CHOLINE

GOPI.M M.V.Sc., Scholar, Dept. of Animal Nutrition

Introduction
History:

Named by Strecker (1862).

Structure was established by Bayer (1867).

Choline recognized as essential, long before most other vitamins were discovered.

 Is Choline A Vitamin? Tentatively classified as a B-complex vitamin.

But, does not satisfy a strict definition of the vitamin, which is: An organic substance of nutritional nature present in low concentration as a component of enzymes . . . and may be derived externally to the tissue or intrinsic biosynthesis.
Syn in liver, req in high amounts & funs as structural compound rather than as coenzyme.

Structure of Choline:

(CH3)3N+CH2CH2OH

Chemical structure & properties

Pure choline is a colorless, viscid, strongly alkaline liquid, hygroscopic.

Soluble in water, formaldehyde & alcohol.

Choline chloride white crystals, very soluble in water & alcohols. Distributed in nature as free choline, ACh & more complex phospholipids. Integral part of the lecithin.

Biosynthesis of Choline
Serine

Glycine

Ethanolamine

Monomethyl ethanolamine

Dimethyl ethanolamine

Choline

Metabolism
Choline present in the diet in the form of lecithin as free base or spingomyelin.

Released by digestive enzymes of the GI tract.

Only one- third of ingested choline appears to be absorbed intact. Less urinary trimethylamine is excreted in the urine 1224 hr after consumption.

Metabolic pathway

Choline : Methionine interrelation

Choline & Methionine two major methyl donors in metabolism.

Aid in the synthesis of Methionine from transmethylation of homocysteine. Demethylation of Methionine to homocysteine provide methyl groups for choline synthesis.

What is methylation? CH3 are single C units needed for syn of essential metabolites (e.g. Methionine, Carnitine, Creatinine, phospholipids, RNA and DNA).

Animals require a constant supply of dietary CH3.

The requirement for CH3 increases under stressful conditions such as heat and disease stress CH3 cannot be synthesised by the animal, and so must be provided in the diet .

CH3 are transferred from one substance to another via the methylation cycle.
Methionine and choline also participate in the methylation cycle

Trimethylamine & fishy taint

Trimethylamine(TMA) has fishy taint produced from choline by action of intestinal microbes. Rapeseed meal contain sinapine, the choline ester of sinapinic acid, a precursor of TMA.

 Choline and its metabolites are needed for 3 main physiological purposes: Structural integrity and signaling roles for cell membranes. Cholinergic NT- ACh (acetylcholine synthesis).

Major source for methyl groups via its metabolite, trimethylglycine (betaine) that participates in the S-adenosylmethionine synthesis pathways.

Structural integrity of cell membranes

Choline is used in the synthesis of the phospholipids, phosphatidylcholine and sphingomyelin, which are structural components of cell membranes.

Cell signaling

Choline-containing phospholipids, phosphatidylcholine and sphingomyelin, are precursors for the intracellular messenger molecules, diacylglycerol and ceramide.
Two other choline metabolites, platelet activating factor (PAF) and sphingophosphorylcholine, are also known to be cell-signaling molecules.

Nerve impulse transmission

Choline is a precursor for ACh, an important NT involved in muscle control, memory, and many other functions.

Lipid (fat) transport and metabolism

Fat and cholesterol consumed in the diet are transported to the liver by lipoproteins called chylomicrons. In the liver, fat and cholesterol are packaged into lipoproteins called VLDL for transport through the blood to tissues that require them. Phosphatidylcholine is a required component of VLDL particles.

Without adequate phosphatidylcholine, fat and cholesterol accumulate in the liver.

Choline is refered as a lipotropic factor.

 Source of labile methyl groups, which function in the formation of Methionine from homocysteine & of creatine from guanidoacetic acid.

Requirements
Synthesized by most species.

Factors influencing requirement are methionine, betaine, myo- inositol, folacin& vit B 12 or combination of different levels. Composition of fat, carbohydrate & protein, age, sex, caloric intake & growth rate of animals influence lipotropic action of choline & thereby requirement.

Requirements
Animal Purpose

Requirement 260mg/kg

Calf milk replacer

Dairy cattle

Adult

Microbial synthesis

Sheep

Adult

Microbial synthesis

C. Choline requirements:

A. In general: 1) Requirements can be met by: a) dietary supplemental choline or from typical feedstuffs, and b) choline synthesis in the body. 2) Affected by: a) Dietary methionine (an other principal methyl donor) level. b) Folacin level - Folacin in formation of a labile methyl group. c) Vitamin B12 level - B12 in transfer of a methyl group to tetrahydrofolate.

Natural sources Richest sources

Egg yolk (1.7 %), glandular meat(0.6% ),brain & fish (0.2 %) Germ of cereals (0.1%),legumes (0.2-0.35%) & oil meals. Poor sources Corn, most fruits & vegetables.

The availability of choline in natural feedstuffs, soybean meal & whole soybeans may contain 60 to 75% available choline.
Supplemental choline: 1) Choline chloride contains 86.8% choline (a 70% liquid or 25-60% dry powder). 2) Choline bitartrate contains 48% choline.

Choline as Choline chloride are corrosive, so special storage is req. Hygroscopic & not suitable for incorporation into vitamin premix & so added directly to poultry feeds.

Deficiency
General Poor growth Fatty liver Perosis Poultry: Laying hens-reduction in egg production & increase fat content in liver

 Perosis: The outstanding sign of choline deficiency in chicks and poults is perosis.
Perosis is first characterized by pinpoint hemorrhages and puffiness on the hock joint, & a rotation of the metatarsus.
The metatarsus continues to twist and may become bent or bowed so that it is out of alignment with the tibia. The leg cannot adequately support the weight of the bird. The articular cartilage is displaced, and the Achilles tendon slips from its condyles.

Young pigs:

Unthriftiness,poor conformation (short-legged & pot-bellied), lack of coordination in movements. Fatty infiltration of liver.
spraddled hind legs

Spraddled hind legs in swine

TOXICITY
Salivation, Trembling, Jerking, Cyanosis, Convulsion and Respiratory paralysis

Choline:

1) Growing chickens can use betaine interchangeably with choline for the methylation function, but it cannot replace choline to prevent perosis. Still, can spare choline! 2) Also, vitamin B12 can reduce the choline requirement.

Betaine
Betaine can spare choline.

Wheat & wheat byproducts relatively high in betaine can meet the part of the choline req for poultry.

Choline Vs Betaine
Choline is converted to betaine which then provides a methyl group to convert homocysteine to methionine.
Betaine carries out this methylation function of choline more efficiently. But Other functions of choline (synthesis of phospholipids and acetylcholine) cannot be replaced by betaine.

Betaine reduces the impact of heat stress on broiler performance

What is Betaine?
Betaine is a naturally occurring substance found in a variety of plant and animal species

Betaine plays an important role in maintaining osmotic balance in sugar beet and in other plant and animal species

Betaine has two roles

1. Osmolyte Betaine aids in the maintenance of water and ion balance in living cells. 2. Methyl donor Betaine donates essential methyl groups in a number of biochemical reactions (e.g. synthesis of DNA/RNA, carnitine etc). Betaine is a more efficient methyl donor than either methionine or choline

Betaine an osmolyte
Maintains water balance in cells and helps prevent cellular dehydration

Quickly transported into the cell or synthesized in the cell during osmotic stress
Increases osmotic strength of the cell

Protects macromolecules (e.g. cellular enzymes) from osmotic inactivation and cell death

Hyperosmotic stress without compensatory mechanisms

Water diffuses out of the cell

Increased electrolyte concentration in the cell

Lower electrolyte concentration

Water diffuses out of the cell

Depressed metabolism

Cell shrinks

Water no longer diffuses out of the cell

Electrolyte

Hyperosmotic stress & compensation with both ion pumps & betaine

Water balance maintained

H+ Na+ K+

Stable electrolyte concentration in the cell

Cell volume maintained

Lower energy cost

HCO3Cl -

Na+
Stable metabolism

Betaine
Ion pumps

Role of an osmolyte in heat stress

Heat stress disturbs the birds water and electrolyte balance Osmolytes improve a cells ability to retain water during heat stress

 Betaine consistently improves the hydration and integrity of the gut wall, manifested as reduced coccidiosis lesion scores

and reduced water loss

This water retention will results in higher muscle gain during summer or heat stress.

Uses:
Carcass yield improvements, by increased breast yield
Increased gut tensile strength, reduction in carcass contamination during processing Reduced shrink losses in transport of broilers Lower mortality Energy sparing. Use in development antibiotic free growth promotants and coccidiostats withdrawal.

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