Trace element : Zinc

Zinc deficiency is marked by an eczematoid rash either diffusely or in intertriginous areas. A microcytic anemia can develop from a lack of copper and glucose intolerance and may be associated with a lack of chromium. Daily administration of trace metal supplements obviates these problems.

Prostate REF: Trace element analysis in biological specimens by R. F. M. Herber, Markus Stoeppler page 551

9.4 mg/day REF: Ganong’s 22^nd ed p. 314

Dose of zinc for acrodermatitis enteropathica is 2-3 mg/kg body weight

Alcohol dehydrogenase [Ref: Chatterje Shinde Biochemistery 6/e p551]

Zinc containing enzymes are:

1)  Superoxide dismutase (it is a Cu-Zn protein complex)

2)  Carbonic anhydrase

3)  Leucine amino peptidase

4)  Carboxy peptides ‘A’

5)  Alcohol dehydrogenase

6)  Retinine reductase

7)  Alkaline phosphatase

8)  Glutamate dehydrogenase

9)  Lactate dehydrogenase

10)    DNA and RNA polymerase

11)    d-ALA dehydratase

Zinc

Acrodermatitis enteropathica (AE):

• It is an autosomal recessive disorder of zinc absorption.
• It presents in infancy, characterized by a triad of acral dermatitis (face, hands, feet, anogenital area), alopecia, and diarrhea.
• These infants have a defect in an intestinal zinc transporter, the human ZIP4 protein encoded on the SLC39A4 gene. 
• Mutations in this gene prevents appropriate enteral zinc absorption.
• AE classically presents during infancy on weaning from breast milk to formula or cereal, which have lower zinc bioavailability than breast milk.

Zinc treatment in wilson disease:

• It is efficient in Wilson’s disease 
• Nontoxic
• Produces a negative copper balance by blocking intestinal absorption of copper
• It induces hepatic metallothionein synthesis, which sequesters additional toxic copper

Acrodermatitis enteropathica is a rare autosomal recessive disorder caused by an inability to absorb sufficient zinc from diet.

The cutaneous eruption consists of vesicio-bullous, eczematous, dry scaly or psoriasisiform skin lesions symmetrically distributed in body. Associated manifestations include chronic, stomatitis, glossitis, paronychia and superinfection with candida albicans.

Zinc supplement given during an acute diarrhoea episode reduces severity and duration of disease.

WHO and UNICEF recommend that children 6 months be given 20 mg daily.

The recommended duration for treatment is for 10 to 14 days.

Ref: Park 21st edition, page 204.

Protein–DNA interactions are regulated by several motifs which includes Helix turn–Helix motif, Zinc finger motif and Leucine Zipper motif.

Note: Zinc is absolutely required for normal spermatogenesis, fetal growth, and embryonic development.

Zinc is also an integral component of many metalloenzymes. It is involved in the synthesis and stabilization of proteins, DNA, and RNA and plays a structural role in ribosomes and membranes.

Copper plays an important role in iron metabolism, melanin synthesis, energy production, neurotransmitter synthesis, CNS function, the synthesis and cross-linking of elastin and collagen and the scavenging of superoxide radicals

Ref: Russell R.M., Suter P.M. (2012). Chapter 74. Vitamin and Trace Mineral Deficiency and Excess. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

Zn is an essential component of several enzymes like carbonic anhydrase, alcohol dehydrogenase, alkaline phosphatase, carboxypeptidase and superoxaide dismutase.

Daily requirement of Zinc for adult men is 9.4mg/d and for women is 6.8mg/d.

• RDA for zinc in males and females are 11mg and 8mg.
• RDA for Zinc during pregnancy is 11mg/d 
• Zinc recommendation for lactating women is 12mg/d.
• Features of zinc deficiency in children are growth retardation, skeletal abnormalities, poor wound healing, diarrhea, skin rash and delayed sexual maturation.

Prostate contributes 20% of the total volume of the semen. Secretion from the prostate contains the following:

• Spermine
• Citric acid
• Cholesterol, phospholipids
• Fibrinolysin, fibrinogenase
• Zinc
• Acid phosphatase

• Fructose
• Phosphorylcholine
• Ergothioneine
• Ascorbic acid
• Flavins
• Prostaglandins

Ans. is ‘a’ i.e., Zinc

o Paneth cells are zinc-containing cells widely distributed in Lieberkuhn’s crypts of intestine in a variety of species. o These cells have atypically orietned bright eosinophilic granules containing a variety of antimicroial proteins and play a role in mucosal immunity (and not mucin secretion).

o The principle defense molecule secreted by Paneth cells are alpha-defensins.

o In addition to defensins, Paneth cells secrete lysozyme, TNF-a, and phospholipase-A2.

C i.e. Zinc

C i.e. Zinc

Ans. is All

Hypogonadism (sexual infantilism, loss of libido), poor weight gain (growth retardation) and poor wound healing are seen in zinc deficiency.

Ans. is ‘d’ i.e., 20 mg/10-14 days

According to WHO guidlines

Dose of Zinc

2 month – 6 month = 10 mg / day x 14 days > 6 months = 20 mg/day x 14 days

Ans. is ‘c’ i.e., Zinc

Ans. is ‘c’ i.e., Zinc

A i.e. Zinc

Ans: C i.e. Zinc

Manifestations of Zinc deficiency

• Primary T-cell lymphocyte immune system dysfunction (leading to failure to terminate incipient malignancies, viral and fungal infections);
• Frequent opportunistic infections (due to inability to protect cell membranes from viruses, toxins, complement, and venoms);
• Respiratory and skin allergies,
• Asthma;
• Chronic diarrhea;
• Abnormal neurosensory changes,
• Poor appetite (particularly in the young and aged);
• Mental lethargy,
• Fertility problems (including hypogonads, failure of sexual maturity, benign prostatitis in men, and menstrual cramping and bloating in women),
• Birth defects;
• Growth failure (dwarfism) and growth retardation;
• Premature aging;
• Vision problems;
• Loss of taste;
• Joint pain;
• Essential hypertension;
• Angina pectoris;
• Ischemia of effort;
• Delayed wound healing;
• Scleroderma;
• Systemic scleroderma (including lethal pulmonary hypertension);
• Loss of hair color;
• Anemia;
• Striae (stretch marks);
• Night blindness;
• Acne; and
• Defective connective tissue and macular degeneration; and
• Apathy and irritability.

Ans. D i.e. None

Ans. B: Triad of diarrhea, dementia and dermatitis

Acrodermatitis enteropathica is a rare inherited form of zinc deficiency, characterized by:

• Periorificial and Acral Dermatitis
• Alopecia
• Diarrhea

Symptoms of Zinc Deficiency

• Poor Immune system
• Weight loss
• Intercurrent infections
• Hypogonadism in males
• Lack of sexual development in females
• Growth retardation
• Dwarfism
• Delayed puberty in adolescents
• Rough skin
• Poor appetite
• Mental lethargy
• Delayed wound healing
• Short stature
• Diarrhea

One easily recognized sign which may be caused by zinc deficiency is white spots, bands, or lines on fingernails (leukonychia).

Some women may have multiple parallel white bands or lines on the fingernails marking menstrual cycles when marginal zinc deficiency was present.

Ans. B: Coagulation Pathway

Severe maternal zinc deficiency has been associated with congenital malformations or spontaneous abortions Zinc deficiency has been reported to result in sexual infantilism (zinc is required for proper reproduction) Zinc is required for wound healing. Zinc enhances cell growth and division.

Zinc

• Zinc is found in nearly 100 specific enzymes, serves as structural ions in transcription factors and is stored and transferred in metallothioneins.
• It is “typically the second most abundant transition metal in organisms” after iron and it is the only metal which appears in all enzyme classes.
• In proteins, Zn ions are often coordinated to the amino acid side chains of aspartic acid, glutamic acid, cysteine and histidine.
• There are 2-4 grams of zinc distributed throughout the human body.
• Most zinc is in the brain, muscle, bones, kidney, and liver, with the highest concentrations in the prostate and parts of the eye.
• Semen is particularly rich in zinc, which is a key factor in prostate gland function and reproductive organ growth.
• In humans, zinc plays “ubiquitous biological roles”.
• It interacts with “a wide range of organic ligands”, and has roles in the metabolism of RNA and DNA, signal transduction, and gene expression.
• It also regulates apoptosis.
• In the brain, zinc is stored in specific synaptic vesicles by glutamatergic neurons and can “modulate brain excitability”.
• It plays a key role in synaptic plasticity and so in learning.
• However it has been called “the brain’s dark horse” since it also can be a neurotoxin, suggesting zinc homeostasis plays a critical role in normal functioning of the brain and central nervous system.
• Zinc is an efficient Lewis acid, making it a useful catalytic agent in hydroxylation and other enzymatic reactions.
• The metal also has a flexible coordination geometry, which allows proteins using it to rapidly shift conformations to perform biological reactions.
• Two examples of zinc-containing enzymes are carbonic anhydrase and carboxypeptidase, which are vital to the processes of carbon dioxide (CO2) regulation and digestion of proteins, respectively.

Ans. Zinc

Ans. is ‘c’ i.e., 6-8 mg