Author: Neelam Maurya

Vitamin B3- metabolism

Vitamin B3- metabolism

Q. 1

Niacin is required for growth of – Oxidase

 A

M. tuberculosis

 B

M. kansasii

 C

M. Scrofuloderma

 D

M. Avium

Q. 1

Niacin is required for growth of – Oxidase

 A

M. tuberculosis

 B

M. kansasii

 C

M. Scrofuloderma

 D

M. Avium

Ans. A

Explanation:

Ans. is ‘a’ i.e., M. tuberculosis 


Q. 2

One mg. of Niacin is produced by…………………….. mg. of Tryptophan-

 A

22

 B

37

 C

55

 D

60

Q. 2

One mg. of Niacin is produced by…………………….. mg. of Tryptophan-

 A

22

 B

37

 C

55

 D

60

Ans. D

Explanation:

Ans. is ‘d’ i.e., 60 

About 60 mg of tryptophan is required to result in I mg of niacin.


Q. 3

Niacin is synthesized from ‑

 A

Arginine

 B

Histidine

 C

Tryptophan

 D

Tyrosine

Q. 3

Niacin is synthesized from ‑

 A

Arginine

 B

Histidine

 C

Tryptophan

 D

Tyrosine

Ans. C

Explanation:

Q. 4

Niacin is derived from which amino acid?

 A

Tyrosine

 B

Phenylalanine

 C

Tryptophan

 D

Methionine

Q. 4

Niacin is derived from which amino acid?

 A

Tyrosine

 B

Phenylalanine

 C

Tryptophan

 D

Methionine

Ans. C

Explanation:

Quiz In Between



Vitamin B3- metabolism

Vitamin B3- metabolism


VITAMIN B3 (NIACIN)

  • Vitamin B3 is also called as Nicotinic acid or nicotinamide.
  • Niacin can be synthesized tryptophan (1mg of the niacin formed from 60mg of tryptophan)

Active form of niacin-

  1. NAD+ (Nicotinamide Adenine Dinucleotide)
  2. NADP+ (Nicotinamide Adenine Dinucleotide Phosphate)

Coenzymes involved in reactions-

  1. Oxidoreduction reaction-

i) NAD+ linked dehydrogenases-

  • Isocitrate dehydrogenase
  • Malate dehydrogenase
  • α-ketoglutarate dehydrogenase
  • glutamate dehydrogenase
  • glyceraldehydes-3- P dehydrogenase
  • lactate dehydrogenase
  • β-hydroxyl acyl CoA dehydrogenase

ii) NADP+ linked dehydrogenases-

  • Glucose-6-P dehydrogenase in HMP shunt pathway

 2. ADP ribosylation

Metabolism & Excretions-

  • Nicotinamide excreted in urine are N1 –methyl nicotinamide and N1 –methyl 2-pyridone 5-carboxamide (2-pyridine).
  • N-methyl nicotinamide metabolized to methylpyridone-2- and 4-carboxamide
  • Nicotinic acid conjugated with glycine to form nicotinuric acid
  • Nicotinic acid methylated to trignonelline.
  • Daily recommended dose – 20mg/day 

Exam Important

  1. Vitamin B3 is also called as Nicotinic acid or nicotinamide.
  2. Niacin can be synthesized tryptophan (1mg of the niacin formed from 60mg of tryptophan)

Coenzymes involved in reactions-

  1. Oxidoreduction reaction-

i) NAD+ linked dehydrogenases-

  • Isocitrate dehydrogenase
  • Malate dehydrogenase
  • α-ketoglutarate dehydrogenase
  • glutamate dehydrogenase
  • glyceraldehydes-3- P dehydrogenase
  • lactate dehydrogenase
  • β-hydroxyl acyl CoA dehydrogenase

ii) NADP+ linked dehydrogenases-

  • Glucose-6-P dehydrogenase in HMP shunt pathway
  • Nicotinamide excreted in urine are N1 –methyl nicotinamide and N1 –methyl 2-pyridone 5-carboxamide (2-pyridine).
  • N-methyl nicotinamide metabolized to methylpyridone-2- and 4-carboxamide
  • Nicotinic acid conjugated with glycine to form nicotinuric acid
  • Nicotinic acid methylated to trignonelline.
  • Daily recommended dose – 20mg/day
Don’t Forget to Solve all the previous Year Question asked on Vitamin B3- metabolism

Module Below Start Quiz

Vitamin B3 Deficiency

Vitamin B3 & Deficiency

Q. 1

Nicotinamide is preferred over Niacin because?

 A Flushing is seen with niacin
 B

Abdominal pain is seen with niacin

 C Breathlessness is seen with niacin
 D

Less bioavailability

Q. 1

Nicotinamide is preferred over Niacin because?

 A Flushing is seen with niacin
 B

Abdominal pain is seen with niacin

 C Breathlessness is seen with niacin
 D

Less bioavailability

Ans. A

Explanation:

Flushing is seen with niacin REF: Nutrition Almanac by John D. Kirschmann, Nutrition Search, Inc page 31

Niacin causes sudden release of histamine which produces certain s/e which are not seen with nicotinamide

  • Intense flushing
  • Tingling
  • Numbness
  • Throbbing headache due to cerebral vasodilation.

Q. 2

A 54-year-old man has a total cholesterol of 272 and LDL level of 210. His therapy is initiated with dietary modification and an exercise regimen, but he is unresponsive and so is prescribed nicotinic acid (Niacin). Which of the following symptoms will this patient likely experience from this drug?

 A

Bradycardia

 B

Facial flushing

 C

Hypoalbuminemia

 D

Hypoglycemia

Q. 2

A 54-year-old man has a total cholesterol of 272 and LDL level of 210. His therapy is initiated with dietary modification and an exercise regimen, but he is unresponsive and so is prescribed nicotinic acid (Niacin). Which of the following symptoms will this patient likely experience from this drug?

 A

Bradycardia

 B

Facial flushing

 C

Hypoalbuminemia

 D

Hypoglycemia

Ans. B

Explanation:

Niacin, or vitamin B3, is an agent that results in the following physiologic changes: LDL reductions tend to occur in 5-7 days with the maximal effect seen in 3-5 weeks; triglycerides and VLDL are reduced by 20% to 40% in 1-4 days; and HDL levels can increase by 20%.

This agent is indicated as adjunctive therapy in patients with elevated cholesterol and triglycerides when diet and other nondrug therapies are inadequate. 

The most common adverse effect of this agent is generalized flushing with a sensation of warmth, especially in the facial area.

This reaction may be so severe in some patients that they discontinue therapy.

Other common adverse effects include hepatotoxicity, tachycardia, hypoalbuminemia, hyperglycemia, nausea, vomiting, hyperuricemia, glucose intolerance, pruritus, peptic ulcer disease, and dry skin.


Q. 3

Maize contains the vitamin niacin. Pellagra is a disease that results from niacin deficiency.

Assertion: Consumption of maize may aggravate Pellagra.

Reason: Some strains of maize contains excess of Leucine which interferes in the conversion of Tryptophan into Niacin.

 A

Both Assertion and Reason are true, and Reason is the correct explanation for Assertion

 B

Both Assertion and Reason are true, and Reason is not the correct explanation for Assertion

 C

Assertion is true, but Reason is false

 D

Assertion is false, but Reason is true

Q. 3

Maize contains the vitamin niacin. Pellagra is a disease that results from niacin deficiency.

Assertion: Consumption of maize may aggravate Pellagra.

Reason: Some strains of maize contains excess of Leucine which interferes in the conversion of Tryptophan into Niacin.

 A

Both Assertion and Reason are true, and Reason is the correct explanation for Assertion

 B

Both Assertion and Reason are true, and Reason is not the correct explanation for Assertion

 C

Assertion is true, but Reason is false

 D

Assertion is false, but Reason is true

Ans. A

Explanation:

Pellagra is caused by Niacin deficiency and anything that interferes in the absorption or production of Niacin will aggravate the condition.

Ref: Park’s Textbook of Preventive Medicine, 17th Edition, Page 427.

Quiz In Between


Q. 4

A 10 year old child is suspected of having pellagra because of chronic symptoms including diarrhea, a red scaly rash, and mild cerebellar ataxia. However, his diet is not deficient in protein and he appears to be ingesting adequate amounts of niacin. A sister has a similar problem. Chemical analysis of his urine demonstrates large amounts of free amino acids. Which of the following is the most likely diagnosis?

 A

Alkaptonuria

 B

Carcinoid syndrome

 C

Ehlers-Danlos syndrome

 D

Hartnup’s disease

Q. 4

A 10 year old child is suspected of having pellagra because of chronic symptoms including diarrhea, a red scaly rash, and mild cerebellar ataxia. However, his diet is not deficient in protein and he appears to be ingesting adequate amounts of niacin. A sister has a similar problem. Chemical analysis of his urine demonstrates large amounts of free amino acids. Which of the following is the most likely diagnosis?

 A

Alkaptonuria

 B

Carcinoid syndrome

 C

Ehlers-Danlos syndrome

 D

Hartnup’s disease

Ans. D

Explanation:

The child has Hartnup’s disease.
This condition clinically resembles pellagra (“diarrhea, dementia, and dermatitis”), and may be misdiagnosed as this nutritional (niacin) deficiency. In fact, niacin therapy may actually be helpful in controlling the symptoms.
The underlying problem is a defect in the epithelial transport of neutral amino acids, including tryptophan, which can act as a precursor of niacin. The defective amino acid transport leads to poor absorption of dietary amino acids as well as excess amino acid secretion in the urine.
Alkaptonuria  is characterized by urine that turns black upon standing and a debilitating arthritis.
 
Carcinoid syndrome is seen in patients with carcinoid tumor. It is characterized by episodes of flushing, diarrhea, hypertension, and bronchoconstriction.
 
Ehlers-Danlos syndrome is a disease characterized by abnormal collagen formation leading to very elastic skin, joint problems, and fragility of some blood vessels and the intestines.
 
Ref: Bender D.A. (2011). Chapter 44. Micronutrients: Vitamins & Minerals. In D.A. Bender, K.M. Botham, P.A. Weil, P.J. Kennelly, R.K. Murray, V.W. Rodwell (Eds),Harper’s Illustrated Biochemistry, 29e.

Q. 5

In Niacin deficiency, all of the following are seen except:

 A

Deafness

 B

Diarrhea

 C

Dementia

 D

Dermatitis

Q. 5

In Niacin deficiency, all of the following are seen except:

 A

Deafness

 B

Diarrhea

 C

Dementia

 D

Dermatitis

Ans. A

Explanation:

Ans. is ‘a’ i.e., Deafness 

o Niacin deficiency results in ‘Pellagra’

Pellagra is identified by the presence of three ‘D’s —> Diarrhea, Dementia, Dermatitis


Q. 6

Niacin deficiency causes all except –

 A

Diarrhea

 B

Dyspepsia

 C

Dementia

 D

Dermatitis

Q. 6

Niacin deficiency causes all except –

 A

Diarrhea

 B

Dyspepsia

 C

Dementia

 D

Dermatitis

Ans. B

Explanation:

Ans. is ‘b’ i.e., Dyspepsia 

Quiz In Between


Q. 7

Niacin deficiency cause –

 A

Pellagra

 B

Scurvy

 C

Rickets

 D

Lathyrism

Q. 7

Niacin deficiency cause –

 A

Pellagra

 B

Scurvy

 C

Rickets

 D

Lathyrism

Ans. A

Explanation:

Ans. is ‘a’ i.e., Pellagra 


Q. 8

Niacin deficiency in a maize-eating population is due to-

 A

High Tryptophan 

 B

High lsoleucine

 C

High leucine

 D

High Phenylalanine

Q. 8

Niacin deficiency in a maize-eating population is due to-

 A

High Tryptophan 

 B

High lsoleucine

 C

High leucine

 D

High Phenylalanine

Ans. C

Explanation:

Ans. is ‘c’ i.e., High Leucine 

Excess of Leucine interferes in conversion of Tryptophan into Niacin, and aggravates the pallagrogenic action of inake.


Q. 9

Niacin deficiency causes ‑

 A

Pigmentation

 B

Diarrhea

 C

Rash

 D

Lactic acidosis

Q. 9

Niacin deficiency causes ‑

 A

Pigmentation

 B

Diarrhea

 C

Rash

 D

Lactic acidosis

Ans. B

Explanation:

Ans. is ‘b’ i.e., Diarrhea 

  • Deficiency of niacin (and tryptophan) causes pellagra which is characterized by 3 Ds, i.e. dermatitis, diarrhea and dementia.
  • Pellagra is common in people consuming maize and sorghum (jowar) as their staple foods.
  • These two are poor in niacin and tryptophan, and rich in leucin.
  • Excess of leucine inhibits the conversion of tryptophan into niacin.

Quiz In Between



Vitamin B3 Deficiency

Vitamin B3 Deficiency


Uses-

  • As lipid modifying drug
  • Reduces triglyceride and LDL-C levels

Vitamin B3 Deficiency-

Pellagra-

  • Caused due to niacin deficiency
  • Common in people consuming maize and sorghum (poor in niacin & tryptophan and rich in leucine)

Clinical Manifestations-

Characterized by 4Ds-

            Dermatitis, Diarrhea, Dementia and Death

  • Casal’s necklace– rash form around neck
  • Apathy
  • Depressive psychosis
  • Hartnup disease
  • Carcinoid syndrome

Vitamin B3 Toxcity-

  • Cutaneous flushing
  • Gastric irritation
  • Hepatic toxicity
  • Macular edema and cysts
  • Hyperuricemia
  • Glucose intolerance

Exam Important

Pellagra-

  • Caused due to niacin deficiency
  • Common in people consuming maize and sorghum (poor in niacin & tryptophan and rich in leucine)

Clinical Manifestations-

Characterized by 4Ds-

  • Dermatitis, Diarrhea, Dementia and Death
  •  Casal’s necklace– rash form around neck
Don’t Forget to Solve all the previous Year Question asked on Vitamin B3 Deficiency

Module Below Start Quiz

Lipoprotein Structure

Lipoprotein- structure

Q. 1 The major lipid of the lipoproteins is:
 A Oleic acid
 B Palmitic acid
 C Linoleic acid
 D Arachidonic acid
Q. 1 The major lipid of the lipoproteins is:
 A Oleic acid
 B Palmitic acid
 C Linoleic acid
 D Arachidonic acid
Ans. D

Explanation:

Arachidonic acid


Q. 2

Human plasma lipoprotein containing the highest percentage of triacylglycerol by weight is:

 A

VLDL

 B

Chylomicrons

 C

HDL

 D

LDL

Q. 2

Human plasma lipoprotein containing the highest percentage of triacylglycerol by weight is:

 A

VLDL

 B

Chylomicrons

 C

HDL

 D

LDL

Ans. B

Explanation:

Triacylglycerol or triglyceride is an ester that is derived from glycerol and three fatty acids. Chylomicrons are lipoproteins that are lowest in density and largest in size which contains the highest percentage of triacylglycerol and the smallest percentage of protein.

Besides containing 80 to 95 percent triglyceride, chylomicrons contain 2 to 7 percent cholesterol, 3 to 6 percent phospholipid, and 1-2 percent protein.
 
Ref: Lippincott’s Illustrated Reviews: Biochemistry, 3rd Edition, Page 225; Fitness and Health By Brian J. Sharkey, Steven E. Gaskill, 2007, Page 274.

Q. 3

. The human plasma lipoprotein containing the highest percentage of triacylglycerol by weight is:

 A

VLDL

 B

Chylomicrons

 C

HDL

 D

LDL

Q. 3

. The human plasma lipoprotein containing the highest percentage of triacylglycerol by weight is:

 A

VLDL

 B

Chylomicrons

 C

HDL

 D

LDL

Ans. B

Explanation:

B i.e. Chylomicrins

Lipoproteins may be differentiated on the basis of their lipid & protein compositions. The lipoproteins containing the largest percentage of triacylglycerol are Chylomicrons (90%).

Lipoprotein Structure



Lipoprotein Structure

Lipoprotein Structure


LIPOPROTEINS

  • Free fatty acids (FAA) is metabolically most active of the plasma lipids.
  • Lipids are transported in the form of lipoproteins.
  • Non polar lipid contains cholesterol ester, cholesterol, phospholipid, triacylglycerol.
  • Protein part of lipoprotein is apolipoprotein.

Major lipoproteins according to density are-

  1. Chylomicrons- These are principal form in which dietary lipids (exogenous lipids) are carried from intestine to liver.
  2. Very low density lipoproteins (VLDL)
  3. Low density lipoproteins (LDL)- major source of cholesterol to peripheral tissues.
  4. Intermediate density lipoproteins (IDL)
  5. High density lipoproteins (HDL)

Separation of Lipoproteins-

  1. Electrophoresis-
  • Chylomicrons have no mobility and remains at orginial position
  • HDL has maximum mobility and move longest distance.

2. Ultracentrifugation-

  • Chylomicrons are largest with maximum lipid contents.

Exam Important

  • Free fatty acids (FAA) is metabolically most active of the plasma lipids.
  • Non polar lipid contains cholesterol ester, cholesterol, phospholipid, triacylglycerol.
  • Protein part of lipoprotein is apolipoprotein.
  • Chylomicrons- These are principal form in which dietary lipids (exogenous lipids) are carried from intestine to liver.
  • Low density lipoproteins (LDL)- major source of cholesterol to peripheral tissues.

Electrophoresis-

  • Chylomicrons have no mobility and remains at orginial position
  • HDL has maximum mobility and move longest distance.

Ultracentrifugation-

  • Chylomicrons are largest with maximum lipid contents.
Don’t Forget to Solve all the previous Year Question asked on Lipoprotein Structure

Module Below Start Quiz

Bile acid synthesis

Bile Acid Synthesis

Q. 1

Secondary bile acids are synthesised by:

 A

Liver

 B

Intestine

 C

Both liver and intestine

 D

Pancreas

Q. 1

Secondary bile acids are synthesised by:

 A

Liver

 B

Intestine

 C

Both liver and intestine

 D

Pancreas

Ans. B

Explanation:

Bile acids are synthesized in the liver.

Bile acids are divided into primary or secondary: Primary bile acids are synthesized in the liver and secondary bile acids are synthesized from primary bile acids in the intestine by colonic bacteria. 
Ref: Harrison, E-18, P-2461.

Q. 2

The four major bile acids found in humans are synthesized from:

 A

Cholesterol

 B

Amino acids

 C

Bilirubin

 D

Protein

Q. 2

The four major bile acids found in humans are synthesized from:

 A

Cholesterol

 B

Amino acids

 C

Bilirubin

 D

Protein

Ans. A

Explanation:

When considering bile as a digestive secretion, it is the bile acids that represent the most important components. They are synthesized from cholesterol and secreted into the bile conjugated to glycine or taurine, a derivative of cysteine. 

Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 25. Overview of Gastrointestinal Function & Regulation. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong’s Review of Medical Physiology, 24e.

Q. 3

Bile acid synthesized in liver (primary bile acids) is:

 A

Lithocholic acid

 B

Cholic acid

 C

Deoxycholic acid

 D

All of the above

Q. 3

Bile acid synthesized in liver (primary bile acids) is:

 A

Lithocholic acid

 B

Cholic acid

 C

Deoxycholic acid

 D

All of the above

Ans. B

Explanation:

 

Bile acids

  • They are steroid acids found predominantly in the bile.
  • Bile acid refers to the protonated (-COOH) form.
  • ile salt refers to the deprotonated or ionized (-COO-) form.
  • Bile salts are bile acids compounded with a cation, usually sodium.
  • The salts of taurocholic acid and glycocholic acid (derivatives of cholic acid) represent approximately eighty percent of all bile salts.
  • The two primary bile acids are cholic acid, and chenodeoxycholic acid.
  • Bile acids, glycine and taurine conjugates, and 7-alpha-dehydroxylated derivatives (deoxycholic acid and lithocholic acid) are all found in intestinal bile.
  • The increase in bile flow is exhibited with an increased secretion of bile acids.
  • e main function of bile acid is to facilitate the formation of micelles, which promotes processing of dietary fat
  • Bile acids are made in the liver by the cytochrome P450-mediated oxidation of cholesterol.
  • They are conjugated with taurine or the amino acid glycine, or with a sulfate or a glucuronide, and are then stored in the gallbladder, which concentrates the salts by removing the water.
  • Rate limiting step is the addition of a hydroxyl group on position 7 of the steroid nucleus by the enzyme cholesterol 7 alpha-hydroxylase.
  • Upon eating a meal, the contents of the gallbladder are secreted into the intestine, where bile acids serve the purpose of emulsifying dietary fats.
  • Bile acids serve other functions, including eliminating cholesterl from the body, drivin the ow of bile to eliminabte catabolites from the liver, emulsifying lipids and fat soluble vitamins in the intestine g to form micelles thatt. can be transported via the lacteal system, and aiding in the reduction of the bacteria flora found in the smal intes ine a biliary tract.

Conjugated bile acids are more efficient at emulsifying fats because at intestinal pH, they are more ionized than unconjugated bile acs.

  • The body produces about 800 mg of cholesterol per day and about half of that is used for bile acid synthesis.
  • In total about 20-30 grams of bile acids are secreted into the intestine daily.

About 90% of excreted bile acids are reabsorbed by active transport in theileum and recycled in what is referred to as the enterohepatic circulation which moves the bile salts from the intestinal system back to the liver and the gallbladder.


Q. 4

Bile acids are reabsorbed from ‑

 A

Duodenum

 B

Proximal jejunum

 C

Distal jejunum

 D

Ileum

Q. 4

Bile acids are reabsorbed from ‑

 A

Duodenum

 B

Proximal jejunum

 C

Distal jejunum

 D

Ileum

Ans. D

Explanation:

Ans. is ‘d’ i.e., Ileum

Quiz In Between


Q. 5

Bile acids are synthesized from ‑

 A

Heme

 B

Cholesterol

 C

Ribulose

 D

Arachidonic acid

Q. 5

Bile acids are synthesized from ‑

 A

Heme

 B

Cholesterol

 C

Ribulose

 D

Arachidonic acid

Ans. B

Explanation:

Ans. is ‘b’ i.e., Cholesterol

  • Primary bile acids are cholic acid and chenodeoxycholic acid, which are synthesized from cholesterol in liver.
  • In the intestine some of the primary bile acids are converted into secondary bile acids, i.e., deoxycholic acid (formed from cholic acid) and lithocholic acid (derived from chenodexoxycholic acid).
  • Glycine and taurine conjugates of these bile acids are called as bile salts.
  • For example, cholic acid is a bile acid, and its glycine conjugate (glycocholic acid) is a bile salt.
  • Bile salts help in digestion and absorption of fat by emulsification and micelles formation.
  • Bile salts act as detergents, i.e., they have surface tension lowering action.
  • Detergent action is due to amphipathic nature of bile salts (Note : Amphipathic molecules are molecules that contain both hydrophobic non-polar as well as hydrophilic-polar ends).



Q. 6

Rate limiting enzyme in bile acid synthesis ‑

 A

Desmolase

 B

21 α-hydroxylase

 C

7α-hydroxylase

 D

12α-hydroxylase

Q. 6

Rate limiting enzyme in bile acid synthesis ‑

 A

Desmolase

 B

21 α-hydroxylase

 C

7α-hydroxylase

 D

12α-hydroxylase

Ans. C

Explanation:

Ans. is ‘c’ i.e., 7α-hydroxylase

About half of the cholesterol in the body is ultimately metabolized to bile acids.

The primary bile acids are synthesized from cholesterol in liver. These are cholic acid and chenodeoxycholic acid.

Rate limiting enzyme in primary bile acids synthesis is 7α – hydroxylase (cholesterol 7α – hydroxylase).

This enzyme is inhibited by bile acids and induced by cholesterol.

Thyroid hormones induce transcription of 7a-hydroxylase, thus in patients with hypothyroidism plasma cholesterol tends to rise (because of inhibition of 7α-hydroxylase which in turn inhibits conversion of cholesterol to bile acids).


Q. 7

Which of the following is/are bile acids?

 A

Cholic acid

 B

Lithocholic acid

 C

Deoxycholic acid

 D

All of the above

Q. 7

Which of the following is/are bile acids?

 A

Cholic acid

 B

Lithocholic acid

 C

Deoxycholic acid

 D

All of the above

Ans. D

Explanation:

 

Primary bile acids are cholic acid and chenodeoxycholic acid, which are synthesized from cholesterol in liver. In the intestine some of the primary bile acids are converted into secondary bile acids, i.e., deoxycholic acid (formed from cholic acid) and lithocholic acid (derived from chenodexoxycholic acid).

  • Glycine and taurine conjugates of these bile acids are called as bile salts. For example, cholic acid is a bile acid, and its glycine conjugate (glycocholic acid) is a bile salt.
  • Bile salts = Sodium or potassium + Amino acid (glycine or taurine) + Bile acids (Cholic acid or chenodeoxycholic acid)
  • So, Bile salts are : –
  • Sodium + glycine + cholic acid = Sodium-glyco-cholic acid (sodium-glyco-cholate)
  • Sodium + taurine + cholic acid = Sodium-tauro-cholic acid (Sodium-tauro-cholate)
  • Sodium + glycine + chenodeoxycholic aicd = Sodium-glyco-chenodeoxycholate
  • Sodium + taurine + chenodeoxycholic acid = Sodium-tauro-chenodeoxycholate o Similarly potassiun bile salts are potassium-glycocholate, potassium-taurocholate, potassium-glyco­chenodexoxycholate, and potassium-tauro-chenodexoxycholate.

Q. 8

Primary bile acid is‑

 A

Deoxycholic acid

 B

Lithocholic acid

 C

Chenodeoxycholic acid

 D

None

Q. 8

Primary bile acid is‑

 A

Deoxycholic acid

 B

Lithocholic acid

 C

Chenodeoxycholic acid

 D

None

Ans. C

Explanation:

Ans. is ‘c’ i.e., Chenodeoxycholic acid 

  • Primary bile acids are cholic acid and chenodeoxycholic acid, which are synthesized from cholesterol in liver. In the intestine some of the primary bile acids are converted into secondary bile acids, i.e., deoxycholic acid (formed from cholic acid) and lithocholic acid (derived from chenodexoxycholic acid).
  • Glycine and taurine conjugates of these bile acids are called as bile salts. For example, cholic acid is a bile acid, and its glycine conjugate (glycocholic acid) is a bile salt.

Quiz In Between



Bile acid synthesis

Bile acid synthesis


BILE ACID SYNTHESIS

  • The primary bile acids are produced from cholesterol in liver.

Primary bile acids are-

  1. Cholic acid
  2. Chenodexycholic acid
  3. glycocholic acid, glycochenodeoxycholic acid, taurocholic acid.
  • Secondary bile acids produced from cholesterol in intestine.

Secondary bile acids are-

  1. Deoxycholic Acid
  2. Lithocholic Acid
  • Cholesterol converted to 7 Hydrocholesterol by 7 α- Hydroxylase.
  • The first and rate limiting step by enzyme 7 α- Hydroxylase.

Exam Important

  • The primary bile acids are produced from cholesterol in liver.

Primary bile acids are-

  1. Cholic acid
  2. Chenodexycholic acid
  3. Glycocholic acid, glycochenodeoxycholic acid, taurocholic acid.
  • Secondary bile acids produced from cholesterol in intestine.

Secondary bile acids are-

  1. Deoxycholic Acid
  2. Lithocholic Acid
  • Cholesterol converted to 7 Hydrocholesterol by 7 α- Hydroxylase.
  • The first and rate limiting step by enzyme 7 α- Hydroxylase.
Don’t Forget to Solve all the previous Year Question asked on Bile acid synthesis

Module Below Start Quiz

Hemochromatosis

Hemochromatosis

Q. 1

MOST common mutation seen in heriditary hemochromatosis is:

 A

C282Y

 B

H63D

 C

TFR2

 D

SLC11A3

Q. 1

MOST common mutation seen in heriditary hemochromatosis is:

 A

C282Y

 B

H63D

 C

TFR2

 D

SLC11A3

Ans. A

Explanation:

The most common mutation in hereditary hemochromatos is a homozygous G to A mutation resulting in a cysteine to tyrosine substitution at position 282 (C282Y). Another relatively common  mutation (H63D) results in a substitution of histidine to aspartic acid at codon 63.

Mutations like  transferrin receptor 2 TFR2 mutation and  ferroportin 1 gene, SLC11A3 mutation are rare.

Ref: Harrisons principles of internal medicine, 18th edition, Page: 3162


Q. 2

Which of the following condition is not true about Hemochromatosis?

 A

Hypogonadism

 B

Arthropathy

 C

Diabetes mellitus

 D

Desferrioxamine is treatment of choice

Q. 2

Which of the following condition is not true about Hemochromatosis?

 A

Hypogonadism

 B

Arthropathy

 C

Diabetes mellitus

 D

Desferrioxamine is treatment of choice

Ans. D

Explanation:

Phlebotomy is the treatment of choice of hemochromatosis. Chelating agent desferrioxamine is indicated when anemia or hypoproteinemia is severe enough to preclude phlebotomy.

Hemochromatosis is a common inherited disorder of iron metabolism in which dysregulation of intestinal iron absorption results in deposition of excessive amounts of iron in parenchymal cells resulting in tissue damage and organ dysfunction.

Liver is the first organ to be affected and hepatomegaly is seen in more than 95% of patients. Diabetes mellitus occur in 65% of patients with advanced disease. Arthropathy is seen in 20-25% of symptomatic patients. Second and third metacarpophalangeal joints are the first joints to be involved.

Manifestations of hypogonadism includes loss of libido, impotence, amenorrhea, testicular atrophy and gynecomastia. Most common cardiac manifestation is congestive heart failure.


Q. 3

Hemochromatosis is a defect in metabolism of

 A

Iron

 B

Copper

 C

Magnesium

 D

Calcium

Q. 3

Hemochromatosis is a defect in metabolism of

 A

Iron

 B

Copper

 C

Magnesium

 D

Calcium

Ans. A

Explanation:

Ans. is `a’ i.e., Iron

o Hemochromatosis is characterized by the excessive accumulation of body iron, most of which is deposited in parenchymal organs such as the liver and pancreas.

Quiz In Between


Q. 4

The first test to become positive in patients with Hemochromatosis is:

 A

Increased Serum Iron

 B

Increased Serum Ferritin

 C

Increased Transferrin Saturation

 D

Increased Liver Enzymes

Q. 4

The first test to become positive in patients with Hemochromatosis is:

 A

Increased Serum Iron

 B

Increased Serum Ferritin

 C

Increased Transferrin Saturation

 D

Increased Liver Enzymes

Ans. C

Explanation:

Answer is C (Increased Transferrin Saturation):

Transferrin Saturation is the first blood test to become elevated in Hemochromatosis.

The first biochemical manifestation of hemochromatosis is an increase of transferring saturation, which reflects an uncontrolled influx of iron into the blood stream .from enterocytes and macrophages.

The serum transferrin saturation and serum ferritin levels are the two most important indicators of hemochromatosis and body iron stores.

Elevation of transferrin levels precedes elevation offerritin levels.

The first biochemical manifestation of hetnochromatosis is an increase in serum transferrin saturation.

Serum iron concentration per se is not a good indicator for iron overload states like Hemochromatosis.

Liver Enzymes may be normal or elevated depending on the extent of hepatocyte damage.

They are usually normal or only mildly elevated in the early stages of hemochromatosis.

Laboratory findings in Hemochromatosis

Transferrin saturation is the first blood test to become elevated in hemochromatosis homozygotes

The sensitivity of elevated transferring saturation to identify a patient with hemochromatosis is 94 to 98% and its specificity is 70 to 98%.

Transferrin saturation is usually > 60% in symptomatic men and >50% in symptomatic women

  • Unbound
  • Serum
  • Liver

DNA testing by polymerase chain reaction may he used to detect mutations of the HFE gene.


Q. 5

All of the following statements about hereditary hemochromatosis are true Except

 A

Arthropathy involving small joints of hands may be seen

 B

Skin pigmentation is a frequent presentation

 C

Desferroxamine is the treatment of choice

 D

Hypogonadism may be seen

Q. 5

All of the following statements about hereditary hemochromatosis are true Except

 A

Arthropathy involving small joints of hands may be seen

 B

Skin pigmentation is a frequent presentation

 C

Desferroxamine is the treatment of choice

 D

Hypogonadism may be seen

Ans. C

Explanation:

Answer is C (Desferroxamine is the treatment of choice):

The therapy of hematochromatosis involves removal of excess body iron Iron removal is best acieved by periodic phlebotomies which is the treatment of choice for Hematochromosis.

Chelating agents like desferoxamine are less effective and indicated when anemia or hypoproteinemia is severe enough to preclude phlebotomy (Harrison.

Chelatingagents are not the treatment of choice for Hematochromatosis.


Q. 6

All are seen in hemochromatosis except‑

 A

Hypogonadism

 B

Arthropathy

 C

Bronze diabetes

 D

Desferrioxamine is the treatment of choice

Q. 6

All are seen in hemochromatosis except‑

 A

Hypogonadism

 B

Arthropathy

 C

Bronze diabetes

 D

Desferrioxamine is the treatment of choice

Ans. D

Explanation:

Answer is D (Desferrioxamine is the treatment of choice):

The treatment of choice for Hematochromatosis is removed of excess body iron by Phlebotomy and not with the use of chelating agents like desfernoxamine.

Removal of Excessive Body iron

  • Phlebotomy is the treatment of choice  Iron removal is best accomplished by once or twice weekly phlebotomy of 500m1,

– These should be continued until the serum ferritin level is < 50pg/L (May be required for 1-2 years)

– Thereafter phlebotomies are performed at appropriate intervals to maintain ferritin levels between 50-100 tg/L (usually one phlebotomy every 3 months)

  • Chelating agents (such as Desferoxamine) are alternative agents and indicated when anemia and hypoproteinemia are severe enough to preclude phlebotomy

Treatment of Haematochromatosis

Phlebotomy is the treatment of choice in Hematochromatosis

Therapy of Haematochromatosis involves removal of excessive body iron and supportive treatment of damaged organs

Alcohol consumption should he eleminatedQ as increases ruck hematochronhth,sLs ten /oh/ Arthropathv,

Hypogonadism, Diabetes and Bronzing (pigmentation) of skin are all characteristic manifestation of hematochromatosis

Note: The combination of skin hyperpigmentation and insulin deficiency (diabetes) is called Bronze diabetes.

The characterstic  clinical features of Haemoehromatosis in order frequency areQ :

  • Hepatomegaly (95%1
  • Skin pigmentation (90%)
  • Diabetes mellitus (65%)
  • Arthropathy (25-50%)
  • Cardiac disease (15%)
  • Hypogonadism

Quiz In Between


Q. 7

Which of the following statements about Hemochromatosis is true:

 A

Shows complete penetrance

 B

Inherited as an autosomal recessive disorder

 C

Phlebotomy is curative

 D

More common in Females

Q. 7

Which of the following statements about Hemochromatosis is true:

 A

Shows complete penetrance

 B

Inherited as an autosomal recessive disorder

 C

Phlebotomy is curative

 D

More common in Females

Ans. B

Explanation:

Answer is B (Inherited as an Autosomal Recessive) :

Hereditary Hemochromatosis is essentially inherited us an autosomal recessive condition.

Hereditary Hemochromatosis is essentially an Autosomal Recessive condition

The most common form of hereditary hemochromatosis is related to mutations in HFE gene, which is a gene located on the short arm of chromosome 6 and is FILA linked

HFE related hereditary hemochromatosis (most common type) is inherited as an autosomal recessive condition

Hereditary Hemochromatosis shows incomplete penetrance

Incomplete penetrance refers to the lack of disease symptoms in an individual despite the presence of pathological gene mutation

Expression of Hemochromatosis is variable and many HFE positive people neither have nor develop disease, thus displaying the phenomenon of incomplete penetrance

This suggests that other genetic and / or environmental factors modify the pathogenesis of disease Hereditary Hemochromatosis is more common in Men

The clinical expression of disease is 5 –10 times more common in men than women – Harrison Phlebotomy is an effective management option but it does not lead to cure

The therapy of hemochromatosis involves removal of excess body iron which is best accomplished by phlebotomy Phlebotomy is not curative and will be required at appropriate intervals to maintain.ferritin levels (usually one phlebotomy every 3 months)’ – Harrison


Q. 8

What accumulates in tissues in hemochromatosis‑

 A

Iron

 B

Copper

 C

Ceruloplasmin

 D

Lipofuschhin

Q. 8

What accumulates in tissues in hemochromatosis‑

 A

Iron

 B

Copper

 C

Ceruloplasmin

 D

Lipofuschhin

Ans. A

Explanation:

Ans. is ‘a’ i.e., Iron

  • Hemochromatosis is characterized by the excessive accumulation of body iron, most of which is deposited in parenchymal organs such as liver and pancreas.
  • Hemochromatosis is a disorder of iron metabolism.
  • Characterized by a triad of :-
  • Micronodular cirrhosis
  1. Diabetes mellitus
  2. Skin pigmentation
  • Organ not showing iron deposition in hemochromatosis
  1. Testis

Q. 9

In hemochromatosis iron not deposited in ‑

 A

Heart

 B

Pituitary

 C

Testis

 D

Skin

Q. 9

In hemochromatosis iron not deposited in ‑

 A

Heart

 B

Pituitary

 C

Testis

 D

Skin

Ans. C

Explanation:

Ans. is ‘c’ i.e., Testis

In hemochromatosis, hypogonadism is caused by impairment of hypothalamic pituitary function and not due to deposition of Iron in the Testis.

Hemochromatosis

  • Hemochromatosis is characterized by the excessive accumulation of body iron, most of which is deposited in parenchymal organs such as liver and pancreas.
  • The total body content of the iron is tightly regulated, as the daily losses are matched by gastrointestinal absorption. In hereditary hemochromatosis, regulation of intestinal absorption of dietary iron is lost, leading to net iron accumulation of 0.5 to 1.0 gm/year.
  • It may be recalled that the total body iron pool ranges from 2-6 gm in normal adults; about 0.5 gm is stored in the liver 98% of which is hepatocytes. In hemochromatosis the iron accumulation may exceed 50 gm, over one third of which accumulates in the liver.
  • The iron accumulation is life long, the rate of net iron accumulation is 0.5 to 1.0 gm/year. The disease manifests itself typically after 20 gm of storage iron have accumulated. The disease first mainfests itself in the fifth to sixth decades of life.
  • Excessive iron is directly toxic to host tissues
  • The clinical features of hemochromatosis are characterized principally by deposition of excess iron in the following organs in decreasing order of severity.

Quiz In Between



Hemochromatosis

Hemochromatosis


HEMOCHROMATOSIS

  • Hemochromatosis is a common inherited disorder of iron metabolism leading to deposition of excessive amount of iron in parenchymal cells leading to fibrosis and organ failure.
  • The iron storage pigment in tissues is called as hemosiderin (least in skin).
  • Hemosiderosis is an acquired condition.
  • Liver is the first organ to be affected & maximum deposition of iron by hemochromatosis.
  • Classic triad is- cirrhosis, diabetes mellitus, skin pigmentation.

Conditions of Iron Overload States– classified as

I) Herediatry- hemochromatosis

II) Acquired overload-

a) Iron loading-

  1. Thalassemia major
  2. Sideroblastic anaemia
  3. Chronic haemolytic anaemia

IRON POISONING

  • Ingestion of a number of ferrous sulphate tablets may cause acute iron poisoning.
  • Clinical features : Severe vomiting ,Diarrhea ,GI bleeding ,there may be severe shock, hepatic & renal failure
  • Antidotes:Desferrioxamine is given parenterally (IM or IV), whereas deferiprone and deferasirox are used orally.

Exam Important

  • The iron storage pigment in tissues is called as hemosiderin (least in skin).
  • Hemosiderosis is an acquired condition.
  • Liver is the first organ to be affected & maximum deposition of iron by hemochromatosis.
  • Conditions of Iron Overload States– classified as

I)Herediatry- hemochromatosis

  • Iron loading-
  1. Thalassemia major
  2. Sideroblastic anaemia
  3. Chronic haemolytic anaemia
  • Antidotes for iron poisoning:Desferrioxamine is given parenterally (IM or IV), whereas deferiprone and deferasirox are used orally.
Don’t Forget to Solve all the previous Year Question asked on Hemochromatosis

Module Below Start Quiz

Malcare WordPress Security