The document summarizes the pentose phosphate pathway and uronic acid pathway. The pentose phosphate pathway generates NADPH and ribose-5-phosphate. It occurs in the cytosol of liver, adipose tissue and erythrocytes. A defect in glucose-6-phosphate dehydrogenase, which catalyzes the first step of the pathway, can cause hemolytic anemia. The uronic acid pathway converts glucose to glucuronic acid and is important for conjugating substances like bilirubin for excretion. Disruptions can cause essential pentosuria or oxalosis.
This PPT contains HMP Shunt, Reactions of the pathway i.e. Oxidative & Non-oxidative. Glucose-6-Phosphate dehydrogenase (G6PD) deficiency, Regulation of Pathway, Significance of HMP shunt
This PPT contains HMP Shunt, Reactions of the pathway i.e. Oxidative & Non-oxidative. Glucose-6-Phosphate dehydrogenase (G6PD) deficiency, Regulation of Pathway, Significance of HMP shunt
HMP shunt pathway is a shunt pathway from glycolytic pathway. starting form glucose 6 pasphat by the action of an enzymes known as g6pd. by this pathway an important reducing substance named NADPH2 is produce which result in reducing other substances for its synthesis.
Pentose phosphate pathway is also called Hexose monophosphate pathway/ HMP shunt/ Phosphogluconate pathway.
It is an alternative route for the metabolism of glucose.
It is more complex pathway than glycolysis.
It is more anabolic in nature.
It takesplace in cytosol.
The tissues such as liver, adipose tissue, adrenal gland, erythrocytes,testes and lactating mammary gland are highly active in HMP shunt.
It concern with the biosynthesis of NADPH and pentoses.
Pentose phosphate pathway is an alternative pathway to glycolysis and TCA cycle for oxidation of glucose. It is a shunt of glycolysis. It is also known as hexose monophosphate (HMP) shunt or phosphogluconate pathway. It occurs in cytoplasm of both prokaryotes and eukaryotes. While it involves oxidation of glucose, its primary role is anabolic rather than catabolic. It is an important pathway that generates precursors for nucleotide synthesis and is especially important in red blood cells (erythrocytes).
HMP shunt pathway is a shunt pathway from glycolytic pathway. starting form glucose 6 pasphat by the action of an enzymes known as g6pd. by this pathway an important reducing substance named NADPH2 is produce which result in reducing other substances for its synthesis.
Pentose phosphate pathway is also called Hexose monophosphate pathway/ HMP shunt/ Phosphogluconate pathway.
It is an alternative route for the metabolism of glucose.
It is more complex pathway than glycolysis.
It is more anabolic in nature.
It takesplace in cytosol.
The tissues such as liver, adipose tissue, adrenal gland, erythrocytes,testes and lactating mammary gland are highly active in HMP shunt.
It concern with the biosynthesis of NADPH and pentoses.
Pentose phosphate pathway is an alternative pathway to glycolysis and TCA cycle for oxidation of glucose. It is a shunt of glycolysis. It is also known as hexose monophosphate (HMP) shunt or phosphogluconate pathway. It occurs in cytoplasm of both prokaryotes and eukaryotes. While it involves oxidation of glucose, its primary role is anabolic rather than catabolic. It is an important pathway that generates precursors for nucleotide synthesis and is especially important in red blood cells (erythrocytes).
Reference Harper Illustrated book of Biochemistry
Applying laws of Thermodynamics to Biochemistry.
Diferent types of Reactions, exergonic and edergonic,
Illustrated explain of Role of ATP in our body,
Brief concept on ATP production and high energy phosphate,
ATP/ADP cycle and about Creatine Kinase
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
- 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
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Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
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
4. Historical aspect
• 1930: first existence of pentose
phosphate pathway was
obtained by Otto Warburg. He
discovered NADP+ through his
studies on the oxidation of
glucose 6-phosphate to 6-
phosphogluconate
• 1950: PPP was elucidated by
Frank Dickens, Bernard
Horecker, Fritz Lipmann and
Efraim Racker
Bernard Leonard Horecker began his training
in enzymology in 1936 as a graduate student
at University of Chicago in laboratory of T. R.
Hogness. His initial project involved studying
succinic dehydrogenase from beef heart using
the Warburg manometric apparatus. However,
when Erwin Hass arrived from Otto Warburg's
laboratory he asked Horecker to join him in
search for an enzyme that would catalyze
reduction of cytochrome c by reduced NADP.
This was the beginning of Horecker's lifelong
involvement with pentose phosphate
pathway.
5. Introduction
• Occurs in cytosol. The tissues such
as liver, adipose tissue, adrenal
gland, erythrocytes, testes and
lactating mammary gland are
highly active in HMP shunt.
• Of particular importance in these
tissues is the oxidation of glucose
6-phosphate to pentose
phosphates by pentose phosphate
pathway so, also called as
phosphogluconate pathway or the
hexose monophosphate pathway.
• Unique multifunctional
pathway where there are
several interconvertible
substances produced
which may proceed in
different directions in the
metabolic reactions.
• an alternative pathway to
glycolysis and is used to
produce ribose-5-
phosphate and nicotinamide
adenine dinucleotide
phosphate (NADPH)
7. • Begins with the glycolytic
intermediate: Glucose 6-P.
• Two phases
1) Oxidative phase
2) Non oxidative phase
• Ribose 5 phosphate acts as a
precursor in synthesis of
nucleotides, coenzymes, DNA and
RNA
• Demand in actively dividing cells.
• NADPH is used in reductive
biosynthesis
• NADPH maintains reducing
environment on cells.
8. Need/Importance of HMP pathway
1. Ribose-5-phosphate required for the
biosynthesis of DNA and RNA are
provided by this pathway
2. It provides the route for the
interconversion of pentoses to hexoses.
3. It generates NADPH which is required
for the biosynthesis of fatty acids,
cholesterol, steroid hormones and
neurotransmitters.
4. NADPH also keeps the iron of
hemoglobin in ferrous state and prevents
the formation of methemoglobin.
5. NADPH is important for phagocytosis
carried out by WBCs
13. Wernicke-Korsakoff Syndrome Is Exacerbated by a Defect in
Transketolase
• Wernicke-Korsakoff syndrome, a mutation in
gene for transketolase results in an enzyme
having an affinity for its coenzyme TPP that is
one-tenth that of normal enzyme.
• Although moderate deficiencies in the vitamin
thiamine have little effect on individuals with
an unmutated transketolase gene, in those
with altered gene, thiamine deficiency drops
level of TPP below that needed to saturate
enzyme.
• Lowering of transketolase activity slows
pentose phosphate pathway, and results WKS.
• More common among alcoholics; chronic
alcohol consumption interferes with
intestinal absorption of some vitamins,
including thiamine
15. The metabolism of glucose 6-phosphate by the
pentose phosphate pathway is coordinated with
glycolysis
• G6PD enzyme is allosterically
stimulated by NADP+ and
strongly inhibited by NADPH.
The ratio of NADPH:NADP+ is
the primary mode of
regulation for the enzyme and
is normally about 100:1 in liver
cytosol.
• Glucose 6 phosphate is
metabolized by both glycolytic
and pentose phosphate
pathway
• The cytoplasmic concentration
of NADP+ plays a key role in
determining the fate of glucose
6- phosphate
The rate of PPP is controlled by
level of NADP+
The flow of glucose 6 phosphate
depends upon the need for
NADPH, ribose 5 phosphate and
ATP
16. 1) Much more ribose 5-
phosphate than NADPH
is required
2) The needs for NADPH
and for ribose 5-phosphate
are balanced
17. 3) Much more NADPH than
ribose 5-phosphate is
required
4) Both NADPH and ATP are
required
18. Glucose-6-Phosphate Dehydrogenase
• G-6-PD is an oxidoreductase
that catalyzes the oxidation of
glucose-6- phosphate to 6-
phosphogluconate or the
corresponding lactone.
• Reaction is important as first
step in pentose-phosphate
shunt of glucose metabolism
with ultimate production of
NADPH
Tissue Source
adrenal cortex, spleen, thymus,
lymph nodes, lactating
mammary gland, and
erythrocytes.
Little activity is found in normal
serum.
“Most of the interest of G-6-PD focuses
on its role in the erythrocyte.”
19. • The enzyme is active as a
tetramer or dimer
• The monomer of G6PD
consists of 515
aminoacids and
molecular weight of 59
kDa.
• The G6PD gene is located
at the telomeric region
of long arm of X
chromosome
• Maintain NADPH in reduced form.
• Adequate concentration of NADPH is required to regenerate sulfhydryl-
containing proteins, such as glutathione, from oxidized to reduced state.
• Glutathione in the reduced form, in turn, protects hemoglobin from
oxidation by agents that may be present in the cell
doi:10.1016/S0140-6736(08)60073-2
20. Glucose 6-phosphate dehydrogenase deficiency
• NADPH enables cells to counterbalance oxidative stress
• Pentose phosphate shunt provides the reducing power of red cell in
the form of NADPH , maintaining glutathione in reduced form (GSH)
via closely linked glutathione pathway.
• GSH protects the red cells from oxidative damage;
inadequate supplies result in peroxidation of red cell membrane,
denaturation of haemoglobin and its precipitation as Heinz bodies,
resulting in reduced cell deformability and intravascular haemolysis
• G6PD deficiency is an X-linked, hereditary genetic defect caused by
mutations in the G6PD gene
• Most common clinical manifestation: neonatal jaundice and acute
hemolytic anemia
• Present in more than 400 million people worldwide
21. Epidemiology of G6PD deficiency
Luzzatto L, Ally M, Notaro R. Glucose-6-phosphate dehydrogenase deficiency. Blood. 2020
Sep 10;136(11):1225-1240.
22. The disorder can result in several
different clinical manifestations, one
of which is drug-induced hemolytic
anemia.
When exposed to an oxidant drug
such as primaquine, an antimalarial
drug, affected individuals experience
a hemolytic episode.
The severity of the hemolysis is
related to the drug concentration.
C15H21N3O
https://pubchem.ncbi.nlm.nih.gov/compound/
Primaquine
23. NADPH enables cells to counterbalance
oxidative stress.
Heinz body supravital
staining
Patient presented with severe NNJ requiring exchange
blood transfusion; he then had severe anemia requiring
frequent blood tranfusions. At age of 9 he was
splenectomized, whereupon he became transfusion-
independent. Note the persistent reticulocytosis,
remitted after splenectomy. The underlying unique
variant was G6PD Harilaou (class I: F216L) Luzzatto L, Ally M, Notaro R. Glucose-6-
phosphate dehydrogenase deficiency. Blood.
2020 Sep 10;136(11):1225-1240.
24. G6PD and Malaria
• In vitro studies show that growth of one malaria parasite,
Plasmodium falciparum, is inhibited in G6PD- deficient
erythrocytes.
• The parasite is very sensitive to oxidative damage and is killed by
a level of oxidative stress that is tolerable to a G6PD- deficient
human host.
• When G6PD deficient red cells are infected by P falciparum they
are sensed by macrophages as abnormal at an early stage, and
therefore they are removed: this seems a highly plausible
protective mechanism
Luzzatto L, Ally M, Notaro R. Glucose-6-phosphate dehydrogenase deficiency. Blood.
2020 Sep 10;136(11):1225-1240.
26. • Another alternative glucose oxidation pathway, does not lead to
the formation of ATP.
• In liver, it catalyzes the conversion of glucose to glucuronic acid,
ascorbic acid (except in human beings and other species) and
pentose.
• Source of glucuronic acid for conjugation of several endogenous
and exogenous substances like bilirubin, steroids, drugs before
excretion as glucuronides in urine and bile.
• GAG synthesis- Heparin, Hyaluronic acid, Dermatan sulfate.
27.
28. Uronic acid pathway: Significance
UDP Glucose UDP Glucoronic acid
• Synthesis of Glycogen
• Metabolism of Galactose
• Lactose synthesis
• Formation of UDP-
Glucoronic acid
• Biosynthesis of ascorbic
acid in lower animals
• Detoxification reactions
(bilirubin and steroid hormone)
• Biosynthesis of GAG
(hyaluronic acid and heparin)
• Biosythesis of L- iduronic acid
- An epimer of Glucoronic acid
- (heparin sulphate and
dermatan sulphate)
29. Clinical importance of Uronic acid pathway
Disruption of uronic acid pathways can be caused by
enzyme defect and administration of certain drugs.
1. Essential pentosuria :
• An inherited disorder.
• Due to deficiency of enzyme L- Xylitol
dehydrogenase or Xylulose kinase.
• Appearance of xylulose and excretion in urine
.
2. Oxalosis:
• Parenteral administration of xylitol may lead
to oxalosis, calcium oxalate deposition in
brain and kidney.
30. References
• Wilson J.L Biochemistry Lubert Stryer
• Lehninger Principles of Biochemistry
• Harper's Illustrated Biochemistry
• Fundamentals of Biochemistry Donald Voet, Judith G. Voet & Charlotte
W. Prat
• Luzzatto L, Ally M, Notaro R. Glucose-6-phosphate dehydrogenase
deficiency. Blood. 2020 Sep 10;136(11):1225-1240.
• https://pubchem.ncbi.nlm.nih.gov/compound/Primaquine