Sources of Vitamin K

Phylloquinone: Green leafy vegetablesMenaquinone: Intestinal bacteria

Intestinal bacterial synthesis meets the daily requirement of vitamin K even without dietary supplement

Menadione: synthetic form

Functions of Vitamin KCoenzyme for the synthesis of

prothrombin and blood clotting factors in the liver

Factors dependent on Vit K :Factor II (Prothrombin)Factor VII Factor IX (Christmas Factor)Factor X (Stuart Prower factor )

Active form

Warfarin

Prothrombin – platelet interaction

Functions of Vitamin KProthrombin – platelet interaction

Carboxylated prothrombin contains two carboxylate groups (COO–)

These groups bind to Ca2+ forming prothrombin-calcium complex

The complex then binds to phosholipids on the surface of platelets (important for blood clotting)

Converting prothrombin to thrombin and initiating clot formation

Functions of Vitamin K

Synthesis of -carboxyglutamate in osteocalcinOsteocalcin is a bone proteinMay have a role in bone formation and

mineralization-carboxyglutamate is required for

osteocalcin binding to hydroxyapatite (a mineral) in the bone

Causes of Deficiency of Vitamin KDeficiencies are rare: it is synthesized by

the intestinal bacteriaMalabsorption of lipids leads to vitamin K

deficiencyProlonged Antibiotic therapy &

Gastrointestinal infections with diarrhoea

Destruction of Bacterial flora

Vitamin Deficiency

Deficiency of Vitamin K

Deficiency most common in newborn infantsNewborns lack intestinal floraHuman milk cannot provide enough

vitamin KSupplements are given by injection

Clinical Manifestations of Deficiency

Hemorrhagic disease of the newbornBruising tendency, ecchymotic patches

(bleeding underneath the skin)Mucus membrane hemorrhagePost-traumatic bleeding / internal bleedingProlonged prothrombin time & delayed

clotting timeTreatment of pregnant women with Warfarin

can lead to Fetal bone deformities

Hemorrhagic disease

of the newborn

Role of ThiamineThiamine pyrrophosphate is the coenzyme of :

- Pyruvate dehydrogenase [Pyruvate Acetyl CoA +

CO2 ]- Alpha ketoglutarate dehydrogenase [Alpha ketoglutarate Succinyl CoA

+ CO2 ]- Transketolases [In HMP shunt pathway ]

Deficiency Manifestations of Thiamine

Deficiency of Thiamine leads to beriberi.Early symptoms are :

AnorexiaDyspepsiaHeavinessWeakness

Subjects feel weak & get easily exhausted

Wet Beriberi :- Cardiovascular manifestations are prominent- Edema of legs, face, trunk & serous cavities are more prominent- Palpitation, Breathlessness &

distended neck veins are observed- Death occurs due to heart failure

Dry Beriberi:- CNS manifestations are major features- Walking becomes difficult- Peripheral Neuritis with sensory disturbance leads to complete paralysis

Infantile Beriberi :- Occurs in infants born to mothers

suffering from Thiamine deficiency- Restlessness & Sleeplessness are

observed

Wrist & foot drop:Dry Beri Beri

Edema:Wet Beri Beri

Wernicke – Korsakoff syndrome :- It is also called Cerebral Beriberi- Clinical features are Encephalopathy (Ophthalmoplegia, Nystagmus,Cerebellar Ataxia) + Psychosis

Polyneuritis :- Common in chronic Alcoholics- Alcohol inhibits intestinal absorption of Thiamine- It may also be associated with Pregnancy & old age- Result is increased concentration of pyruvate & lactate, leading to acidosis

RiboflavinInvolved in energy metabolism; part of two

co-enzymes, FMN and FADParticipate in citric acid cycle and beta

oxidation and electron transportRemove ammonia during deamination of

some amino acidsAssociated with antioxidant glutathione

peroxidase

Causes of Riboflavin Deficiency

It is synthesised by intestinal flora ; therefore, deficiency is uncommon.

Riboflavin deficiency usually accompanies other deficiency diseases such as Beriberi, Pellagra and Kwashiorkar

Manifestations of Riboflavin Deficiency

i. Glossitisii. Magenta coloured tongueiii. Cheilosisiv. Angular stomatitisv. Circumcorneal vascularisationvi. Proliferation of the bulbar conjuctival

capillaries

Glossitis & Magenta coloured tongue

Cheilosis

Angular stomatitis

Circumcorneal vascularisation

Dermatitis

Niacin (Nicotinic Acid)Made from tryptophan; essential nutrient if

protein intake is inadequate60 mg tryptophan converts to 1 mg niacinNiacin is converted to NAD+ & NADP+NAD and NADP play key role in oxidation-

reduction reactionsCoenzyme component that participates in

over 200 metabolic reactions

Causes of Niacin Deficiency

Dietary deficiency of Tryptophan :- Maize : Niacin is in bound form ; therefore unavailable- Sorghum : Contains Leucine. Leucine inhibits QPRTase enzyme & thus conversion of Niacin to NAD+

Deficient synthesis : - Conversion of Tryptophan to Niacin is not possible in Pyridoxal deficiency

Isoniazid : Inhibits Pyridoxal phosphate formation & thus formation of NAD+

Hartnup Disease :- Tryptophan absorption from intestine is defective

Carcinoid Syndrome :Tryptophan is unavailable as it is used by tumour cells

Niacin Deficiency / Pellagra

Pellagra means “Rough Skin”It is seen more in women. May be because

Tryptophan metabolism is inhibited by estrogen metabolites

Symptoms are :- Dermatitis- Diarhhea- Dementia

Dermatitis : - Early stages - bright red erythema occurs- Increased pigmentation around neck – Casal’s Necklace

Diarrhea :- May lead to weight loss, Nausea & Vomiting

Dementia:- Seen in chronic diseases- Irritability , inability to concentrate & poor memory are seen in mild cases- Ataxia & spasticity are also seen

Dermatitis