quazi vitamins

7/29/2019 quazi vitamins

1/128

MARGINALCOMPOUDS

semi vitaminsPresented by

NAGI Moh ELFATIH


2/128

number of organic compounds have clear

metabolic functions; they can be synthesized

in the body ,but it is possible that under some

circumstances endogenous synthesis may not

be adequate to meet requirements

Some were considered as vitamines once but

the most suitable term for them all is quasi

vitamins


3/128

The list of quasi-vitamins includes

Factors required for some species other than

man and required in man in certain conditionsCholine

Carnitine

Myo-inositol

Factors with certain metabolic functions but less

evidence for essentiality

Co Q10

Lipoic acid

bioptreins and others


4/128

CARNITINE

-hydroxy--N,N,N trimethylaminobutyrate

quaternary ammonium compound

two stereoisomers L carnitine and D carnitine


5/128

Biologically active forms

L-carnitine


6/128

sources

Diet

Biosynthesis

Supplements


7/128

biosynthesis

From two essential amino acids

lysine and methionine

primarily in the liver and kidneys Requirements for synthesis

Iron

Vitamins C and B6


8/128


9/128


10/128

Dietary Sources

Breast milk --- contains 2895 nmol of

carnitine per milliliter

Red meat

Milk and Dairy products

Fish


11/128


12/128

materials of plant origin tend to be low in

carnitine, whereas those derived from animals

tend to be rich in the factor


13/128

supplements

L-carnitine most widely available and least

expensive

Acetyl L-carnitine

Propionyl L-carnitine


14/128

metabolism

Absorption

active transport dependent on Na+ co-

transport

Passive diffusion

High efficiency

Rapid uptake


15/128

Transport

released slowly from tissues

High soluble in plasma in both the free and

acetylated forms

3089 M taken up, against concentration gradients, by

peripheral tissues by high-affinity, Na+-

dependent transporters located principally in the skeletal muscle, which

contains some 95% of the bodys carnitine


16/128

The L-carnitine level in healthy adults

umol/L

Plasma free L-carnitine level 40~50

Plasma acetyl-L-carnitine 3~6

Plasma acyl-L-carnitine except acetyl-

L-carnitine


17/128

carnitine concentrations of skeletal muscles

are typically 70-fold that of plasma

turnover of carnitine in muscle is relatively

slow( ~8 days) but increased substantially by

exercise


18/128

Excretion

carnitine is highly conserved by the human

kidney, which reabsorbs more than 90% of

filtered carnitine

Renal excretion of carnitine adapts to the level

of carnitine intake

free form or as short-chain acylcarnitine

esters


19/128

Some conditions increase excretion of

carnitine

Propionic aciduria

Methylmalonic aciduria

Supplemental dietary choline


20/128

Metabolic Function transport of fatty acids (fatty acyl-CoA) from the

cytosol into the mitochondrial matrix foroxidation as sources of energy

The fatty acids with chain lengths of 12 or fewercarbons enter mitochondria without the help of

membrane transporters. Those with 14 or more carbons, the majority of

the FFA obtained in the diet or released fromadipose tissue, cannot pass directly through the

mitochondrial membranesthey must firstundergo the three enzymatic reactions of thecarnitine shuttle


21/128


22/128


23/128

The carnitine acyltransferases are actually a

family of related enzymes. Six carnitine

acyltransferases with different but overlappingchain-length specificities have been isolated

from mitochondria

At least five carnitine transporters have beencloned


24/128

Hormone function

Carnitine have biological actions similar to

those of glucocorticoids

bind the glucocorticoid receptor and effect the

receptor-mediated release of cytokines


25/128

Physiological effects

Atherosclerosis

There may be a link between dietaryconsumption of carnitine and atherosclerosis

Antioxidant effects

protective effect against lipid peroxidation of

phospholipid membranes and againstoxidative stress induced at the myocardial andendothelial cell level.


26/128

Health effects

Hepatic function

protect against ammonia-induced encephalopathy in cirrhotics

Renal function

studies have suggested that carnitine administration to dialysis

patients can increase hematocrit, allow a lower erythropoietin

dose, and reduce intradialytic hypotension and fatigue

Diabetes A clinical trial found carnitine to reduce fasting plasma glucose

levels and to increase fasting triglycerides in type II diabetics


27/128

Cardiovascular function

benefit cardiac function

produce effects on prostaglandins that are associated withcardioprotection

reduce myocardial injury after ischemia and reperfusion

Neurologic function

studies have shown that acetylcarnitine treatment can induce

the release of acetylcholine in the striatum and hippocampus,

Alzheimers disease patients carnitine attenuate progression

of several parameters of behavior, disability, and cognitive

performance

reduce attention problems and aggressive behavior in boys

with attention-deficit hyperactivity disorder


28/128

Male reproductive function

Epididymal tissue and spermatozoa typically contain high

concentrations of carnitine Studies indicate that carnitine levels are related to sperm

count, motility, and maturation

carnitine supplementation can improve sperm quality

Thyroid function

Carnitine appears to be a peripheral agonist of thyroidhormone action


29/128

Carnitine deficiency

metabolic disorder in which body levels of

carnitine, is less than what is needed for the

normal function of the body.

True carnitine deficiency is not known to occur

in healthy people

Primary

Secondary


30/128

primary carnitine deficiencyis a rare genetic

disorder caused by a mutation in the protein

that transports carnitine

presents in childhood and can be fatal without

treatment.

Other names for these conditions includecarnitine palmitoyltranserase I or II deficiency

and carnitine-acylcarnitine translocase

deficiency.


31/128

Secondary carnitine deficiency, more

common than primary deficiency,

people at risk

strict vegetarians

protein-energy malnutrition

administration of the anticonvulsant valproic

acid and other drugs

metabolic organic acidemias acidurea

premature infants

patients undergoing hemodialysis


32/128

Signs and Symptoms of Deficiency

Some people with primary carnitine deficiency

are asymptomatic

Symptomatic disease appears as

liver dysfunction

Cardiomyopathy and cardiomegaly

Muscle fatigue and weakness

abdominal cramps

Hypoketotic hypoglycemia

Diarrhea

Anemia


33/128

Diganosis of carnitine deficiency

Measurement of plasma carnitine levels of individuals

with carnitine deficiency will show extremely reducedplasma free carnitine levels (


34/128

Treatment of carnitine deficiency

high dose carnitine supplementation, which

must be continued for life.

Individuals who are identified and treated at

birth have very good outcomes, including the

prevention of cardiomyopathy


35/128

CHOLINE

2-hydroxy-N,N,N-trimethylethanaminium

quaternary ammonium compound

freely soluble in water and ethanol, but

insoluble in organic solvents.

strong base

methyl donor ==prominent feature of itschemical structure due to its triplet of methyl

groups


36/128


37/128

Dietry forms widely distributed in foods

mostly in the form ofphosphatidylcholine

(lecithin),

Some dietary choline is present as thefree

base or sphingomyelin


38/128

sources in diets

egg yolk

glandular meats

(e.g., liver, kidney, brain)

soybean products,

wheat germ

peanuts


39/128


40/128

supplements

Available as choline salts

Added to infant formula also


41/128

metabolism

Digestion

Choline is released from phosphatidylcholine by

hydrolysis in the intestinal lumen, an action of

phospholipases 3 type of phospholipases act on phosphatidylcholine

Phospholipase A2

Phospholipase A1 Phospholipase B


42/128

O CH2C R

O

CHOCR

O

H2C O P O X

O

Phospholipase A1

Phospholipase A2

Phospholipase C Phospholipase D

Cleavage sites of phospholipases

PhospholipaseB


43/128

most of the phosphatidylcholine that is ingested

is absorbed as lysolecithin

lysolecithin is reacylated to phosphatidylcholine in theintestinal mucosal cells

30% of dietary phosphatidylcholine is absorbed intact

into the lymphatic system bound to chylomicron

the resr is converted to glycerylphosphorylcholine in the

intestinal mucosa and to free choline in the liver


44/128

When free choline is consumed a large amount (e.g.,

nearly two-thirds) is catabolized by intestinal

microorganisms to the end product trimethylamine

The remaining portion is absorbed intact

Choline is absorbed in the upper portion of the small

intestine by a saturable, carrier-mediated process


45/128

Hgffd


46/128

Tissue distribution

present in all tissues as an essential

component of phospholipids in membranes of

all types.

stored in the greatest concentrations in brain,

liver, kidney in forms of phosphatidylcholine

and sphingomyelins

Placenta accumulate large amounts ofacetylcholine


47/128

Biosynthesis

three ways of phosphatidylcholine

biosynthesis:

Methylation of ethanolamine,

Reaction of cytidine diphosphate

Phospholipid base exchange


48/128


49/128


50/128

Choline is released in free form in the tissues

by the actions ofphospholipase C peripheral tissues also contain phospholipase

B activity and can therefore produce

glycerylphosphorylcholine The brain also contains phospholipase D,

which cleaves free choline directly


51/128


52/128

Metabolic Functions

As phosphatidylcholine

A structural element of biological membranes

A promoter of lipid transport (as a lipotrope)

Surfactant


53/128


54/128


55/128

As acetylcholine, it is a neurotransmitter, occurring

primarily in the parasympathetic nervous system

,autanomic ganglia, neuromusclar junction and CNS


56/128

As a component of platelet-activating factor

it is important in clotting, inflammation,

uterine ovum implantation, fetal maturation,

and induction of labor

As a component of plasmalogen, it has a role

in myocardial function


57/128

As a source oflabile methyl groups, after its

irreversible oxidation to betaine,

it is a source of labile methyl groups fortransmethylation reactions in the formation of

methionine from homocysteine,

This function links choline to folate metabolism

choline constitutes an important dietary source of

labile methyl groups for homocysteine

transmethylation


58/128


59/128


60/128


61/128

Health Effects

choline loading may be beneficial to patients with diseasesinvolving deficiencies of cholinergic neurotransmission

1. enhance cognitive performance,

2. increase electrophysiological responsiveness;

3. provide some protection against alcohol and otherneurotoxic agents

4. help in the treatment of tardive dyskinesia

5. success to improve free memory in subjects without

dementia6. diminish short-term memory losses associated with

Alzheimers disease


62/128

deficiency

Risk of deficiency

Poor nutrition, imbalance in the diet

liver disease

methionine,folic acid and vitamin B-3

deficiency

Methotrexate


63/128

Mild choline deficiency can cause

fatigue,

insomnia,

frequent memory loss,

and nerve-muscle imbalances.

f


64/128

Extreme choline deficiency can cause

liver dysfunction,

cardiovascular disease,

impaired growth,

abnormalities in bone formation,

lack of red blood cell formation,

infertility,

respiratory distress and failure to thrive in newborns,

kidney failure, anemia, and high blood pressure.


65/128

Toxicity

very low

Appears as symptoms of

Growth depression,

impaired utilization of vitamin B6

dizziness, nausea, and diarrhea


66/128

Myo inositol

Inositol is a carbohydrate

It is sugar alcohol

water-soluble hydroxylated, cyclic six-carbon

compound

nine possible stereoisomeric forms

Myo inositol is the only biologically active

form


67/128

Dietary Sources

occurs in foods and feedstuffs in three forms:

free myo-inositol,

phytic acid and

Inositol containing phospholipids


68/128

The richest sources ofmyo-inositol are the

seeds of plants

Predominant form occurring in plant materials

isphytic acid

Because most mammals have little or no

intestinal phytase activity, phytic acid is poorlyutilized as a source of either myo-inositol or

phosphorus

I i l d t i it l i f f


69/128

In animal products, myo-inositol occurs in free form

as well as in inositol-containing phospholipids

The richest animal sources of inositol are organmeats


70/128

Human milk is relatively rich in myo-inositol

(colostrum, 200500 mg/liter; mature milk,

100200 mg/liter) It is added to many prepared infant formulas


71/128

Biosynthesis

from Glucose 6 phosphate

in the kidneys 4 g/day


72/128

supplements


73/128

Absorption

active transport

uptake ofmyo-inositol from the small intestine iscomplete

absorption of phytic acid, however, depends onthe ability to digest that form and on theamounts of divalent cations in the diet/meal

Dietary cations (particularly Ca2+) can reduce the

utilization of phytate by forming insoluble (and,thus, nondigestible and nonabsorbable) phytatechelates

Absorption of phospholipid m o inositol is


74/128

Absorption of phospholipid myo-inositol; is

probable that it is analogous to that of

phosphatidylcholine


75/128

Transport

Transported in the blood predominantly in the freeform;

A small but significant amount of phosphatidylinositol

(PI) is found in association with the circulating

lipoproteins


76/128

Tissue uptake

Free myo-inositol appears to be taken up

by active transport process in some tissues

(kidney, brain)

by carrier-mediated diffusion in others (liver).

The active process requires Na+ and energy,

and is inhibited by high levels of glucose.


77/128

Metabolism Free myo-inositol is converted to PI within cells either by

de novo synthesis by reacting with the liponucleotide

cytidine diphosphate (CDP)-diacylglycerol,or by an

exchange with endogenous PI

Phosphatidylinositol sequentially phosphorylated to themonophosphate (phosphatidylinositol 4-phosphate, PIP)

and diphosphate (phosphatidylinositol 4,5-diphosphate,

PIP2) forms by membrane kinases


78/128

i it l t i i h h li id i h d i


79/128

myo-inositol-containing phospholipids enriched in

stearic acid at sn1-position and arachidonic acid at

sn2-position

turnover of the myo-inositol phospholipids


80/128

turnover of the myo inositol phospholipids

cellular phosphomonoesterases catabolize PIPs to yield

PI.

PI synthetase functions (in the reverse direction) to

break down that form to yield CDP-diacylglycerol and

myo-inositol

The kidney perform most of the catabolism ofmyo-inositol, first clearing it from the plasma and converting

it to glucose and, then, oxidizing it to CO2 via the

pentose phosphate pathway

Metabolic Functions


81/128

Metabolic Functions

active form is phosphatidylinositol,

effecter of the structure and function ofmembranes

enzyme modulater

source of arachidonic acid for eicosanoidproduction

mediator of cellular responses to externalstimuli

e ec er o e s ruc ure an unc onof membranes


82/128

of membranes

activator of a microsomal Na+,K+ ATPase

effective anchor for the hydrophobic attachment of proteins

to membranes

Regulation of Vesicle Transport

Rearrangement of actin cytoskeleton Recruitment of Tyrosine kinases

mediator of cellular responses tol i li


83/128

external stimuli


84/128

enzyme modulater


85/128

en yme modulater

constituent of acetyl-CoA carboxylase

stimulator of tyrosine hydroxylase

Factor bound to alkaline phosphatase and 5-nucleotidase

membrane anchor for acetylcholinesterase

Li i A id


86/128

Lipoic Acid

organosulfur compound derived fromoctanoic acid.

contains two sulfur atoms (at C6 and C8)

connected by a disulfide bond

Di t S


87/128

Dietary Sources present in a wide variety of foods but generally at low levels.

The best sources are tissues rich in mitochrondia (e.g., heart,

kidney)

tissues rich in chloroplasts (i.e., dark green leafy vegetables)

M t b li F ti


88/128

Metabolic Functions

Coenzyme essential cofactor for the oxidative decarboxylations of -

keto acids where, linked to the -amino group of a lysine

residue of the enzyme dihydrolipoyl transacetylase, it is one

of several prosthetic groups in multienzyme complex. In thatcatalysis, the amide form, lipoamide, undergoes reversible

acylation/deacylation to transfer acyl groups to CoA as well as

reversible redox ring opening/closing, which is coupled with

the oxidation of the -keto acid


89/128

Antioxidant


90/128

The ability to undergo

interconversion between disulfide(lipoic acid) and sulfhydryl(dihydrolipoic acid) forms enablesthis metabolite to function as a

metabolic antioxidant, quenchingreactive oxygen species and otherfree radicals and chelating prooxi-dant metal ions. Its function in thisregard is related to those of other

metabolic antioxidants in thenetwork of protection againstoxidative stress.

Antioxidant

H lth Eff t


91/128

Health Effects

it has been proposed that lipoic acid may have valuein the prevention and/or treatment of other chronic

dis-eases associated with oxidative stress

Recent interest has centered on the prospective

benefits of lipoic acid in diabetes andneurodegenerative diseases

Coenzyme Q


92/128

Coenzyme Q10

Ubiquinone

tetra-substituted 1,4-benzoquinone

derivativeswith isoprenoid side

chains of variable length

essential component of themitochondrial electron transport

chains of most prokaryotic and all

eukaryotic cells

sources


93/128

sources

Rich sources of dietary coenzyme Q10 include mainly

meat, poultry, and fish. Other relatively rich sources

include soybean and canola oils, and nuts. Fruits,

vegetables, eggs, and dairy products

Supplements

Biosynthesis


94/128

Biosynthesis

Coenzyme Q10 is synthesized in most tissues.

Requierment

mevalonate,

tyrosine,

molecular oxygen,

S-adenosylmethionine.

endogenous tissue biosynthesis is sufficient to

support membrane saturation levels

Metabolism


95/128

Metabolism

Absorption

ubiquinones are absorbed, transported andtaken up into cells by mechanisms analogousto those of the tocopherols

Tissue distribution

In all membranes in the cell.

Relatively great concentrations of CoQ10are

found in the liver, heart, spleen, kidney,pancreas, and adrenals.

Tissue ubiquinone levels increase under the


96/128

influence of oxidative stress, cold acclimation,

and thyroid hormone treatment, and decrease

with cardiomyopathy, other muscle diseases, and

aging


97/128


98/128


99/128

Metabolic Function


100/128

Metabolic Function

Mitochondrial respiratory chain component

electron acceptors for complexes I and II of

mitochondrial electron transport chains. They pass

electrons from flavoproteins (e.g., NADH or succinic

dehydrogenases) to the cytochromes via cytochrome

b5

They perform this function by undergoing reversible

reduction/ oxidation to cycle between the 1,4-quinone (oxidized) and 1,4-dihydroxybenzene

(reduced) species

Antioxidant


101/128

membrane-bound antioxidant

protects and thus spares -tocopherol in subcellularmembranes.

Along with -tocopherol, -carotene, and selenium,

CoQ10 has been shown to provide significant

protection from lipid peroxidation in animals.

In some tissues (e.g., liver) its effect appears to be

greater than those of the other antioxidant nutrients.

Health effects


102/128

Clinical trials with humans have indicated benefits ofsupplemental CoQ10 of several types

Modest improvements in symptoms with Parkinsons diseasepatients.

reduce headache frequency

reduce dyspnea, edema, and the frequency of hospitalization

in Congestive heart failure decrease systolic and diastolic blood pressure in hypertensive

patient

reduce subsequent myocardial events and cardiac deathsafter myocardial infarction

improve endothelial function of peripheral arteries ofdyslipidemic patients with type II diabetes.

Tetrahydrobiopterin


103/128

y p

Tetrahydrobiopterin can be synthesized from GTP

It is the coenzyme for mixed function oxidases:

phenylalaninehydroxylases ,

tyrosine hydroxylases, tryptophan hydroxylases;

alkyl glycerol monoxygenase,

nitric oxide synthase

. In addition to its coenzyme role, tetrahydrobiopterin has adirect effect on neurons, acting to stimulate dopamine release

via a cAMP-dependent protein kinase and a calcium channel


104/128


105/128

A deficit in tetrahydrobiopterin biosynthesis and/or


106/128

regeneration can result inphenylketonuria (PKU)

from excess phenylalanine concentrations or

hyperphenylalaninemia (HPA).

The chronic presence of PKU can result in severe

brain damage, including symptoms of mental

retardation, microcephaly, speech impediments suchas stuttering, slurring, and lisps, seizures or

convulsions, and behavioral abnormalities, among

other effects

Glutathione


107/128

Glutathione

Glutathione (gamma-glutamyl-cysteinyl-glycine )

Tripeptide

It is an antioxidant, preventing damage to

important cellular components caused by

reactive oxygen species such as free radicals

and peroxides


108/128

gamma peptide linkage between the amine

group of cysteine (which is attached by normalpeptide linkage to a glycine) and the carboxyl

group of the glutamate side-chain

Biosynthesis


109/128

Biosynthesis

not an essential nutrient (meaning it does not have to beobtained via food), since it can be synthesized in the body

from the amino acids L-cysteine, L-glutamic acid, and glycine.

all cells in the human body are capable of synthesizing

glutathione,

liver is the main organ of glutathione synthesis

Glutathione exists in both reduced (GSH) and


110/128

oxidized (GSSG) states

Food sources


111/128

Food sources

Foods containing glutathione and glutathione-stimulating chemicals

Tomatoes, garlic, onions and green peppers

Function


112/128

Function

Glutathione has multiple functions:

It is the major endogenous antioxidant

produced by the cells, participating directly in

the neutralization of free radicals and reactiveoxygen compounds, as well as maintaining

exogenous antioxidants such as vitamins C and

E in their reduced (active) forms

GSH is known as a substrate in both


113/128

GSH is known as a substrate in both

conjugation reactions and reduction reactions,

catalyzed by glutathione S-transferaseenzymes in cytosol, microsomes, and

mitochondria. However, it is also capable of

participating in non-enzymatic conjugationwith some chemicals.

It is used in metabolic and biochemical


114/128

It is used in metabolic and biochemical

reactions such as

DNA synthesis and repair,

protein synthesis,

prostaglandin synthesis,

amino acid transport,

and enzyme activation.

Regulation of the nitric oxide cycle which is


115/128

Regulation of the nitric oxide cycle, which is

critical for life but can be problematic if

unregulated

It has a vital function in iron metabolism.

Glutathione as antioxidant


116/128

Glutathione as antioxidant


117/128


118/128


119/128

HHHH

phytochemicals


120/128

p y oc e ca s


121/128


122/128


123/128

Functions


124/128

Hormonal action - Isoflavones, found in soy, imitate human estrogensand help to reduce menopausal symptoms and osteoporosis.


125/128

and help to reduce menopausal symptoms and osteoporosis.

Stimulation of enzymes - Indoles, which are found in cabbages,

stimulate enzymes that make the estrogen less effective and couldreduce the risk for breast cancer. Other phytochemicals, whichinterfere with enzymes, are protease inhibitors (soy and beans),terpenes (citrus fruits and cherries).

Interference with DNA replication - Saponins found in beans interfere

with the replication of cell DNA, thereby preventing the multiplicationof cancer cells. Capsaicin, found in hot peppers, protects DNA fromcarcinogens.

Anti-bacterial effect - The phytochemical allicin from garlic has anti-bacterial properties.

Physical action - Some phytochemicals bind physically to cell wallsthereby preventing the adhesion of pathogens to human cell walls.


126/128


127/128

There are currently many phytochemicalsin clinical trials for a variety of diseases.

Lycopene from tomatoes, for example, has beentested in human studies for cardiovascular

diseases and prostate cancer. These studies,however, did not attain sufficient scientificagreement to conclude an effect on any disease.

Lutein and zeaxanthin are suspected to

inhibit macular degenerationand cataracts, therewas insufficient scientific evidence from clinicaltrials for such specific effects or health claims.


128/128

quazi vitamins

Documents