introduction to b-vitamins: role of b-vitamins in metabolic pathways sept 10, 2014

INTRODUCTION TO B-VITAMINS:

ROLE OF B-VITAMINS IN METABOLIC PATHWAYS

Sept 10, 2014

We get energy on a daily basis fromcarbohydrates, lipids, and proteins.

What events must occur, to enableus to employ these dietary componentsfor energy?

NIACIN is vitamin needed for a great manyevents in energy metabolism.

Two forms of niacin in the diet are shown: these areprecursors for NADH and NADPH

NIACIN AS A COMPONENTOF NADH AND NADPH:

These participate in >200biochemical reactions that

are essential for health!

EACH RED ARROWIS A STEP IN FORMATIONOF ATP FROM GLUCOSE,THAT USES NIACIN

FADH2 is a riboflavin-dependentcomponent. The FADH2 produced

also contributes electronsfor ATP synthesis by the ETC

GLYCOLYSIS: The molecular steps are easily seen.

ROLE FOR NIACIN

USEFUL EXERCISE:Draw out the intermediatesin the TCA cycle

O

H2C

H2C

C

CO

O

CO

O

O

H2C

H2C

C

CO

O

SCoA

alpha-ketoglutarate succinyl-CoA

NAD+

Acetyl-CoA

NADH

CO2

REACTION CATALYZED BY THE ENZYMEa-KETOGLUTARATE DEHYDROGENASE(PANTOTHENIC ACID is involved, will be discussed)

NADH (which contains niacin) carries most of the electrons from the TCA to the electron-transport chain.

The NAD+ is regenerated, to be used again MANY times.

FromTCA

This is VERY simplified, of course. It really justshows the REACTANTS and the PRODUCTS.

The niacin functional group as a redoxdonor/acceptor of electrons

CH3 - C - COO-

H

OH?

Lactate

NAD+

Reaction catalyzed by LDH

CH3 - C - COO-

O?

Pyruvate

NADH

Another reaction catalyzed by LDH

Glutamate is the main amino acid that donates nitrogento the urea cycle. NADH is required for this reaction.

Niacin (as NAD)is required for themetabolism ofethanol.

The metabolic fateof lysine – HOW MANYniacin-dependent steps?

Amino acids are degradedfor energy in normalmetabolism, we will discussin some detail.

Notice the Acetyl-CoA product,which can be used by the TCAcycle to make ATP.

OTHER B-VITAMINS HAVE ESSENTIAL ROLES IN ENERGY METABOLISM

Pantothenic acid: allsteps that use CoA

Thiamine

Riboflavin

Thiamine: as provided in the diet

The active form of thiamine in metabolism

SEPARATEENZYMES EXISTTO ACTIVATEEACH B-VITAMIN:

Thiamine is modifiedby addition oftwo PO4 groups

SEVERAL ENZYMES WORK TOGETHER IN THEPYRUVATE DEHYDROGENASE COMPLEX:

WHAT IS THE FATE OF THE 3 CARBONS INTHE INITIAL PYRUVATE MOLECULE?

Wet Beriberi: edema Wet Beriberi: edema is a common feature.is a common feature.

What is the What is the diagnostic challenge?diagnostic challenge?

Pellagra: dermatitis is typicalPellagra: dermatitis is typical

Pellagra/before and after treatment with high-dose niacin: which biochemical

steps are disturbed, that involve niacin?

This graphic shows that somedietary tryptophan is convertedto NIACIN.

The yield is is about 1 mg ofniacin, for 60 mg of tryptophan.

Corn is a problem becauseits niacin content is often not bioavailable, and because corn is low in tryptophan.

The niacin RDA (20 mg) is basedon a lot of our niacin (another20 mg) coming from tryptophan.

People who cannot make niacinare given about 50 mg/day.

MICRONUTRIENT DEFICIENCY: Often very non-specific.

How can we be prepared to diagnose these disorders?

USEFUL STUDY ASSIGNMENT:

-Suppose you ate a VERY limited diet, withfoods that are NOT fortified. What nutrientswould be deficient?

-corn

-potatoes

-white rice

-wheat

This can happen during a famine, where there is a sharpreduction in the diversity of the diet.