs in the liver to B6 that allows for function?

forms are converted into PLP (interconversion)

where does interconversion of B6 forms occur? 

liver (SUPER IMPORTANT)

PN become what, how?

PNP through kinase (ATP)

PM becomes what, how?

PMP through kinase (ATP)

kinase is _____ dependent

ATP

PMP/PNP can become what?

PLP

in order for PMP/PNP to become PLP, what is needed?

oxidase (PMP or PNP oxidase)—> FMN dependent 

LACKING IN MANY OTHER TISSUES

PMP & PNP oxidase is dependent on

FMN (riboflavin)

in order for PLP, PMP, and PNP to be converted back into unphosphorylated form, what is needed?

phosphatase enzyme

what is the main form of B6 in blood? 

pyridoxal phosphate (PLP) —> 60-90%

what can happen to PL in RBC

phosphorylated into PLP and bound to hemoglobin

must PL be phosphorylated?

no, it may stay as PL

In RBC, PL binds to ___ of ____ & PLP bind to ____

PL binds to alpha chain of hemoglobin

PLP binds to beta chain of hemoglobin

In plasma, PLP & PL are bound to ____

albumin (small amounts of PM also binds)

before it PLP can be uptake into other tissues, what must occur to it?

hydrolyzed by alkaline phosphatase

conversion of Pyridoxamine or pyridoxamine phosphate -> Pyridoxal phosphate uses what

FMN-dependent oxidase

liver stores how much of B6?

5-10% (NOT MAJOR STORAGE, but major for metabolism)

what occurs to all 3 forms of B6 in the liver?

they are phosphorylated

where is PLP mostly stored?

muscle (75-80%)

PLP in the muscle is bound to

glycogen phosphorylase

glycogen phosphorylase is an enzyme associated w/ ...

glycogen utilization (breakdown of glycogen into glucose uses PLP; PLP adds the phosphate to glucose to form G6P and make it useful)

can most tissues form PLP?

NO..

what cant most tissues make PLP?

they lack PMP/PNP oxidase enzymes (FMN dependent) needed to convert PN/PM into PLP

what tissues can the coenzyme form also be found in

brain

kidneys

spleen

Functions of B6 (9 general)

100+ reactions

• decarboxylation of AA (decarboxylase)

• transamination (transaminase)

• Transelenation (selenium)

• rearrangement of Amino Acids (D- & L- AA)

• Heme synthesis

• CHO metabolism

•Lipid metabolism

• Neurotransmitter synthesis

• Conversion of tryptophan -> niacin

Transamination Rx uses what forms of B6 as coenzyme?

PMP & PLP

Transamination Rx is related to what enzyme

transaminase

what are the main 2 aminotransferase enzymes?

• aspartate aminotransferase (AST) also known as glutamate oxaloacetate (GOT)

• Alanine aminotransferase (ALT) also known as glutamate pyruvate tranaminase (GPT)

Transamination Rx: important for formation of what

Schiff base compounds (Carbon Nitrogen double bonds)

how does PLP/PMP work in transamination of AA

PLP will bind to enzyme --> Amino acid will bind to PLP (forming schiff base compounds) --> then whole structure becomes ketimine when it rearrange samino acid to become keto acid--> then release keto acid

 

PMP will bind to enzyme --> keto acid will bind to PMP becoming ketimine--> then will become aldimine when rearranges keto acid to become amino acid-->  then PMP will release amino acid

cysteine is made from what starting compound?

methionine

what is needed for cystein synthesis?

PLP for transsulfyhydration

___ is synthesized from methionine via ___ (what reaction)

cysteine; transsulfyhydration

cysteine can eventually lead to the synthesis of what compound

pyruvate

Cysteine undergoes ____ followed by ___ to generate pyruvate

dehydration , transamination

Transelenation involves conversion of ___ to ____

selenomethionine to selenocysteine

how does cysteine metabolism begin? (what compound)

with methionine

methionine is converted into what?

homocysteine 

homocysteine -> is converted into what (enzyme?)

cystathione via Cystathione synthase (PLP)

what enzyme is used to convert homocysteine into cystathione?

cystathionine synthase

cystathionine synthase depends on

PLP

Cystathione is converted into what? enzyme?

Cysteine via cystathione lyase (PLP)

conversion of cystathionine to cysteine uses what enzyme?

cystathionine lyase

cystathionine lyase depends on

PLP

Cysteine can convert to?

Taurine (no PLP needed)

B6 role with neurotransmitter?

involved in decarboxylation 

in which reactions is B6 involved regarding neurotransmitter decarboxylation?

Glutamate —> GABA (via glutamate decarboxylase)

Tryptophan —> serotonin (decarboxylation reaction)

Glutamate -> GABA uses what

Glutamate decarboxylase (B6)

homocysteine (from methionine metabolism) produces what? (effect) 

toxic effect on arterial wall (atherosclerosis) 

S-hydroxytryptophan -> S-hydroxytryptamine (serotonin) uses what

Aromatic AA & Decarboxylase (PLP)

homocysteine is metabolized by what vitamins?

B6, B12, Folate

regarding heme synthesis, what form of B6 is needed?

PLP

how is PLP involved in heme synthesis

required for amino-levulinic acid synthase (uses glycine and succinyl CoA to synthesize delta-aminolevulinic acid (ALA))

What does amino-levulinic acid synthase do?

uses glycine and succinyl CoA to synthesize delta-aminolevulinic acid (ALA)

ALA is used to synthesize ___

porphobilinogen

porphobilinogen is a precursor for?

porphyrin synthesis which will results in formation of heme

other functions of B6? (5)

• Formation of niacin from tryptophan also requires PLP as a cofactor for a rate limiting enzyme

• Involved in formation of histamine from histadine

• Synthesis of dopamine from taurine

• Steroid receptor binding activity is modulated by presence of B6

• serine synthesis and metabolism (shown in folic acid lecture)

B6 and niacin?

Formation of niacin from tryptophan requires PLP as a cofactor in rate limiting enzyme (kynureninase)

B6 is involved in formation of ___ from histidine

histamine

what enzyme is needed to form histamine from histidine (dependent on?)

histidine decarboxylase (PLP)

B6 is involved in the synthesis of ___ from taurine

dopamine

What is modulated by B6

steroid receptor binding

what covered in folate lecture uses B6 (for its synthesis and metabolism)

serine

glycogen degradation and B6?

PLP is needed for glycogen phosphorylase activity

Glycogen degradation: ___ from PLP bind to form ____

phosphate

glucose-1-phosphate

major metabolite of B6?

4-pyridoxic from PL oxidation

4-pyridoxic is excreted how?

excreted via urine

4-pyridoxic excretion is indicative of

intake levels

Large doses of PN can result in....

intact urinary losses & 5-& 4- pyridoxic acid

excretion via feces

little or no excretion

RDA for men & women

Men 19-50: 1.3mg

men 51<: 1.7mg

women: 19-50: 1.3mg

women 51<: 1.5mg

RDA for prg & lact & daily value

pregnancy: 1.9mg

lactation: 2.0mg

DV: 2mg

Deficiency of B6 can result in (5)

• Microcytic hypochromic anemia

• Seborrheic dermatitis

• Convulsion, depression, confusion

• Reduced immune response

• Peripheral nerve damage

Toxicity of B6 (causes what?)

• Sensory & peripheral neuropathy

• UL = 100 mg

Alcohol effects formation of what

PLP formation

L-DOPA-medication used to treat Parkinson's disease and anti-tuberculosis medication isoniazids affects of PLP

-Reduce blood concentration of PLP

-require supplementation of B-6

assessment of adequacy for B6? (6)

Tryptophan loading test

xanthurenic excretion

Plasma PLP concentrations

urinary B6 & 4-pyridoxic

enterocyte transaminase activity (before & after)

transaminase enzymes (w/ B6 bolus)