Vitamin B6 (5 questions)

Question 1

What are the CoE. forms of B6?

Answer 1

1) PNP: Pyridoxine phosphate

2) PLP: Pyridoxal phosphate

3) PMP: Pyridoxamine phosphate

Question 2

What CoE. forms are provided by animal products?

Answer 2

PL, PLP, PM, and PMP

Question 3

What CoE. forms are provided by plant products?

Answer 3

PN, PNP. Often conjugated with glucoside which reduces the B6 bioavailability to 50%

Question 4

(T/F) Forms of B6 are not heat sensitive.

Answer 4

FALSE. They are HIGHLY heat sensitive, and can be destroyed with processing and cooking

Question 5

FILL IN THE BLANK

XXXXXXXX form is VERY sensitive to photochemical oxidation and is considered light-sensitive

Answer 5

PLP

Question 6

(T/F) B6 is added to enriched flour, like thiamin, niacin, riboflavin, and folic acid.

Answer 6

FALSE

Question 7

What are food sources of vitamin B6?

Answer 7

1. Beef liver
2. Tuna
3. Salmon

Mainly seafood, fish, and meat products

Question 8

Where does the absorption of B6 primarily occur?

Answer 8

S.I. jejunum

Question 9

Alkaline phosphatase

Answer 9

cleaves off phosphate group (aka dephosphorylated) on PMP and PLP to be absorbed into the enterocytes, via simple diffusion (could be carrier-mediated but it is unclear)

Question 10

How are the plant-forms of B6 absorped?

Answer 10

Plant-based foods = Glycosylated form (have glucoside residue, which must be cleaved off prior to absorption)

They are hydrolyzed partially by a brush-border lactase - PHLORIZIN HYDROLASE

Question 11

(T/F) B6 is produced by microbes in the large intestine; therefore, a minor source.

Answer 11

TRUE; however, there is individual variation, depending on what types of microbes individuals have in the gut microbiome

Question 12

What happens to PL and PM once they are in the enterocyte?

Answer 12

Will be phosphorylated by PYRIDOXAL KINASE to PLP and PMP

The phosphate group being added will trap the CoE. form in the enterocyte

Question 13

How does B6 leave the cell?

Answer 13

PLP and PMP will be dephosphorylated before leaving the enterocyte and entering the portal vein, as PL and PM forms

Question 14

(T/F) Enterocytes are highly metabolically active, rapidly-dividing cells, and may have a need for B6 themselves.

Answer 14

TRUE. By trapping B6 in the enterocyte, it allows the enterocyte itself to use B6 it needs to. If the enterocyte does NOT need the B6, then PLP and PMP will be dephosphorylated and will leave the enterocyte

Question 15

What is the main site for B6 metabolism?

Answer 15

Most tissues can phosphorylate PL, PM, and PN but LIVER is the major site

Question 16

Pyridoxal Kinase

Answer 16

Extremely active in the liver (10x that of phosphatase), meaning PN, PL, PM is rapidly phosphorylated to PNP, PLP, PMP

Question 17

Pyridoxamine oxidase

Answer 17

An enzyme that converts PNP and PMP to PLP.

This is an irreversible reaction.

Liver keeps PLP levels in check through FB inhibition on this enzyme

Question 18

How is PLP spontaneously converted to PL in the blood?

Answer 18

Because the enzyme alkaline phosphatase is present in the blood, so it is an inevitable reaction

Question 19

In what form does B6 leave the liver?

Answer 19

PLP is the major form that is leaving the liver.

Remember, some is converted to PL due to alkaline phosphatase being present in the blood

Question 20

How much of total vitamin B6 in the blood is PLP and PL forms?

Answer 20

90%

Question 21

How is B6 transported in the blood?

Answer 21

Blood PLP is bound to ALBUMIN. Transported in blood both in the plasma and in RBCs

Question 22

What 4 enzymes are dependent on PLP?

Answer 22

1) Serine hydroxymethyltransferase

2) Glycine-decarboxylase

3) Cystathionine beta-synthase

4) Cystathionine y-lyase

Question 23

How is PLP important for glycogenolysis?

Answer 23

Glycogenolysis (breakdown of glycogen)

PLP is a prosthetic group for enzyme GLYCOGEN PHOSPHORYLASE (which is the main enzyme needed to start the breakdown of glycogen)

More specifically, PLP forms a SCHIFF-BASE linkage with lysine residue on enzyme above.

Question 24

Why do we find high levels of PLP in the liver and muscle?

Answer 24

It’s where glycogen is stored

Question 25

In relation to heme synthesis, PLP acts as a CoE. for what enzyme?

Answer 25

Delta-aminolevulinic acid synthase (ALAS)

Question 26

Why is ALAS so important?

Answer 26

For heme to be biosynthesized, we need ALAS enzyme, which takes succinyl-CoA + glycine and converts it to aminoleuvlinic acid (which is a precursor for heme synthesis)

Question 27

Why is heme such an important protein in the body?

Answer 27

It is needed for hemoglobin, myoglobin, cytochromes, nitrogen oxide synthesis, and other biological components in the ETC

Question 28

Branched-Chain Amino Transferase (BCAT)

Answer 28

Enzyme that requires PLP as a CoE. Acts to transaminate BCAAs (valine, isoleucine, leucine) in the mitochondria of muscle

Question 29

Alanine amino-transferase

Answer 29

ALT; PLP dependent enzymes that catalyze the transamination reactions of alanine in AA metabolism

Question 30

Aspartate amino-transferase

Answer 30

AST; PLP dependent enzyme that catalyze the transamination reactions of aspartate in AA metabolism

Question 31

PLP dependent enzymes involved in neurotransmitter synthesis are XXXXXXX reactions

Answer 31

Decarboxylase reactions; thus requiring decarboxylase enzymes which are all PLP dependent

Question 32

What are some clinical signs of B6 deficiency?

Answer 32

-Glossitis and gingivitus -Neuropathy -Microcytic anemia secondary to depressed heme synthesis, resulting in smaller than normal red blood -Possible reduction in neurotransmitter synthesis -Long term deficiency may increase risk for cancer, stroke, and CVD (due to possible abnormal homocysteine metabolism)

Question 33

What medications may impair PLP activity?

Answer 33

Isoniazid (treats TB) Phenelzine (antidepressant; MAOI inhibitor) Gentamicin (abx) Oral contraceptives

Question 34

(T/F) Toxicity of B6 is common.

Answer 34

FALSE. Rare

Question 35

What is the upper tolerable limit for B6?

Answer 35

100 mg/day for adults (this is quite high given supplements only have ~2 mg/daily)

Question 36

What is the best way to assess B6?

Answer 36

Direct measure of PLP in plasma is the easiest and best measure. 20 nmol/L is considered as a cut-off for deficiency Affected by: -----Required to be a fasting blood draw; as carbohydrate intake -----DM and hyperglycemia (can result in a false negative or a sign of deficiency) -----Albumin levels (REMEMBER: albumin carries PLP) -----Alkaline phosphatase enzyme This is used in clinical settings.

Question 37

What is an indirect measurement for B6, where we measure the activity of the enzyme's that are dependent on B6 for activity? HINT: This is only used in the lab setting.

Answer 37

RBC transaminase activity -----AST -----ALT Take blood, add PLP and measure the reaction in AST and ALT, and do a control. If someone is deficient in B6, we will see the enzyme activity REALLY INCREASE because now that they have the CoE. form, they can convert the reaction. So there would be a LARGE difference in the treated and non-treaded groups.