Methionine metabolism
Activation of methionine and transmethylation
Conversion of methionine to cysteine
Degradation of cysteine.
Cysteine metabolism
Formation
Metabolic Function
Metabolism Disorders of Sulfur containing amino acid
As an essential amino acid, methionine is not synthesized de novo in humans and other animals, which must ingest methionine or methionine-containing proteins. In plants and microorganisms, methionine biosynthesis belongs to the aspartate family, along with threonine and lysine (via diaminopimelate, but not via α-aminoadipate). The main backbone is derived from aspartic acid, while the sulfur may come from cysteine, methanethiol, or hydrogen sulfide.
Methionine is an amino acid( a building block of protein) hence cannot be produced by the body but only supplied by the diet.Although mammals cannot synthesize methionine, they can still use it in a variety of biochemical pathways: Metabolism,Regeneration, Reverse-transulfurylation pathway: conversion to cysteine & Ethylene synthesis.
ONE OF THESE ABOVE , ONLY METABOLISM IS DISCUSSED.
S containing AA Metabolism Met, Cys-Methionine, cysteine, homocysteine, and ...ivvalashaker1
Methionine, cysteine, homocysteine, and taurine are the 4 common sulfur-containing amino acids, but only the first 2 are incorporated into proteins. Sulfur belongs to the same group in the periodic table as oxygen but is much less electronegative
As an essential amino acid, methionine is not synthesized de novo in humans and other animals, which must ingest methionine or methionine-containing proteins. In plants and microorganisms, methionine biosynthesis belongs to the aspartate family, along with threonine and lysine (via diaminopimelate, but not via α-aminoadipate). The main backbone is derived from aspartic acid, while the sulfur may come from cysteine, methanethiol, or hydrogen sulfide.
Methionine is an amino acid( a building block of protein) hence cannot be produced by the body but only supplied by the diet.Although mammals cannot synthesize methionine, they can still use it in a variety of biochemical pathways: Metabolism,Regeneration, Reverse-transulfurylation pathway: conversion to cysteine & Ethylene synthesis.
ONE OF THESE ABOVE , ONLY METABOLISM IS DISCUSSED.
S containing AA Metabolism Met, Cys-Methionine, cysteine, homocysteine, and ...ivvalashaker1
Methionine, cysteine, homocysteine, and taurine are the 4 common sulfur-containing amino acids, but only the first 2 are incorporated into proteins. Sulfur belongs to the same group in the periodic table as oxygen but is much less electronegative
Fate of Glucogenic and Ketogenic amino acid
Amino acid are the currency of of nitrogen and protein economy of the host, hence they are used in many pathways beyond protein synthesis, including energy production and neurotransmitter synthesis.
All amino acid are comprised of an amino group and a carbon skeleton. During metabolism these two parts are separated as they have different ‘fates’
Of the liberated amino acid approximately 75% are utilized while remainder serve as precursors for important biological compound and those not utilized are degraded to amphibolic intermediates
The pathway of amino acid catabolism is quite similar in most organism
This PPT is on Amino acid metabolism. And the topics covered under this ppt are Transamination, deamination
Book referred: https://www.amazon.in/Biochemistry-2019-Satyanarayana-Satyanarayana-Author/dp/B07WGHCTKZ/ref=sr_1_1?dchild=1&qid=1591608419&refinements=p_27%3AU+Satyanarayana&s=books&sr=1-1
designed for undergraduate level teaching of nitrogen metabolism focusing on amino acid metabolism in biochemistry. this is third in the series of three lectures. ideal for MBBS level teaching
Amino Acid Metabolism for MBBS, Laboratory Medicine.pptxRajendra Dev Bhatt
All tissues have some capability for synthesis of the non-essential amino acids, amino acid remodeling, and conversion of non-amino acid carbon skeletons into amino acids and other derivatives that contain nitrogen.
However, the liver is the major site of nitrogen metabolism in the body.
In times of dietary surplus, the potentially toxic nitrogen of amino acids is eliminated via transaminations, deamination, and urea formation.
Similar to Sulfur containing amino acid metabolism (20)
a brief on thyroid gland covering following titles:
Introduction
Anatomy and physiology of thyroid gland
Synthesis of thyroid hormones
Regulation
Mechanism of action
Biological function
MI is one of the CVS complication leading to mortality whose diagnosis is mainly dependent on clinical presentation and other supportive investigation. clinical laboratory plays crucial role in its diagnosis, prognosis and monitoring therapy.
introduction of Purine and Pyrimidine metabolism, biosynthesis and degradation of nucleotides, biological functions and metabolic disorders, chemical analogues and therapeutic drugs, uric acid metabolism
Triacylglycerol and compound lipid metabolismDipesh Tamrakar
Biosynthesis and metabolic regulation of triglyceride and other compound lipids: glycerophospholipids, sphingophospholipids, ether glycerolipids and glycolipids
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
2. Methionine metabolism
A. Activation of methionine and transmethylation
B. Conversion of methionine to cysteine
C. Degradation of cysteine.
Cysteine metabolism
A. Formation
B. Metabolic Function
Metabolism Disorders of Sulfur containing amino
acid
2
3. It is sulfur-containing, essential, glucogenic amino
acid.
Forms succinyl CoA
It is required for the initiation of protein biosynthesis.
Degradation of methionine results in the synthesis of
cysteine and cystine.
Metabolism of sulfur-containing amino acids may be
studied under the following major headings:
A. Activation of methionine and transmethylation
B. Conversion of methionine to cysteine
C. Degradation of cysteine.
3
4. 1. ACTIVATION OF
METHIONINE TO SAM In the major pathway, methionine is activated to
‘active methionine’ or S-adenosyl methionine (SAM).
The synthesis of S-adnosylmethionine occurs by the
transfer of an adenosyl group from ATP to sulfur
atom of methionine.
This is done by the enzyme, methionine adenosyl
transferase (MAT).
There are 3 isoenzymes for MAT, out of which 1 and 3
are of hepatic origin.
SAM is the main source of methyl groups in the body.
The activation of methionine is unique as the sulfur
becomes a sulfonium atom by addition of 3 Carbon
3ATP are consumed in the formation SAM.
4
5. 2. Methyl Transfer:
In methionine, the thio-ether linkage (C–S–C) is
very stable.
In SAM, due to the presence of a high energy bond,
the methyl group is labile, and may be transferred
easily to other acceptors
SAM transfer methyl group to acceptor and gets
itself converted to SAH
3. Homocysteine:
S-adenosyl homocysteine (SAH) is hydrolyzed to
homocysteine and adenine, which is the higher
homologue of cysteine
5
6. 4. Methionine synthesis:
Homocysteine can be converted to methionine by
addition of a methyl group.
This methyl group is donated from one-carbon pool
with the help of vitamin B12.
5. Homocysteine degradation:
Homocysteine condenses with serine to form
cystathionine.
This is catalyzed by pyridoxal phosphate dependent
cystathionine-beta synthase.
Absence of this enzyme leads to homocystinuria.
6
7. 6. Cysteine synthesis:
In the next step, cystathionine is hydrolyzed by
cystathionase to form cysteine and homoserine.
Net result is that the SH group from methionine is
transferred to serine to form cysteine.
This is called trans-sulfuration reaction
7. Final oxidation:
Homoserine is deaminated and then decarboxylated
to propionyl CoA.
It finally enters into the TCA cycle as succinyl CoA,
which is converted to glucose.
7
9. METHIONINE IN
TRANSMETHYLATION
REACTIONS
Many compounds become functionally active after
methylation
Protein methylation helps to control protein turnover
and protects from immediate degration
In Plants, SAM is the precursor for the synthesis of a
plant hormone, ethylene ( for growth and development)
Some important products are:
1. Creatine
2. Epinephrine
3. Choline
4. Melatonin
9
10. These reactions are called methyl transfer reactions,
and these are carried out with the help of S-adenosyl
methionine (SAM).
Methyl groups are originally derived from the one
carbon pool.
The methyl-THFA can transfer the methyl group to
homocysteine.
Vitamin B12 is the co-enzyme for the reaction.
This would account for the deficiency of folic acid
associated with B12 deficiency (folate trap).
SAM is the methyl donor for all the transmethylation
reactions.
10
11. Hypermethioninemias
Causes of hypermethioninemia are:
1. Impaired utilization
2. Excessive remethylation of homocysteine
3. Secondary to hepatic dysfunction.
Oasthouse syndrome is due to malabsorption of
methionine.
Such children excrete methionine, aromatic amino
acids and branched chain amino acids in urine.
11
12. It is non-essential and glucogenic.
Cysteine is present in large quantity in keratin of
hair and nails.
Formation of Cysteine is by using the carbon
skeleton contributed by serine and sulfur
originating from methionine.
Methionine → SAM → SAH → Homocysteine →
Cystathionine → Cysteine
This sulfur containing amino acid undergoes
desulfurization to yield pyruvate.
12
14. DEGRADATION OF
CYSTEINE
1. Transamination:
Cysteine is transaminated to form beta mercapto
pyruvic acid and finally pyruvate.
The beta mercapto pyruvate can transfer the S to
CN to form thiocyanate (SCN).
14
15. 2. The sulfur may be removed either as H2S or
elemental sulfur or as sulfite.
3. Cysteine on decarboxylation gives beta
mercaptoethanolamine.
This is used for synthesis of co-enzyme A .
15
16. METABOLIC FUNCTION OF
CYSTEINE
Formation of Glutathione:
Glutathione is gamma glutamyl cysteinyl glycine
Glutathione is generally abbreviated as GSH, to indicate
the reactive SH group.
It was isolated in 1921 by Sir Frederick Hopkins (Nobel
prize, 1929).
1. Glutamate + Cysteine → gamma glutamyl cysteine
2. Glutamyl cysteine + glycine → glutathione
Both steps need hydrolysis of each ATP.
16
18. Co-enzyme Role:
Metabolic role of GSH is mainly in reduction reactions
2GSH → GS-SG + H2
(Reduced) (Oxidized)
The hydrogen released is used for reducing other
substrates.
A few examples are shown below:
i. Maleylacetoacetate → fumarylacetoacetate
ii. Cysteic acid → taurine
iii. (Iodine) I2 + 2GSH → 2HI + GS-SG
18
19. RBC Membrane Integrity:
Glutathione is present in the RBCs.
This is used for inactivation of free radicals formed
inside RBC.
The enzyme is glutathione peroxidase, a selenium
containing enzyme.
The glutathione is regenerated by an NADPH
dependent glutathione reductase.
The NADPH is derived from the glucose- 6-phosphate
(GPD) shunt pathway.
The occurrence of hemolysis in GPD deficiency is
attributed to the decreased regeneration of reduced
glutathione
19
21. Met-hemoglobin:
The met-Hb is unavailable for oxygen transport.
Glutathione is necessary for the reduction of met-
hemoglobin (ferric state) to normal Hb (ferrous
state).
2Met-Hb-(Fe3+) + 2GSH → 2Hb-(Fe2+) + 2H+ +GS-
SG
21
22. Conjugation for Detoxification:
Glutathione helps to detoxify several compounds by
transferring the cysteinyl group, e.g.
a. organophosphorus compounds
b. halogenated compounds
c. nitrogenous substances (chlorodinitrobenzene)
d. heavy metals
e. drug metabolism.
The reaction is catalyzed by glutathione-S-transferase
(GST)
22
23. GST is seen in all tissues,especially in liver.
GST is a dimer; and each chain may beany one out
of 4 polypeptides; so there are 6 iso-enzymes.
These are named as A, B, C, D, E and AA. Moreover,
many polymorphic forms of GST are also described.
23
24. Activation of Enzymes:
Many enzymes having SH groups in the active site are
kept in the active form by the glutathione.
Such enzymes are active in the reduced form.
Glutathione keeps the enzymes in reduced, active state.
Formation of Taurine:
Cysteine is oxidized to cysteic acid and then
decarboxylated to form taurine.
Alternatively cysteine is oxidized to cysteine sulfinic
acid.
It is then decarboxylated by a decarboxylase to
hypotaurine which in turn is oxidized to taurine.
Taurine is used for conjugation of bile acids.
24
26. Taurine + Cholyl CoA → Taurocholate + CoA-SH
Taurine is a modulator of calcium fluxes, calcium
binding and movement.
In the CNS it is an inhibitory neurotransmitter.
Taurine is widely distributed in animal tissues.
It is found in bile and large intestine.
Taurine has multiple functions in the body including
conjugation of bile acids, antioxidant role,
osmoregulation, membrane stability and calcium
signaling.
It is important for the development of cardiovascular
system, development and function of skeletal system,
eyes and central nervous system.
Some reports suggest it can be used as treatment for
cirrhosis and essential hypertension in experimental
animals.
26
27. Keeping the Correct Structure of Proteins
Cysteine residues in polypeptide chains form
disulfide bridges to make active proteins, e.g.
insulin and immunoglobulins.
27
28. METABOLISM OF SULFUR
The sulfur present in body may be either organic sulfur
as a component of proteins (sulfur-containing amino
acids) or as part of sulfatides and glycosaminoglycans
(GAG).
Inorganic sulfur is derived from the sulfur-containing
amino acids by trans-sulfuration or desulfuration
reactions.
The H2S derived from cysteine may be oxidized to
sulfites and thiosulfates and further oxidized to sulfate.
The excretory forms of sulfur in urine are:
a. Inorganic sulfates,
b. Organic or ethereal sulfates, and
c. Neutral sulfur.
28
29. Active sulfate or Phosphoadenosine phospho-5’-sulfate
(PAPS) is formed by the reaction between ATP and
SO4 and the sulfate is attached to the ribose-5’-
phosphate.
PAPS is used for various sulfuration reactions, e.g.
synthesis of sulfatides, glycosaminoglycans, etc.
29
30. CYSTINUR
IA
Cystinuria is one of the inborn errors of metabolism.
It is an autosomal recessive condition.
The disorder is attributed to the deficiency in transport of
amino acids
Signs and symptoms include:
i. Abnormal excretion of cystine and to a lesser extent
lysine, ornithine and arginine. Hence the condition is also
called Cystine-lysinuria.
ii. Crystalluria and calculi formation. In acidic pH, cystine
crystals are formed in urine.
30
31. iii. Obstructive uropathy, which may lead to renal
insufficiency.
iv. Treatment is to increase urinary volume by increasing
fluid intake. Solubility of cystine is increased by
alkalanization of urine by giving sodium bicarbonate.
31
32. Cyanide-Nitroprusside Test:
It is a screening test. Urine is made alkaline with
ammonium hydroxide
and sodium cyanide is added. Cystine, if present, is
reduced to cysteine.
Then add sodium nitroprusside to get a magenta-red
colored complex.
Specific aminoaciduria
may be confirmed by chromatography.
32
33. CYSTINOSIS
It is a familial disorder characterized by the
widespread deposition of cystine crystals in the
lysosomes.
Cystine accumulates in liver, spleen, bone marrow,
WBC, kidneys, cornea and lymph nodes.
There is an abnormality in transport of cystine which
is responsible for the accumulation.
It is an autosomal recessive condition.
Microscopy of blood shows cystine crystals in WBCs.
Treatment policies are to give adequate fluid so as to
increase urine output, alkalinization of urine by
sodium bicarbonate, as well as administration of D-
penicillamine.
33
34. HOMOCYSTINURIAS
First described in 1962, these are the latest in the
series of inborn errors of metabolism.
All of them are autosomal recessive conditions with
Incidence of 1 in 200,000 births.
Normal homocysteine level in blood is 5–15
micromol/L.
In diseases, it may be increased to 50 to 100 times.
Moderate increase is seen in aged persons, vitamin
B12 or B6 deficiency, tobacco smokers, alcoholics and
in hypothyroidism..
In plasma, homocysteine (with -SH group) and
homocysteine (disulfide, -S-S- group) exist. Both of
them are absent in normal urine; but if present, it will
be the homocysteine (disulfide) form.
34
35. If homocysteine level in blood is increased, there is
increased risk for coronary artery diseases.
Other important diseases associated with
hyperhomocysteinemia are neurological disorders
(stroke), pre-eclampsia of pregnancy, chronic
pancreatitis, etc.
35Enzyme deficiency in homocystinurias (pyridoxal phosphate co enzyme)
Characterized by:
a. high urinary levels of
Hcy,
b. high plasma levels of
Hcy and methionine
and
c. low plasma levels of
cysteine
36. CYSTATHIONINE BETA SYNTHASE
DEFICIENCY
1. It causes elevated plasma levels of methionine
and homocysteine. There is increased excretion of
methionine and homocystine in urine. Plasma
cysteine is markedly reduced.
2. General symptoms are mental retardation and
Charley Chaplin gait. Skeletal deformities are
also seen.
3. In eyes, ectopia lentis (subluxation of lens),
myopia and glaucoma may be observed.
36
37. 4. Homocysteine causes activation of Hageman’s factor.
This may lead to increased platelet adhesiveness and
life-threatening intravascular thrombosis.
5. Cyanide-nitroprusside test will be positive in urine.
Urinary excretion of homocystine is more than 300
mg/24 h.
6. Plasma homocysteine and methionine levels are
increased.
7. Treatment is a diet low in methionine and rich in
cysteine. Sometimes the affinity of apo-enzyme to the
co-enzyme is reduced. In such cases, pyridoxal
phosphate, the co-enzyme given in large quantities
(500 mg) will correct the defect.
37
38. COBALAMIN DEFICIENCY
The enzyme, N5-methyl-THFA-homocysteine-
methyl-transferase is dependent on vitamin B12.
Therefore, vitamin B12 deficiency may produce
alteration in methionine metabolism.
Blood contains increased level of homocysteine, but
methionine level is low. Urine contains
homocysteine.
38
39. DEFICIENT N5, N10-
METHYLENE THFA
REDUCTASE
This enzyme catalyzes the reaction N5, N10-methylene-
THFA to N5-methyl-THFA
Deficiency of this enzyme leads to reduced methionine
synthesis with consequent increase in homocystine level
in urine.
Behavioral changes and vascular abnormalities may be
observed.
Folate supplementation is beneficial. MTHFR gene
polymorphism (MTHFR C677T) is seen in
hyperhomocysteinemia.
39
40. CYSTATHIONINURIA
It is due to cystathionase deficiency.
It is an autosomal recessive condition.
Mental retardation, anemia, thrombocytopenia, and
endocrinopathies accompany this condition.
Less severe forms may be seen in conditions interfering
with homocysteine remethylation, in B12 deficiency
and in impaired folate metabolism.
Acquired Cystathioninuria may be due to pyridoxine
deficiency.
It may also be seen in liver diseases and after
thyroxine administration.
Diagnosis rests on cyanide-nitroprusside test
(negative) and detection of cystathionine in urine.
Large quantities of pyridoxine (200–400 mg) may be
beneficial.
40
41. ACQUIRED
HYPERHOMOCYSTEINEMIAS
a. Nutritional deficiency of vitamins, such as
cobalamin, folic acid and pyridoxine.
b. Metabolic: Chronic renal diseases,
hypothyroidism.
c. Drug induced: Folate antagonists, vitamin B12
antagonists; pyridoxine antagonists; estrogen
antagonists, nitric oxide antagonists.
41
42. An increase of 5 micromol/L of homocysteine in serum
elevates the risk of coronary artery disease by as
much as cholesterol increase of 20 mg/dL.
Homocysteine interacts with lysyl residues of collagen
interfering with collagen cross linking.
Homocysteine interacts with lysyl aldehyde groups on
collagen and bind to fibrillin producing endothelial
dysfunction.
Many patients with homocysteinemia also have
Marfanoid features since the protein fibrillin is
defective.
It forms homocysteine thiolactone, a highly reactive
free radical which thiolates LDL particles.
42
43. These particles tend to aggregate, are endocytosed
by macrophages and increase the tendency for
atherogenesis.
Providing adequate quantity of pyridoxine, vitamin
B12 and folic acid will keep homocysteine in blood
at normal levels.
Maternal hyperhomocysteinemia is known to
increase the chances of neural tube defects in fetus.
So, high doses of folic acid are advised in pregnancy.
43
44. SUMMARY
A summary of methionine metabolism is shown with
the roles played by vitamins. 44