Xanthinuria
Xanthinuria, also known as xanthine oxidase deficiency, is a rare genetic disorder causing the accumulation of xanthine. It is caused by a deficiency of the enzyme xanthine oxidase.
Orotic aciduria
Orotic aciduria is a disease caused by an enzyme deficiency resulting in a decreased ability to synthesize pyrimidines. It is the only known enzyme deficiency of the de novo pyrimidine synthesis pathway.
Gout
Gout is caused by a condition known as hyperuricemia, where there is too much uric acid in the body.
Homocystinuria is a disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites (homocystine, homocysteine-cysteine complex, and others) in blood and urine. Normally, these metabolites are not found in appreciable quantities in blood or urine.
Amino acid metabolism disorders are hereditary metabolic disorders. Hereditary disorders occur when parents pass the defective genes that cause these disorders on to their children. Amino acids are the building blocks of proteins and have many functions in the body. Hereditary disorders of amino acid processing (metabolism) can result from defects either in the breakdown of amino acids or in the body’s ability to get amino acids into cells.
Homocystinuria is a disorder of methionine metabolism, leading to an abnormal accumulation of homocysteine and its metabolites (homocystine, homocysteine-cysteine complex, and others) in blood and urine. Normally, these metabolites are not found in appreciable quantities in blood or urine.
Amino acid metabolism disorders are hereditary metabolic disorders. Hereditary disorders occur when parents pass the defective genes that cause these disorders on to their children. Amino acids are the building blocks of proteins and have many functions in the body. Hereditary disorders of amino acid processing (metabolism) can result from defects either in the breakdown of amino acids or in the body’s ability to get amino acids into cells.
Protein which are major component of our diet have amino acid as their precursor and also act as important energy source. Any imbalance in the metabolism of these amino acid cause disorders
MSUD is metabolic genetic error . It happens due to lack of an enzyem that degrades specific amino acids
Homocystinuria is also a metbolic genetic error due to an enzyme defficiency it leads to an accumulation of homocystein and related chemical in the blood
inborn errors of metabolism. Inborn errors of metabolism are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food
Inborn errors of metabolism
Definition:- Inborn errors of metabolism occur from a group of rare genetic disorders in which the body cannot metabolize food components normally.
These disorders are usually caused by defects in the enzymes involved in the biochemical pathways that break down food components.
Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine.
Inborn errors of amino acid metabolismRamesh Gupta
Inherited disorders of amino acid metabolism e.g. phenylketonuria, maple syrup urine disease, alkaptonuria, homocystinuria, Hartnup disease etc for medical, biochemistry and biology undergraduates
DISORDER OF URIC METABOLISM -GOUT-INVESTIGATIONS AND DIAGNOSIS.pdfMoses Dumbuya
Basic Chemical pathology review
Gouty arthritis and other uric acid metabolic disorders, gout , hyperuricemia,hypouricemia , Xanthinuria and lesch- Nyhan syndrome
Uric acid metabolism for medical students
Protein which are major component of our diet have amino acid as their precursor and also act as important energy source. Any imbalance in the metabolism of these amino acid cause disorders
MSUD is metabolic genetic error . It happens due to lack of an enzyem that degrades specific amino acids
Homocystinuria is also a metbolic genetic error due to an enzyme defficiency it leads to an accumulation of homocystein and related chemical in the blood
inborn errors of metabolism. Inborn errors of metabolism are rare genetic (inherited) disorders in which the body cannot properly turn food into energy. The disorders are usually caused by defects in specific proteins (enzymes) that help break down (metabolize) parts of food
Inborn errors of metabolism
Definition:- Inborn errors of metabolism occur from a group of rare genetic disorders in which the body cannot metabolize food components normally.
These disorders are usually caused by defects in the enzymes involved in the biochemical pathways that break down food components.
Maple syrup urine disease is an inherited disorder in which the body is unable to process certain protein building blocks (amino acids) properly. The condition gets its name from the distinctive sweet odor of affected infants' urine.
Inborn errors of amino acid metabolismRamesh Gupta
Inherited disorders of amino acid metabolism e.g. phenylketonuria, maple syrup urine disease, alkaptonuria, homocystinuria, Hartnup disease etc for medical, biochemistry and biology undergraduates
DISORDER OF URIC METABOLISM -GOUT-INVESTIGATIONS AND DIAGNOSIS.pdfMoses Dumbuya
Basic Chemical pathology review
Gouty arthritis and other uric acid metabolic disorders, gout , hyperuricemia,hypouricemia , Xanthinuria and lesch- Nyhan syndrome
Uric acid metabolism for medical students
It gives basic things regarding urinalysis and will be very useful for medical students, house surgeons, laboratory technicians and postgraduates in medicine.
explains the breakdown of purine. source and excretion of purine is explained. hyperuricemia and hypouricemia is discussed. types of Gout, clinical features and treatment is included.
INTRODUCTION
Cancer is a general term used to refer to a condition where the body’s cells begin to grow and reproduce in an uncontrollable way. Lung cancers are the fourth most common cancer reported in the Indian males.
DEFINITION
Lung carcinoma is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung by the process of metastasis into nearby tissue or other parts of the body.
CAUSES
The most common causes of fracture include,
I. Tobacco smoke
Tobacco use is responsible for more than one of every six deaths. The younger a person is when he or she starts smoking, the greater the risk of developing lung cancer.
II. Secondhand smoke
Passive smoking has been identified as a possible cause of lung cancer in nonsmokers. People who are involuntarily exposed to tobacco smoke in a closed environment (house, automobile, and building) have an increased risk of lung cancer when compared with unexposed nonsmokers.
III. Environmental and occupational exposure
Various carcinogens have been identified in the atmosphere, including motor vehicle emissions and pollutants fromrefineries and manufacturing plants. High levels of radon have been associated with the development of lung cancer, especially when combined with cigarette smoking. Chronic exposure to industrial carcinogens, such as arsenic, asbestos, mustard gas, chromates, coke oven fumes, nickel, oil, and radiation has been associated with the development of lung cancer.
IV. Genetics
Some familial predisposition to lung cancer seems apparent, because the incidence of lung cancer in close relatives of patients with lung cancer appears to be two to three times that in the general population regardless of smoking status.
TYPES OF LUNG CANCER:
1. Small cell lung carcinoma
• Accounts for 15%-25% of lung cancers
• It is most malignant form
• Tends to spread early via lymphatic and bloodstream
• Is frequently associated with endocrine disturbances
• Predominantly central and can cause bronchial obstruction and pneumonia.
2. Non-small cell lung carcinoma
Is further classified by cell type,
Adenocarcinoma
• Most common type
• Accounts for approximately 30%-40% of lung cancers
• More common in women
• Often gas no clinical manifestations until widespread metastasis is present
• Usually begins in mucous glandular tissue, is most commonly located in peripheral portions of lungs.
Squamous cell carcinoma
• Second most common type of lung cancer
• Accounts for 30%-35% of lung cancers
• Is more common in men
• Arises from the bronchial epithelium of the lungs or bronchus, slow-growing cancer that usually begins in the bronchial tubes.
Large cell carcinoma
• The least common form
• Accounts for 5%-15% of lung cancers
• Composed of large sized cells that are anaplastic and often arise in the bronchi, commonly causes cavitation
• Is highly metastatic via lymphatic and blood.
STAGING OF NON-SMALL CELL LUNG C
nausea and vomiting in pregnancy is very common. it may be a manifestation of some medical - surgical - gynecological complications. hyperemesis gravidarum is a severe type of vomiting in pregnancy which has got deleterious effects on the health of the mother. it is a very important topic and it is also a topic in obstetrics. we should encourage and help young mothers to identify the symptoms. please read it and get knowledge about nausea and vomiting in pregnancy. stay tuned.
Albinism is a genetic condition where people are born without the usual pigment (color) in their bodies. Their bodies aren't able to make a normal amount of melanin, the chemical that is responsible for eye, skin, and hair color. So most people with albinism have very pale skin, hair, and eyes.
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Alkaptonuria is a rare genetic metabolic disorder characterized by the accumulation of homogentisic acid in the body. Affected individuals lack enough functional levels of an enzyme required to breakdown homogentisic acid. Affected individuals may have dark urine or urine that turns black when exposed to air.
Tumor markers are substances, such as proteins, biochemicals, hormones or enzymes, produced by tumor cells or by the body in response to tumor cells. As tumor cells multiply, cancer spreads, and tissue is damaged, these substances increase and leak into the bloodstream. Tumor marker levels in blood help physicians evaluate people for certain types of cancer
Free radicals damage contributes to the etiology of many chronic health problems such as cardiovascular and inflammatory disease, cataract, and cancer. Antioxidants prevent free radical induced tissue damage by preventing the formation of radicals, scavenging them, or by promoting their decomposition.
A carcinogenic agents or carcinogen is any substances, chemicals, medical or environmental radiation, some viruses, lifestyle factors, and even some medications that promotes carcinogenesis, the formation of cancer. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes
Cancer is the uncontrolled growth of abnormal cells anywhere in a body
Causative agents – chemical, toxic compound exposures, ionizing radiation, some pathogens
Most cancer form tumors, but not all tumors are cancerous.
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11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
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As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
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This presentation explores a brief idea about the structural and functional attributes of nucleotides, the structure and function of genetic materials along with the impact of UV rays and pH upon them.
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Immuno deficiency disorder Associated with purine metabolism
1. Confidential Customized for Lorem Ipsum LLC Version 1.0
IMMUNODEFICIENCY DISEASES
ASSOCIATED WITH DEFECTS IN
PURINE NUCLEOTIDE
METABOLISM
Dr. V. MAGENDIRA MANI
Assistant Professor of Biochemistry
Islamiah College (Autonomous),
Vaniyambadi
magivbio@gmail.com
2. 0
1
Xanthinuria, also known as
xanthine oxidase deficiency, is
a rare genetic disorder
causing the accumulation of
xanthine. It is caused by a
deficiency of the enzyme
xanthine oxidase.
0
2
Orotic aciduria is a disease
caused by an enzyme
deficiency resulting in a
decreased ability to
synthesize pyrimidines. It is
the only known enzyme
deficiency of the de novo
pyrimidine synthesis pathway.
0
3
Gout is caused by a condition
known as hyperuricemia,
where there is too much uric
acid in the body.
Xanthinuria Orotic aciduria Gout
3.
4. Confidential Customized for Lorem Ipsum LLC Version 1.0
Xanthinuria
Xanthinuria, is a rare genetic disorder causing the
accumulation of xanthine.
It is caused by a deficiency of the enzyme xanthine
oxidase.
It was first formally characterized in 1954.
5. Overview
Hereditary xanthinuria is a purine metabolic disorder due to
inherited deficiency of the xanthine dehydrogenase/oxidase
enzyme and is characterized by very low (or undetectable)
concentrations of uric acid in blood and urine and very high
concentration of xanthine in urine, leading to urolithiasis.
Urolithiasis - A small, hard deposit (stones) that forms in the kidneys and
is often painful when passed
6.
7. Causes
1 Type I xanthinuria can be caused by
a deficiency of xanthine
dehydrogenase, which is an
enzyme necessary for converting
xanthine to uric acid
2 Type II xanthinuria caused by
molybdenum cofactor deficiency
lack one or two other enzyme
activities in addition to xanthine
3 Xanthinuria can be caused by
mutations in the xanthine
dehydrogenase gene,
aldehyde oxidase gene, or
the molybdenum cofactor
gene.
4
Xanthinuria may also
be caused by
treatment of uric acid
excretion with
allopurinol therapy.
8. Symptoms
➔ Haematuria,
➔ Nausea,
➔ Vomiting,
➔ Abdominal pain,
➔ Joint pain,
➔ Failure to thrive,
➔ Fever,
➔ Flank pain,
➔ Dysuria,
➔ Urinary tract infection,
➔ Renal colic,
➔ Acute renal failure,
➔ Crystalluria / urolithiasis.
➔ Kidney stones
In some rare patients, renal disease may evolve to renal failure, or may
even induce arthropathy, myopathy or duodenal ulcer
Flank pain - upper abdominal pain, Dysuria - painful or difficult urination. Renal colic - pain you
get when urinary stones block part of your urinary tract. Haematuria - blood in urine
9. Diagnosis
➔ Diagnosis is based on estimation of uric acid in blood and urine
If hypouricemia is confirmed, detailed purine metabolic
investigation follows, and includes measurement of xanthine
and hypoxanthine in urine and plasma.
➔ Ultrasonography - reveals the presence of xanthine
urolithiasis
➔ Allopurinol loading test, xanthine oxidase assay and molecular
analysis.
10. Treatment
There is no specific treatment beyond maintaining a high fluid
intake and avoiding foods that are high in purine, avoiding foods
and drinks that contain xanthine derivatives, such as coffee, tea,
and cola
12. Orotic aciduria
Orotic aciduria refers to an excessive excretion of orotic acid in urine.
Orotic acid is an intermediate product in pyrimidine synthesis pathway, a
subsequent product of which plays a role in conversion between dihydrofolate
and tetrahydrofolate.
Orotic aciduria is associated with megaloblastic anemia due to decreased
pyrimidine synthesis, which leads to decreased nucleotide-lipid cofactors
needed for erythrocyte membrane synthesis in the bone marrow.
13. Signs and symptoms
➔ It causes a characteristic form of anemia and may be associated with
mental and physical retardation.
➔ In addition to the characteristic excessive orotic acid in the urine, patients
typically have megaloblastic anemia which cannot be cured by
administration of vitamin B12 or folic acid
➔ It also can cause inhibition of RNA and DNA synthesis and failure to thrive.
This can lead to mental and physical retardation
14. Genetics
Orotic aciduria has an autosomal recessive of
inheritance.
Its can be caused by a deficiency in the enzyme
Uridine Monophosphate Synthetase, a
bifunctional protein that includes the enzyme
activities of orotate phosphoribosyltransferase and
orotidine 5'-phosphate decarboxylase.
It can also arise secondary to blockage of the urea
cycle, particularly in ornithine transcarbamylase
deficiency (or OTC deficiency).
15. Diagnosis
➔ A diagnosis of hereditary orotic aciduria is based upon identification
of characteristic symptoms, a detailed patient and family history, a
thorough clinical evaluation and examination of the urine.
➔ Examination of the urine (urinalysis) can reveal elevated levels of
orotic acid.
➔ Orotic aciduria can be diagnosed through genetic sequencing of the
UMPS gene.
➔ Hereditary orotic aciduria by assessing blood ammonia levels and
blood urea nitrogen (BUN).
16. ➔ Treat with feeding diet rich in Uridine /Cytidine
➔ This provide Pyrimidine nucleotides through Salvage Pathway.
➔ Promotes DNA and RNA synthesis.
➔ Also the introduced Pyrimidine bases inhibits CPS II enzyme by
feed back mechanism and block synthesis of Oroticaciduria.
Treatment
19. Gout is a common metabolic disorder of Purine
metabolism characterized by :
● Persistent Hyperuricemia
● Hyperuricaciduria and
● Joint pain
20. ➔ Gout, is a disease of the joints, usually in males, caused by an
elevated concentration of uric acid in the blood and tissues.
➔ The joints become inflamed, painful, and arthritic, owing to
the abnormal deposition of crystals of sodium urate.
➔ The kidneys are also affected, because excess uric acid is
deposited in the kidney tubules.
● Primary Gout (Genetic Cause)
● Secondary Gout
Types of Gout
21.
22. Basic cause of primary Gout is genetic
cause.
It has Enzyme defects concerned with:
➔ Over Production Of Purine
Nucleotides
➔ Over catabolism of Purine
Nucleotides
➔ Results in Hyperuricemia
1. Ribose-phosphate diphosphokinase
(Increased Activity))
2. PRPP Glutamyl Amido Transferase
(Increased Activity)
3. Hypoxanthine-guanine
phosphoribosyltransferase
(Decreased Activity)
4. Glucose 6 Phosphatase
(Decreased Activity)
5. Glutathione Reductase
(Decreased Activity)’
5 Enzyme Defects
Causing Primary Gout
23. ● The defect of above 5 Enzymes in primary Gout
● Directly or indirectly increases the Denovo Biosynthesis of Purine
nucleotides.
● There is overproduction of Purine Nucleotides more than their
functional use
● Which further catabolizes them to produce increased Uric acid
levels (Hyperuricemia)
24. ● It is an acquired cause:
● In some pathological states where there is abnormal and excessive
breakdown of cells releases Nucleic acids and Nucleotides.
● Whose catabolism produces increased Uric acid levels
(Hyperuricemia)
Conditions Of Secondary Gout
25. Renal Gout
➔ Type of Gout caused due to insufficiency of Renal System.
➔ Where there is reduced excretion of Uric acid through Urine.
➔ Retention of the Uric acid in blood leading to Hyperuricemia.
➔ Renal Failure
➔ Use of Thiazide diuretics (Drug increase urine flow)
➔ Metabolic Acidosis
➔ Ketoacidosis and Lacticacidosis affects the excretion of Uric
acid through Urine.
Conditions Of Renal Gout
26. ➔ The increased Uric acid levels
➔ Decreases the solubility of Uric acid
and
➔ Get crystallized to form Mono Sodium
Urate Crystals.
➔ The Mono Sodium Urate Crystals get
deposited in the synovial spaces of
joints form Tophi (Hard Mass/
Swelling)
27. —Deposition of Urate crystals in synovial
spaces affects the movements of joints.
—Leads to pain , inflammation, stiffness and
redness of joints known as Gouty Arthritis.
29. ● Obesity (High BMI)
● Hypertension (HTN )
● Use of Thiazide diuretics
● Diet high in meat &
seafood
● Excess Alcohol use
Highest with Beer
● Male Gender
● Postmenopausal female
● Older Persons
● Pharmaceuticals:
Cyclosporine
30. The normal serum Uric acid level in adults is 2-7 mg%
—0.5-1 g of uric acid is formed daily in the organism.
—In Gout the serum Uric acid levels rises above 8 mg%.
● History taking & physical examination
● Family history of Gout
● Clinical symptoms alone are sufficient to make accurate diagnosis
in most cases
● Performing Diagnostic studies may help in knowing the stage and
progression of Gout.
Diagnosis
31. ➔ Examination of joint fluid (Arthrocentesis extraction of joint fluid).
➔ X-rays of joint
➔ Blood Examination
➔ Serum Uric acid levels usually elevated.
➔ 24 hour urine Uric acid levels increased.
➔ WBC Count elevated during acute attacks.
➔ ESR (elevated)
32. Treatment
➔ Bed rest : No much movements of joints.
➔ Bed rest : With a position for comfort
➔ Local application of heat or cold around the joint area.
➔ Restrict intake of diet rich in Purine content.
➔ Restrict Alcohol consumption
➔ Avoid dehydration
➔ Drink lots of Water
➔ Allopurinol (Zyloprim) is a drug of choice for Treatment of Gouty
arthritis.
➔ Allopurinol is a structural analog of Hypoxanthine.
33.
34. Thank you...
Dr. V. MAGENDIRA MANI
Assistant Professor of Biochemistry
Islamiah College (Autonomous),
Vaniyambadi
magivbio@gmail.com