Vitamins and Minerals

Sept 18, 2013

BIOCHEMISTRY OFVITAMIN B6

Form of Vit B6(PLP) that is part of enzymes. All the other formsin the diet also support the B6 requirement (about 2 mg/day).

The RDA for adults, for B6, is 2 mg. Vitamin B6is added to some foods (such as breakfastcereal). One serving TOTAL cereal meets the RDA;one serving of Cheerios is 25% of the RDA.

By contrast, bakery products in the US are enriched with thiamine, niacin, riboflavin, and folate, but not usually B6.

Good sources: chicken, beef, fish and other animal products.Bananas, potatoes with skin, collard greens, and some legumes, are also useful. Deficiency is not common in the United States. (The vegan diet may be somewhat low in B6)

Milk is not a very good source (0.5 mg/quart) and the B6 isDEGRADED if milk is boiled to make formula; this may havecaused infant seizures in the early 1950’s.

Americans burn 100 grams of amino acids/day(derived from protein) for energy. That is 400calories – sometimes 20% of total energy!

What step is necessary, for those amino acidsto be used for metabolic energy, such as the synthesis of ATP?

Pyruvate, and everymolecule in the TCAcycle, contains onlycarbon, hydrogen,and oxygen.

But amino acids allcontain NITROGEN.

What is the strategythat is used?

MOST OF THESECAN BE USEDFOR ENERGY, IF THE AMINO GROUP IS REMOVED

The chemistry oftransamination beginswith the DONOR amino acid,which is going to provide the amino group.

This is followed bya set of reactionswith the enzyme,which we will discuss.

Donor amino acid

Amino groupfrom donor

The amino group isis transferred to ketoacid, which becomesthe new amino acid.

The keto acid is theACCEPTOR OF the amino group.

New amino acid

What happened with the FIRST amino acid?A keto-acid is formed.

AMINO KETO NEW KETO NEW AMINO ACID ACID ACID ACID

Beside a new amino acid (GLUTAMATE), a new ketoacid is formed (PYRUVATE). (the new keto acid, from reaction series #1). This reaction is done by the enzyme ALANINE TRANSAMINASE (ALT).

What can be done with pyruvate, in metabolism?

WE WILL DISCUSS THE DIAGRAM IN CLASS,WITH DETAILS ON THE BOARD

After several weeks of HepA infections, there is a largerelease of alanine-transaminase (ALT) to the bloodstream,from damaged liver cells.

What information does that provide about what’s happening inside the liver cell?

Vitamin B6 (as PLP) is also a cofactor for the DECARBOXYLASE reaction.

VITAMIN B6 IS REQUIRED TO CONVERT GLUTAMATE TO THE KEY NEUROTRANSMITTER, GABA.

What could happen if there was a deficiency of B6?

These patients require 100 mg/day of vit B6to avoid seizures; the RDA is ~2 mg/dayfor healthy people with normal metabolism.

Why do they require so much dietary B6?

Plecko, et al, Human Mutation, 28: 19-26,2007

L-PIPECOLIC ACID ACCUMULATES –BECAUSE OF THELACK OF THISENZYME

Piperidine-6-carboxylatecomplexes with PLP, andcreates a PLP “deficiency”

LYSINE CATABOLISM

A large amount of piperidine-6-carboxylate accumulates because of the enzymatic defect in lysine catabolism. In the brain, this makes a complex with B-6, and the brain has trouble making enough GABA.

The result is seizures, because CNS function requires GABA.

If these people are given very large doses of B-6 (100 mg/day), then enough is supplied to the brain to support GABA synthesis.

There are a large number of disorders, each affecting small numbers of people, where those individuals require much larger amounts of a vitamin or mineral to maintain health, than do people without that metabolic disorder.

This would be an interesting topic for class review.

How common is B6 deficiency in humans?

It’s one of the more widely-available B-vitamins, so deficiency does not seem to be a major public health problem (except of course for individuals with metablic problems, such as accumulation of pipecolic acid in the brain).

In the early 1950’s, when formula was sometimesBOILED to achieve sterile baby food, there weresome infants who had seizures. We know that mechanism, from the demonstrated role for B6in sythesis of GABA.

OTHER KEY ROLES FOR VITAMN B6:

-synthesis of heme, starting with delta-amino- levulinic acid (B6-deficiency can contribute to anemia)

-conversion of tryptophan to niacin

-folate metabolism (Critical role!)

-synthesis of several neurotransmitters

THIAMINE DEFICIENCY

MAY BE EASIER TO DIAGOSE THAN SOME OF THE OTHER MICRONUTRIENT DEFICIENCIES, BECAUSE LACTIC ACID ACCUMULATESIN THE BLOODSTREAM.

LACTIC IS VERY EASY TO MEASURE ON ASTANDARD CLINICAL CHEMISTRY ANALYZER

From paper: Thiamine deficiency and acidosis

Use of hemodialysis and bicarbonate is very standardif the causes of acidosis is renal failure!

Thiamine-dependent steps in conversionof pyruvate to ATP

Thiamine

The first reaction (#1) requires thiamine to go forward.

If this step is blocked, what happens to the pyruvate?

Paper on Anorexia Nervosa: need to relyon “general symptoms” for diagnosis

NIACIN DEFICIENCY CAN BE DIAGNOSED(WITH DIFFICULTY) BY A TEST FORMETABOLITES IN THE URINE.

I CAN PROVIDE REFERENCES TO THIS PROCEDURE.

WE CAN IN GENERAL CONCLUDE THATDIAGNOSIS OF MICRONUTRIENT DEFICIENCIESIS A MAJOR CLINICAL CHALLENGE.