Tag: Module

Metabolism of HDL

Metabolism of HDL


HDL METABOLISM

  • Nascent HDL is synthesized and secreted from intestine and liver.
  • Nascent HDL contain phospholipids, cholesterol and Apo A.
  • Lecithin cholesterol Acyl Transferase (LCAT) esterified by cholesterol.
  • Apo- A- I activates LCAT.

Cholesterol is transported to liver in 2 ways-

  1. Indirect pathway Cholestryl ester is transferred from HDL to VLDL and chylomicrons by cholestryl ester transfer protein (CETP)à Liver
  2. Direct pathway HDL cholesterol by liver via scavenger receptors.
  • HDL particles are referred to as scavangers.
  • The level of HDL in serum is inversely related to the incidence of MI.
  • HDL is cardioprotective and anti- atherogenic is referred to good cholesterol.
  • HDL- Cholesterol appears to be the best independent predictor of coronary artery disease.
  • HDL collects excess cholesterol iron tissues and transport it to liver and steroidogenic tissues. This is called Reverse cholesterol transport.

Exam Important

  • Nascent HDL is synthesized and secreted from intestine and liver.
  • Nascent HDL contain phospholipids, cholesterol and Apo A.
  • Lecithin cholesterol Acyl Transferase (LCAT) esterified by cholesterol.
  • Apo- A- I activates LCAT.

Cholesterol is transported to liver in 2 ways-

  1. Indirect pathwayCholestryl ester is transferred from HDL to VLDL and chylomicrons by cholestryl ester transfer protein (CETP)à Liver
  2. Direct pathway– HDL cholesterol by liver via scavenger receptors.
  • HDL particles are referred to as scavangers.
  • The level of HDL in serum is inversely related to the incidence of MI.
  • HDL is cardioprotective and anti- atherogenic is referred to good cholesterol.
  • HDL- Cholesterol appears to be the best independent predictor of coronary artery disease.
  • HDL collects excess cholesterol iron tissues and transport it to liver and steroidogenic tissues. This is called Reverse cholesterol transport.
Don’t Forget to Solve all the previous Year Question asked on Metabolism of HDL

Module Below Start Quiz

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


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


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

Glycolipids

GLYCOLIPIDS


GLYCOLIPIDS (GLYCOSPHINGOLIPIDS)

  • Glycosphingolipid = Sphingosine + long chain fatty acid + sugars
  • Glycolipids are synthesized in endoplasmic reticulum.
  • Glycosphingolipids are 4 types-

Cerebrosides– ( ceramide + monosaccharides)

  • Cerebroside= sphingoside + long chain fatty acid + glucose
  • Monosaccharides used is mostly glucose (glucocerebroside) or galactose (galactocerebroside).
  • Clinical Aspect- 
  1. Krabbe’s disease caused by deficiency of enzyme of ?- galactosidase (Galactocerebroside accumulates in brain).
  2. Gaucher’s disease caused by deficiency of ?- glucosidase (glucocerebrosidase)
  • Glucocerebroside (glucosylceramide) is accumulated in brain.
  1. Sulfatides– cerebroside + sulphate
  2. Globosides– ceramide + oligosaccharide
  3. Gangliosides
  • ceramide + oligosaccharide chain (glucose+galactose) + N- acetylneuromic acid (NANA)
  • Gangliosides= Sphingosine+ long chain fatty acid + oligosaccharide chain (glucose or galactose)+ NANA
  • Clinical Aspect-
  • Tay- Sach’s Disease– caused due to deficiency of hexosaminidase (alpha subunit)
  • Sandoff disease- caused due to deficiency of hexoaminidase (Beta subunit)

Exam Important

  • Glycosphingolipid = Sphingosine + long chain fatty acid + sugars
  • Glycolipids are synthesized in endoplasmic reticulum.
  • Glycosphingolipids are 4 types-

Cerebrosides– ( ceramide + monosaccharides)

  • Cerebroside= sphingoside + long chain fatty acid + glucose
  • Monosaccharides used is mostly glucose (glucocerebroside) or galactose (galactocerebroside).
  • Clinical Aspect-
  1. Krabbe’s disease caused by deficiency of enzyme of ?- galactosidase.
  2. Galactocerebroside accumulates in brain.
  3. Gaucher’s disease caused by deficiency of ?- glucosidase (glucocerebrosidase)
  4. Glucocerebroside (glucosylceramide) is accumulated in brain.
  5. Sulfatides– cerebroside + sulphate
  6. Globosides– ceramide + oligosaccharide
  7. Gangliosides
  • ceramide + oligosaccharide chain (glucose+galactose) + N- acetylneuromic acid (NANA)
  • Gangliosides= Sphingosine+ long chain fatty acid + oligosaccharide chain (glucose or galactose)+ NANA
  • Tay- Sach’s Disease– caused due to deficiency of hexosaminidase (alpha subunit) .
Don’t Forget to Solve all the previous Year Question asked on GLYCOLIPIDS

Module Below Start Quiz

Isoenzymes

ISOENZYMES


ISOENZYMES (ISOZYMES)

  • Isoenzymes are the physically distinct forms of the same enzyme.
  • Isoenzymes differ from each other structurally, electrophoretically and immunologically.
  • Isoenzymes possess quaternary structure and are made up of two or three different subunit (mutimeric).
  • Isoenzymes catalyze the same reaction and act on same substrate, but with different Km and Vmax values i.e. isozymes have different kinetics.

Plasma Enzymes-

  • Functional plasma enzymes- specific function in the plasma. E.g. Coagulation factors (thrombin), lipoprotein lipase, clotting factors.
  • Non functional enzymes- E.g. alkaline phosphatase, acid phosphatase, gamma glutamyl transpeptidase, LDH, Creatine kinase.

Lactate Dehydrogenase (LDH)

  • LDH with two subunits- H(heart) and M(muscle)
  • It has five isoenzymes.
Name of the isoenzyme Tissue location
LDH-1 Heart muscle
LDH-2 RBC
LDH-3 Brain
LDH-4 Liver and skeletal muscle
LDH-5 Liver and skeletal muscle
  • In MI, LDH1 is raised more than LDH2.
  • Normal LDH pattern on electrophoresis is LDH2 > LDHI > LDH 3 > LDH 4>LDH5
  • Increased in LDH level- pancreatitis.

Creatine Kinase (CK)

  • Three isoenzymes.
  • It is subunit M(myocardium) and B (Brain).
Name of isoenzyme Tissue localisation
CK-1 Brain
CK-2 Heart
CK-3 Skeletal Muscle

Alkaline Phosphatase (ALP)-

Isoenzyme Tissue Location
Alpha-1 ALP Epithelial cells of biliary canaculi
Alpha-2 heat liable ALP Hepatic cells
Alpha-2 heat stable ALP Placenta (Inhibited by Phenylalanine)
Pre beta ALP Osteoblast
Gamma ALP Intestinal cells
Leukocyte ALP Leukocytes
  • Raised activity of alkaline phosphatase is useful in diagnosis of bone and liver pathology.

 Transaminase-

  • Aspartate Transaminase- increase in myocardium.
  • Mitochondrial isoenzyme present in liver.
  • Alanine Transaminase (ALT)-  mainly in liver and entirely in Cytoplasm. 

Protease-

  • Serine Proteasesserine residue at the active site(serine, histidine, aspirate).
  • E.g.- Trypsin, chymotrypsin, elastase (catalytic traid)
  • Inhibited by disopropylphosphofluridate binds covalently to serine residue.
  • Activated in intestine by proteolytic activation.

Carboxyl or acid Proteases-

  • Most important carboxyl proteases is Pepsin.

Exam Important

  1. Isoenzymes differ from each other structurally, electrophoretically and immunologically.
  2. Isoenzymes possess quaternary structure and are made up of two or three different subunit (mutimeric).
  3. Functional plasma enzymes- specific function in the plasma.- E.g. Coagulation factors (thrombin), lipoprotein lipase, clotting factors.
  4. Non functional enzymes  E.g. alkaline phosphatase, acid phosphatase, gamma glutamyl transpeptidase, LDH, Creatine kinase.
  5.  LDH has five isoenzymes.
Name of the isoenzyme Tissue location
LDH-1 Heart muscle
LDH-2 RBC
LDH-3 Brain
LDH-4 Liver and skeletal muscle
LDH-5 Liver and skeletal muscle

 6. In MI, LDH1 is raised more than LDH2.

 7. Creatine Kinase (CK)- Three isoenzymes.

CK-1 Brain
CK-2 Heart

 8. ALP found in liver, bone, kidney, intestinal mucosa and placenta.

9. Serine Proteasesserine residue at the active site(serine, histidine, aspirate).

10. Serine proteases- E.g.- Trypsin, chymotrypsin, elastase (Catalytic triad).

11. Serine proteases activated in intestine by proteolytic activation.

12.  Most important carboxyl proteases is Pepsin.

Don’t Forget to Solve all the previous Year Question asked on ISOENZYMES

Module Below Start Quiz

Histones

HISTONES


Histones

  • Most abundant chromatin Protein.
  • Histones are divided into-
  1. Core Histone
  2. Linker Histone
  • 5 classes- H1, H2A, H2B (Lysine), H3 and H4 (arginine).
  • Linker histone- is loosely bound to nucleosome.
  • Modifications-
  1. Acetylation of H3 & H4
  2. Acetylation of histones associated with chromosomal assembly during DNA replication.
  3. Phosphorylation of H1 is associated with condensation of chromosome during replication.
  4. Methylation correlated with activation or repression of gene transcription.
  • Chromatins are of two types-
  • Euchromatin- Transcriptionally active chromatin and is uncondensed. Chromatins are less stained.
  • Heterochromatin- Transcriptionally inactive, chromatin stains densely, chromatin densely packed. 2 types-
  1.  Constitutive- seen in centromere and chromosomal ends of the telomere.
  2.  Facultative
  • Chromosomes-
  •  In humans, there are 23 pairs of chromosomes.
  •  The position of centromere is the characteristic mark for specific chromosome.
  •  The centromere is AT rich region.
  • Total number of chromosome in humans is 46 (23 pairs).
  • The number of base pairs in haploid set of chromosome is 3.0 x 1O9 (3 billion bp)
  • Percentage of exons in human genome is approximately 1.14% (1.5-2%)
  • The number of protein coding genes in human genome is 20,687.
  • The genes account for 10-15% of DNA.

Exam Important

  • Total number of chromosome in humans is 46 (23 pairs).
  • The number of base pairs in haploid set of chromosome is 3.0 x 1O9 (3 billion bp)
  • Percentage of exons in human genome is approximately 1.14% (1.5-2%)
  • The number of protein coding genes in human genome is 20,687.
  • The genes account for 10-15% of DNA.
  • Euchromatin is transcriptionally active and heterochromatin is transcriptionally inactive.
  • For euchromatin, chromatin is less densely packed.
  • For heterochromatin, chromatin is densely packed.
Don’t Forget to Solve all the previous Year Question asked on HISTONES

Module Below Start Quiz

Organization of DNA in the cell

ORGANIZATION OF DNA IN THE CELL


Organization of DNA in the cell 

  • Genome in the prokaryotes is loosely packed.
  • In eukaryotes, DNA is well organized inside the nucleus.
  • Levels of organization of DNA is– DNA Double helix
  •  Nucleosomes form of chromatin are of-

10nm chromatin fibril

  • In eukaryotics, Nucleosomes are  separated   by spacer DNA to which histone H1 is attached This continuous string of nucleosomes, representing beads-on-a string form of chromatin is termed as 10 nm fiber.
  • DNA double helix is wrapped nearly twice (exactly 1.75 times) over   a histone octamer in left-handed helix to form a disk like structure.

30nm chromatin fibril–  (Solenoid)

  • Groups of nucleosome form’DNA fibril’
  • 6 such DNA fibrils form 30 nm chromatin fibril.
  • The double stranded DNA wraps twice around a histones.
  • A nucleosome associated with histone H1 is called chromatosome.
  • A series of nucleosome (beads on a string) is called as polynucelosome or chromatin.
  • DNA molecule is amphipathic.
  • At physiological pH, DNA is negatively charged (Acidic).

Exam Important

  • Chromatin is unfolded and uncondensed.
  • Chromatin and chromosome are made up of DNA and non-histone proteins.
  • At the physiological pH, DNA is negatively charged because of phosphate group.
  • DNA molecule is an amphipathic.
Don’t Forget to Solve all the previous Year Question asked on ORGANIZATION OF DNA IN THE CELL

Module Below Start Quiz

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

Metabolism Of Purine

METABOLISM OF PURINE


METABOLISM OF PURINE

  • Purine nucleotides are synthesized-
  1. Adenosine monophosphate (AMP)
  2. Guanosine monophosphate (GMP)
  • Purine nucleotides synthesized by 2 pathways-
  1. De novo synthesis
  2. Salvage pathway

De novo synthesis

  • It is synthesis in liver.
  • It takes place in cytoplasm.
  • Precursors for de novo synthesis are –
  1. Glycine provides C4, C5 and N7
  2. Aspartate provides N1
  3. Glutamine provides N3 and N9
  4. Tetrahydrofolate derivatives furnish C2 and C8
  5. Carbon dioxide provides C6
  • IMP (also called inosinic acid) is the first purine nucleotide, which is synthesized as the precursor of AMP (also called adenylic acid) and GMP (also called guanylic acid).
  • The enzyme PRPP glutamyl amidotransferase is controlled by feedback inhibition of nucleotides.
  • The rate limiting step of de novo Purine Synthesis is PRPP Glutamyl amidotransferase.

Salvage pathway-

  • Free purine bases (adenine, guanine and hypoxanthine) and purine nucleosides are formed in cells during the metabolic degradation of nucleic acids and nucleotides. These free purine           bases and purine nucleosides are reused in the formation of purine nucleotides. This is called salvage pathway

Catabolism of Purine Metabolism- (Degradation)

  • Adenine nucleotides catabolism- liver, heart muscle, Skeletal muscle, GIT mucosa
  • Guanine nucleotides catabolism- liver, spleen, kidney, pancreas, GIT mucosa.
  • Human catabolises purine to uric acid.
  • First metabolic product of purines is Xanthine.
  • In higher primates, Allantoin by enzyme uricase is the end product.

Disorders of Purine Metabolism-

  • Gout
  • Lesch- Nyhan Syndrome
  • Adenosine deaminase deficiency
  • Purine nucleoside phophorylase deficiency

Exam Important

  • First Nucleotide formed in Purine Synthesis-lnosine Mono Phosphate (lMP)
  • Liver is the major site of nucleotide biosynthesis.
  • Tissues which cannot synthesis purine nucleotides by de nevo pathway are- brain, erythrocytes and leuckocytes.
Don’t Forget to Solve all the previous Year Question asked on METABOLISM OF PURINE

Module Below Start Quiz

Malcare WordPress Security