Metabolic Disorders

CHEM 4203

Fall 2008

CPS I DeficiencyCPS I Deficiency

What is carbamoyl Phosphate What is carbamoyl Phosphate Synthetase I?Synthetase I?

Enzyme found in the mitochondrial matrix Enzyme found in the mitochondrial matrix of liver cells.of liver cells.

Catalyzes the formation of Carbamoyl Catalyzes the formation of Carbamoyl Phosphate from ammonia, Carbon Phosphate from ammonia, Carbon dioxide, and two molecules of ATP.dioxide, and two molecules of ATP.

Important nitrogen acquiring reaction.Important nitrogen acquiring reaction. Important point of regulation in the urea Important point of regulation in the urea

cycle.cycle.

Carbamoyl phosphate is combined with Ornithine to form Citrulline, the first step in the Urea cycle.

Nitrogen is ultimately removed from the body as Urea.

Effect of CPSI DeficiencyEffect of CPSI Deficiency

A deficiency of the CPS I enzyme leads to A deficiency of the CPS I enzyme leads to a build up of ammonia in the liver.a build up of ammonia in the liver.

A build up of ammonia in the body can A build up of ammonia in the body can have severe effects such as lethargy, have severe effects such as lethargy, convulsions, and early death.convulsions, and early death.

It is a relatively rare disorder but it is hard It is a relatively rare disorder but it is hard to know the exact number of cases.to know the exact number of cases.

TreatmentTreatment

The initial treatment to reducing the levels The initial treatment to reducing the levels ammonia is to reduce protein intake, and ammonia is to reduce protein intake, and also possible administration of glucose also possible administration of glucose and lipid injections.and lipid injections.

If ammonia levels are high dialysis may be If ammonia levels are high dialysis may be necessary to remove the excess.necessary to remove the excess.

TyrosinemiaTyrosinemia

A Genetic DisorderA Genetic Disorder

John Thompson

PathologyPathology

Unable to metabolize tyrosineUnable to metabolize tyrosine Results in abnormally high Results in abnormally high

levels of tyrosine levels of tyrosine (hypertyrosinemia)(hypertyrosinemia)

Three different enzymes can Three different enzymes can cause three different cause three different pathological statespathological states

Type 1 TyrosinemiaType 1 Tyrosinemia

Most severe caseMost severe case Shortage of enzyme fumaryloacetate Shortage of enzyme fumaryloacetate

hydrolasehydrolase SymptomsSymptoms

Failure to grow at normal rateFailure to grow at normal rate BleedingBleeding DiarrheaDiarrhea VomitingVomiting JaundiceJaundice

Can lead to liver and kidney failureCan lead to liver and kidney failure

Type 2 TyrosinemiaType 2 Tyrosinemia

Shortage of tyrosine Shortage of tyrosine aminotransferaseaminotransferase

SymptomsSymptoms TearingTearing PhotophobiaPhotophobia Skin lesionsSkin lesions

Type 3 TyrosinemiaType 3 Tyrosinemia

Most rare caseMost rare case Shortage of 4-Shortage of 4-

hydroxyphenylpyruvate hydroxyphenylpyruvate dioxygenasedioxygenase

SymptomsSymptoms Mild mental retardationMild mental retardation SeizuresSeizures AtaxiaAtaxia

TreatmentTreatment

Low protein dietLow protein diet Liver transplant (type 1)Liver transplant (type 1) Nitisinone (type 1)Nitisinone (type 1)

Tam TranCHEM 4203

November 11, 2008

A genetic disorder in which pigment melanin, which gives color to eyes, hair, and skin, is insufficiently produced or completely not produced.

Occurs in many types of animals. In humans, there is one albino in every

17,000 people. There are about 18,000 people affected

by Albinism in the United States.

Red eyes. Pale skin. White or pink hair.

(A) (B) (C)

Impaired vision due to insufficient amount of pigment.

Sensitive skin which is easily damaged by sun light. Cancer if not protected.

Minor difficulties in blood clotting and hearing sometimes.

Normal growth and development in humans.

Mutation of tyrosinase gene in melanocytes.

(D)

Mutation of tyrosinase gene in melanocytes.

(D)

No treatment for albinism.

Relieve symptoms caused by albinism.

+ UV sunglasses to protect eyes.+ Sunscreens and clothes to

prevent sunburn.+ Genetic counseling if albinism

existed in family history.

Pictures: (A) http://www.righthealth.com/Health/Human_Albino_Pictures/-od-images_5-s

(B) http://www.kellymilnerhalls.com/content/blogcategory/118/68/ (C) http://www.greenexpander.com/2007/12/04/animal-photo-set-5-albino-animals/ (D) http://albinism.med.umn.edu/factpath.gif

Sources:International Albinism Center at the University of Minnesota. Facts about Albinism. http://albinism.med.umn.edu/facts.htm. [accessed 2008 November 11]

Medical Center at University of Maryland. Albinism. 5 February 2008. http://www.umm.edu/ency/article/001479.htm. [accessed 2008 November 11]

Galactosemia

Tam Han

Galactose Metabolism Disorder

• Affects an individual’s ability to properly metabolize galactose.

• Defective in the conversion of galactose to glucose 1-phosphate.– Galactokinase– UDP-glucose 4-epimerase– Galactose 1-phosphate

uridylyltransferase• Metabolic processes

– Further metabolism of galactose

– Glycolysis

• Symptoms and effects– Galactose 1-phosphate

uridylyltransferase galactosemia (classic galactosemia)

– Galactokinase deficiency (galactosemia type 2 or GALK deficiency)

– Galactose epimerase deficiency

• Common?– Rare disorder– Relatively small gene pool

• Treatment– Strict removal of lactose and

galactose from diet

References

• Lehninger. Principles of Biochemistry, 4th edition. pp. 536-37.

• http://en.wikipedia.org/wiki/Galactosemia• http://en.wikipedia.org/wiki/Classic_galactosemia• http://en.wikipedia.org/wiki/

Galactokinase_deficiency• http://en.wikipedia.org/wiki/

Galactose_epimerase_deficiency

Maple Syrup Urine Disease

Jason O’Neal

Chem. 4203

Dr. Clower

What is it?What is it?

Genetic Disorder Autosomal recessive metabolic

disorder

What process is Disrupted?

What process is Disrupted?

The genetic defect causes a deficiency of branched-chain Alpha-keto acid dehydrogenase complex

Keeps branched chain amino acids from being broken down

So what’s the Problem?So what’s the Problem?

A build-up of these AA’s, leucine, isoleucine, and valine, and toxic by-products

Symptoms and Effects- Urine smells like maple syrup Vomiting, feeding difficulties, avoiding

food, coma, lethargy Infants may suffer from brain damage and

developmental problems If untreated die within first months of life

How common is it?How common is it?

It affects 1 out of 120,000 live births Treatment- Involves a protein-free diet, diet free of

branched chain amino acids. Must remain on this diet to avoid

neurological damage.

ReferencesReferences

http://www.savebabies.org/diseasedescriptions/msud.php

http://www.emedicine.com/PED/topic1368.htm emedicine

http://www.nlm.nih.gov/MEDLINEPLUS/ency/article/000373.htm

Addison’s Disease – Metabolic disorder

Student : Uzochukwu Adabanya Instructor : Prof. C ClowerInstitution : Clayton State University

What leads to this disorder?

Defects with the Adrenal glands (tuberculosis a common cause) chronic infections especially certain fungal infections invasion of the adrenal gland by cancer cells that have

spread from another part of the body especially the breast Cytomegalovirus (CMV) virus in association with AIDS-

causes birth defects Hemorrhage (bleeding) into the adrenals during shock- rare surgical removal of both adrenals other associated glands such as the thyroid and parathyroid

glands could also be defective as in polyendocrine deficiency syndrome (PDS)

All these Lead to adrenal glands not producing enough endogenous steroid hormones- mainly cortisol and aldosterone in some cases.

What leads to this disorder?

Cortisol- very important glucocorticoid Regulated by the hypothalamus and the pituitary gland maintains blood pressure and cardiovascular function slows the inflammatory response of the immune

system balances the effects of insulin in breaking down sugar

for energy helps regulate the metabolism of proteins,

carbohydrates, and fats helps maintain proper arousal and sense of well-being Glucocorticoids are distinguished from

mineralocorticoids and sex steroids by their specific receptors, target cells, and effects

What leads to this disorder?

Aldosterone- also important Minerocorticoid- hormones helping with salt and water

balance helps maintain blood pressure Helps with water and salt balance in the body by helping

the kidney retain sodium and excrete potassium Low levels of aldosterone lead to low blood volume and

low blood pressure due to loss of regulatory function of the hormone

Signs and Symptoms

weight loss muscle weakness Fatigue low blood pressure darkening of the skin in both exposed and nonexposed parts of the body in

certain instances marked cravings for salt or salty foods due to the urinary losses of sodium addisonian crisis- extreme cases

Do you think it is common?

Very rare Develops in both men and women of all ages Occurs in about 4 in every 100,000 people

Treatment

involves replacing or substituting the deficient hormones made by the adrenal glands

Standard therapy which involves the intravenous injections of substances such as hydrocortisone, saline (salt water), and dextrose (sugar). rapid improvement is commonly noticed

oral doses of fludrocortisone acetate in situations where aldosterone concentration is low

Surgery Patients with chronic adrenal insufficiency might need

surgery in extreme or critical situations. This could be done by administering injections of hydrocortisone and saline for general anesthesia.

References:

http://endocrine.niddk.nih.gov/pubs/addison/addison.htm#treatment

http://www.nadf.us/diseases/addisons.htm

Sigvald Bernhard RefsumSigvald Bernhard Refsum

• Occurs during lipid metabolism α-oxidation of Phytanic-Acid in the liver.

• Metabolic disruption is due to faulty enzyme

-Phytanoyl-CoA hydroxylase

• Causes excess buildup of Phytol (Phytanic-Acid) in the body plasma and tissue

• Very rare and an inherited disorder

• Leads to Neurological defects

where Myelin Sheath of neurons are damaged

• Neurologic damage• Cerebellar degeneration• Peripheral neuropathy(weakness Nausea)• Blindness• Ataxia• Scaly skin • Difficulty hearing• Cataracts• Epiphyseal dysplasia• Loss of smell

• Primary prevention for this disorder is a restrictive diet avoiding dairy products, beef, lamb, and fatty fish.

• Plasmapheresis- Filtering Blood for removal of Phytonic Acid (plasma exchange).

http://www.londonhospitals.ca/successes/renal.htm

• A.J. Wills, N.J. Manning and M.M. Reilly: Refsum's disease. Q J Med 2001; 94: 403-406

• "Health Minister Opens New Dialysis/Plasmapheresis Unit at Victoria Campus." London Health Science Centre. 23 Mar. 2001. St. Joseph's Healthcare London. 11 Nov. 2008 <http://www.londonhospitals.ca/successes/renal.htm>.

• "NINDS Refsum Disease Information Page." National Institute of Neurological Disorder and Stroke. 14 Feb. 2007. 6 Nov. 2008 <http://www.ninds.nih.gov/disorders/refsum /refsum.htm>.

• "Refsum Disease." 1 Aug. 2008. United Leukodystrophy Foundation. 6 Nov. 2008 <http://www.ulf.org/types/refsum.html>.

• "Refsum's disease." Wikipedia. 6 Nov. 2008 <http://en.wikipedia.org/wiki/refsum%27s_disease>.

Lesch-Nyhan Syndrome

Salwa Qadri

What is it?

• Genetic disorder

• X-linked recessive disease

• Rare

• Deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).

Metabolic process of HPRT

• Functions in recycling of purine bases hypoxanthine and guanine

• No salvage in absence of HPRT

• Speeds up synthesis of purines

• Failure of recycling process + increased synthesis of purine = overproduction of uric acid

Symptoms & Effects

• Severe gout, poor muscle control, and moderate retardation, which appear in the first year of life. 

• Neurological symptoms include facial grimacing, involuntary writhing, and repetitive movements of the arms and legs

• Self-mutilating behaviors – characterized by lip and finger biting – that begin in the second year of life.

Treatment

• Symptomatic

• Gout treated with allopurinol

• Kidney stones may be treated with lithotripsy

• No standard treatment for the neurological symptoms of LNS. 

• Death usually due to renal failure

Biochemistry IIKelly Ta

an inherited disorder - gene defect is an autosomal recessive genetic trait.

the body is unable to process certain proteins and lipids properly.

caused by an enzymatic defect in the oxidation of certain amino acids and lipids.

Mutation in the genes that coded for Methylmalonyl CoA mutase, the enzyme works with vitamin B12 to break down several amino acids, certain lipids, and cholesterol.

This condition occurs in an estimated 1 in 50,000 to 100,000 people.

Symptoms usually appear in early infancy and vary from mild to life-threatening.

Vomiting, dehydration, weak muscle tone, excessive tiredness, and failure to gain weight and grow at the expected rate.

Long-term effects include feeding problems, mental retardation, chronic kidney disease.

Without treatment, this disorder can lead to coma and death in some cases.

Treatment includes a carefully controlled diet, including a low-protein and/or restriction of isoleucine, valine, and threonine.

Medical food supplementation may be needed as well.

Wolman’s DiseaseWolman’s DiseaseBackgroundBackground

Autosomal Recessive (Rare)Autosomal Recessive (Rare)

Lipid storage DiseaseLipid storage Disease

Acid Lipase deficiencyAcid Lipase deficiency Lipid accumulation Lipid accumulation-Mutation in LIPA Gene-Mutation in LIPA Gene

SymptomsSymptoms

Hepatosplenomegaly

Umbilical Hernia

Hypotonia (low muscle tone)

Red blood cell

DiganosisDiganosis> 10% lysosomal Acid lipase> 10% lysosomal Acid lipase - Skin cell- Skin cell - Blood- Blood

Amiocentesis Amiocentesis

No treatment: “No treatment: “Bone Marrow TransplantBone Marrow Transplant””

ReferencesReferences1.1. National Institute of Neurological Disorder and stroke.National Institute of Neurological Disorder and stroke.

NNDS Acid Lipase Disease Information Page.NNDS Acid Lipase Disease Information Page.http://www.ninds.nih.gov/disorders/acid_lipase/acid_lipase.htm. http://www.ninds.nih.gov/disorders/acid_lipase/acid_lipase.htm.

2.2. W Krivit, Peter C et al 2000. Wolman disease successful treated by bone W Krivit, Peter C et al 2000. Wolman disease successful treated by bone marrow transplantation. marrow transplantation. Bone Marrow transplantation. 567-70.Bone Marrow transplantation. 567-70.

3. Images3. Imageswww.nlm.nih.gov/.../ency/fullsize/17215.jpgwww.nlm.nih.gov/.../ency/fullsize/17215.jpgfig.cox.miami.edu/Faculty/Dana/amniocentesis.jpg.fig.cox.miami.edu/Faculty/Dana/amniocentesis.jpg.ghr.nlm.nih.gov/dynamicImages/chromomap/lipa.jpegghr.nlm.nih.gov/dynamicImages/chromomap/lipa.jpeg

What is it?What is the defective process?

Metabolic processesSymptoms and Effects

How common is it?Can it be treated?

What is Tay-Sachs disease?

Inherited sickness caused by a build up of dangerous fat molecules. (brain and nerve tissue).

Ganglioside: GM2

Defective process Gene location: chromosome 15

Responsible for the production of an enzyme (Hex-A)

Cause: Insuficient activity of enzyme Beta hexoaminidase (Hex-A)

Metabolic process

Symptoms and effects

Children look normal up to six monthsRegression in developmentAt two years old: repeated seizures, inability

to crawl or roll over

At four Years old: Children nervous system affected resulting in death.

How common is Tay-sachs disease

Commonality of Tay-Sachs diseaseCommon in Eastern Europe

People of Ashkenzani People of Jewish descent U.S (1/27) Jewish are affected

Can Tay-Sachs disease be treated ?No treatment for Tay-Sachs diseaseMethods tried to cure Tay-Sachs disease

Enzyme hexoaminidase replacement Area of research: Gene Therapy

Ressources

Principles of Biochemistry, 4th ed. (David L. Nelson, Michael M. Cox

Concepts of Genetics, 8th ed. (Klug, Cumming, Spencer).

Genome.gov

What is it?

• Cystathionine beta synthase deficiency

• Inherited Disorder

• The body can not break down methionine in food

Defective Process

•CBS – Cystathionine Beta-Synthase Gene (control)

• Cystathionine Beta Synthase Enzyme

• Changes homocysteine to other compounds needed for the body

• Alteration to CBS gene- CBS enzyme goes down, homocystine builds up in the blood stream.

•Organs and tissues, including the eyes and the skeletal, vascular and central nervous systems

Metabolic Process

www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi

What are the symptoms and

effects?

• Visual problems

• Scoliosis

• Seizures

• Abnormal thinning

• Mental retardation

• Etc.

Common?

• 1 out of 335,000 people

worldwide

TREAMENTS ?

• No specific cure for homocystinuria.

• Medication/Diet

• Vitamin B6- reduce blood clotting & eye & bone problems

Sitosterolemia

Theresa Sihaphonh

Sitosterolemia

Sitosterolemia is inherited as a rare autosomal recessive disorder that leads to the hyperabsorption and decreased excretion of plant sterols

Mutation in ATP-binding cassette transporter (ABC transporter) proteins Plant sterols are not utilized by mammalian cells: fewer than 5

% are absorbed from GI tract and the rest is excreted by the liver

The sterols that do enter intestinal cells are pumped back out by ABC transporter proteins

Mutation = less hepatic secretion = less excretion in the liver = accumulation in cells

Sitosterolemia

Reduced whole-body cholesterol biosynthesis Reduced HMG-CoA reductase activity: rate-limiting

enzyme in cholesterol biosynthesis Increased LDL levels

Symptoms: tendon xanthomas & premature atherosclerosis

Rare disorder: only 45 cases worldwide Treatment: strict diet reducing intake of foods

rich in plant sterols (vegetable oil, olives, avocados)

By Hardik Modi

It is one of the 4 perioxisome biogenesis disorders (PBD)

Patients lack perioxisome

It is an inherited disorder

Defects in genes that are active in brain development and myelination

Elimination of perioxisomes

Lack of Perioxisomes causes lack of enzymes used in Beta-oxidation of fatty acids

Beta oxidation will not occur

Facial deformities High forehead, underdeveloped eyebrows,

deformed ear lobes.

Neurological abnormalities Mental retardation and seizures

Enlarged liver, Jaundice, gastrointenstinal bleeding.

Low muscle tone

1 of every 50,000 to 100,000 births

Affects males and females equally

It occurs at birth

No treatments are available

http://en.wikipedia.org/wiki/Zellweger_syndrome

http://www.ninds.nih.gov/disorders/zellweger/zellweger.htm

http://rarediseases.about.com/od/rarediseasesz/a/030505.htm

PorphyriasPorphyrias

CHEM 4203CHEM 4203Alysia GianiAlysia Giani

http://www.medmemoweb.com/Porphyria-cutanea-tarda.rea.gif

What is it?What is it? Group of disordersGroup of disorders

– Enzymes in Heme Enzymes in Heme biosynthetic pathwaybiosynthetic pathway

8 Enzymes8 Enzymes Affects skin Affects skin

(cutaneous), nervous (cutaneous), nervous system (Acute), or system (Acute), or Both.Both.– Hereditary coproporphyriaHereditary coproporphyria

– Variegate porphyriaVariegate porphyria Acquired or InheritedAcquired or Inherited

– Porphyria cutanea tardaPorphyria cutanea tarda

http://www.blc.arizona.edu/courses/bioc462b/grimes/nitrogen06/ch22/box-22-01.jpg

SymptomsSymptoms Three Major SymptomsThree Major Symptoms

– Abdominal PainAbdominal Pain– PhotodermatitisPhotodermatitis– Problems with nervous Problems with nervous

and muscular systemsand muscular systems Muscle pain/ weaknessMuscle pain/ weakness Personality changesPersonality changes Numbness/ TinglingNumbness/ Tingling

PrevalencePrevalence– 1 in 500 to 50,0001 in 500 to 50,000– 1 to 2 in 100,000 (PCT)1 to 2 in 100,000 (PCT)– 3 in 1,000 (VP)- 3 in 1,000 (VP)- Whites in Whites in

S. AfricaS. Africa

http://medimages.healthopedia.com/large/skin-porphyria.jpg

http://hjk880524.tripod.com/sitebuildercontent/sitebuilderpictures/phophyria.jpg

TreatmentTreatment TestsTests

– UrineUrine– PROTO blood testPROTO blood test

TreatmentTreatment– Hematin IVHematin IV– Pain medicationPain medication– SedativesSedatives– Propranolol Propranolol – OthersOthers

Beta-Carotene supplementBeta-Carotene supplement Removal of bloodRemoval of blood Higher carbohydrate intakeHigher carbohydrate intake

Interesting FactsInteresting Facts

VampiresVampires– Porphyrias Cutanea TardaPorphyrias Cutanea Tarda

http://www.hrp.org.uk/Images/George%20III_Copyright%20Historic%20Royal%20Palaces%2003.jpg

•King George III- Variegate Porphyrias

ReferencesReferences http://digestive.niddk.nih.gov/ddiseases/pubs/porphyria/http://digestive.niddk.nih.gov/ddiseases/pubs/porphyria/

index.htmindex.htm http://www.ghr.nlm.nih.gov/condition=porphyriahttp://www.ghr.nlm.nih.gov/condition=porphyria http://www.nlm.nih.gov/medlineplus/ency/article/http://www.nlm.nih.gov/medlineplus/ency/article/

001208.htm001208.htm http://www.porphyriafoundation.com/about_por/history.htmlhttp://www.porphyriafoundation.com/about_por/history.html

Argininosuccinic Acidemia

Urea Cycle disorder

Victims of this disease can not convert ammonia into urea to be excreted from the body.

Argininosuccinate created in the urea cycle is missing the enzyme argininosuccinase (argininosuccinic lyase)to cleave it.

http://www.carolguze.com/text/442-11-clinical_genetics.shtml

http://j2k.naver.com/j2k.php/japan/www.answers.com/topic/argininosuccinic-aciduria

Symptoms– Lack of appetite, vomiting, restlessness, seizures, brain

damage, coma and death.

Treatment– Low protein diets, arginine supplementaion and in some

cases dialysis.

Frequency– 1 of every 70,000 live births will have some form of ASA.

"Amino Acid Disorders." www.newbornscreening.info September 31, 2006 1-11. 11 Nov 2008 <http://www.newbornscreening.info/Parents/aminoaciddisorders/ASAL.pdf>.

"Argininosuccinic aciduria." Genetics Home Reference Mar 2007 09 Nov 2008 <http://ghr.nlm.nih.gov/condition=argininosuccinicaciduria>.

Monique M. Nurse

Biochemistry

11/11/08

Nonketotic Hyperglycinemia (NKH)

aka glycine encephalopathy Autosomal recessive hereditary metabolic

disorder affects the breakdown of the amino acid glycine in

infants Characterized by abnormally high levels of the

amino acid glycine in the blood, urine, and the cerebrospinal fluid.

cause extensive neuronal damage in neonatal brain via N-methyl-D-aspartate glutamate receptor-mediated

Where does it occur?

Glycine Cleavage System (GCS) a multi-enzyme complex composed of four

different protein components P-protein (glycine dehydrogenase), T-protein (catalyses a methyl group to

tetrahydrofolate), H-protein (aminomethyl carrier) L-protein (normal)

• Mutations in P-, T-, and H-proteins are responsible for nonketotic hyperglycinemia.

What is affected?

Glycine Cleavage System mutation in the GCS

inadequate supply of the enzymes necessary to the break down of glycine causing a build up of glycine in the body.

• The AMT and GLDC genes

Fig. infant brain with NKH

Symptoms and Effects

Four forms of this disorder:

Neonatal form seen in the first few days after birth

low muscle tone (hypotonia), and drowsiness seizures and mental retardation

Infantile form six months of seemingly normal development

with the exception of occasional feeding difficulties & seizures varying degrees of mental retardation become evident.

Symptoms and Effects CONT.

Mild-episodic form appears during childhood episodes of delirium;

involuntary, jerky movements (chorea); inability to look upward (vertical gaze palsy)

fever and mild mental retardation

Late-onset form during childhood with progressive stiffness in

both legs and degeneration of the optic nerve, leading to loss of sight.

Neither seizures nor mental retardation are associated

How common is NKH?

Rare metabolic disorder that usually affects infants soon after birth. Estimated 1 in 60,000

Males & females appear to be affected in equal proportions.

Both parents are carriers 25% chance child will be born with

the disease 50% chance child will be a carrier for

the gene defect.

Can it be treated? How?

At this time there are no existing treatments. Rarely children grow out of NKH and go on

to live normal lives.

For some individuals glycine levels have decreased but mental retardation and seizures may still persist.

Tarui’s DiseaseTarui’s Disease

Tarui’s DiseaseTarui’s Disease

Gylcogen storage diseaseGylcogen storage disease Phosphofructokinase deficiency Phosphofructokinase deficiency

Glycolysis Glycolysis

Glyconeogenesis metabolism slowsGlyconeogenesis metabolism slows Glycogen buildup Glycogen buildup

Tarui’s DiseaseTarui’s Disease

Organ Affected Organ Affected ErythrocytesErythrocytes MusclesMuscles

Symptoms Symptoms Exercise-induced fatigueExercise-induced fatigue Muscle PainMuscle Pain Hemolytic Anemia Hemolytic Anemia Myoglobin in urinMyoglobin in urin Jaundice Jaundice

Tarui’s Disease Tarui’s Disease

Affects 2.3 children per 100,000 births per Affects 2.3 children per 100,000 births per yearyear

Disease present itself during early childhoodDisease present itself during early childhood Inherited autosomal recessive conditionInherited autosomal recessive condition Appears to be prevalent among people of Appears to be prevalent among people of

Ashkenazi Jewish decentAshkenazi Jewish decent

Tarui’s Disease Tarui’s Disease

No Treatment or CureNo Treatment or Cure

Diet ManagementDiet Management High Fat ContentHigh Fat Content

May not be effectiveMay not be effective

Liver TransplantationLiver Transplantation Abolish biochemical abnormalitiesAbolish biochemical abnormalities

References References

Anderson, W. E. (2007). Anderson, W. E. (2007). Glycogen Storage Disease, Glycogen Storage Disease, Type VIIType VII. Retrieved November 10, 2008, from . Retrieved November 10, 2008, from http://www.emedicine.com/med/topic913.htm.http://www.emedicine.com/med/topic913.htm.

Mallery, C. Mallery, C. PFK-1PFK-1. Retrieved November 10, 2008, . Retrieved November 10, 2008, from from http://porpax.bio.miami.edu/~cmallery/255/255atp/mhttp://porpax.bio.miami.edu/~cmallery/255/255atp/mcb8.12.PFK.jpg cb8.12.PFK.jpg

Nelson, D. L., & Cox, M. M. (2008). Nelson, D. L., & Cox, M. M. (2008). Principles of Principles of BiochemistryBiochemistry. New York: W. H. Freeman and . New York: W. H. Freeman and Company. Company.

Favism

A condition caused by accumulation of hydrogen peroxide and hemolytic anemia

- destruction of red blood cells

Symptoms

• Fever

• Nausea

• Abnormal pain and headaches

• Anemic conditions

• Pallor

- reduced a mount of oxyhemoglobin on skin.

Causes of Favism

• Exposure to pollen of fava plants

• Eating fava beans

• Deficiency of Glucose-6-Phosphate Dehydrogenase

It is common around countries in the Middle East and Mediterranean

Fava Beans• Glycosides vicine andConvicine - depletion of Glutathione

• main commercial source of the drug L-dopa - converted to dopamine in the brain

• L-dopa is found in food and made from tyrosine in humans

G6PD

• Glucose-6-phosphate dehydrogenase

• Involved in the pentose phosphate pathway.

• Supplies cells such as RBCs with energy by maintaining the level of NADPH

• NADPH regulates the amount of glutathione because the tripeptide protects red blood cells from oxidative damage.

- regulation of peroxide accumulation

Who is at risk?

• Deficiency of the enzyme glucose-6 phosphate dehydrogenase is an X-linked genetic trait.

• Men versus women

• Breastfeeding infants

• Treatment involved blood transfusion

Sources

• www.adam.com

• Principles of Biochemistry by Lehninger, Nelson, and Cox, 4th ed. (2005) or 5th ed. (2008), W. H. Freeman and Co.

By Laurie Brier

Phenylketonuria (PKU)

Autosomal recessive

Normal catabolism of phenylalanine →

Defective phenylalanine hydroxylase (PAH)

Alternative pathway High levels of

phenylalanine and phenylpyruvate

Phenylpyruvate is decarboxylized into phenylacetate

Odorhttp://www.uic.edu/classes/phar/phar332/Clinical_Cases/aa%20metab%20cases/PKU%20Cases/PKU%20biochem%20intro.htm

Defective dihydrobiopterin reductase Regenerates tetrabiopterin

cofactor of phenylanine hydroxylase L-Dopa and 5-HTP

Epilepsy and mental retardation 10 in 100,000 newborns diagnosed

yearly

Early detection Screen for disease and type Treatment

Low protein diet (PAH)+ L-Dopa and 5-HTP (dihydrobiopterin

reductase)

Alkaptonuria Alkaptonuria black urine diseaseblack urine disease

By Corney CrumbleyBy Corney Crumbley

Alkaptonuria that sounds like a Alkaptonuria that sounds like a diseasedisease

This disease is and rare autosomal This disease is and rare autosomal recessive condition.recessive condition.

The disease is due to the inablilty to The disease is due to the inablilty to properly metablizing tyrosineproperly metablizing tyrosine

This allows for the build up for toxic This allows for the build up for toxic tyrosine by product Homogentisic tyrosine by product Homogentisic acid. acid.

Why enzyme Why?Why enzyme Why? The enzyme homogentisate 1,2-dioxygenase, The enzyme homogentisate 1,2-dioxygenase,

which is involved in the break down of aromatic which is involved in the break down of aromatic rings such as tyrosine does not work.rings such as tyrosine does not work.

The metabolic process that is effected is The The metabolic process that is effected is The degrading of Tyrosine to Fumarate is effected at degrading of Tyrosine to Fumarate is effected at step three where Homogentisate to 4 step three where Homogentisate to 4 Maleylacetoacetate.Maleylacetoacetate.

Where does it Hurt Where does it Hurt Some of the symptoms are Some of the symptoms are

sclera of the eyes may be sclera of the eyes may be pigmented (later age) pigmented (later age)

Sweat may turn brown as well Sweat may turn brown as well as standing urine which is as standing urine which is noticed in babiesnoticed in babies

Kidney stones and stones in Kidney stones and stones in the prostate in men are the prostate in men are common common

The effects are mostly due to The effects are mostly due to Homogentisic acid in tissuesHomogentisic acid in tissues..

Once in the joints it can lead Once in the joints it can lead to cartilage damage mostly in to cartilage damage mostly in the spine leading to lower the spine leading to lower back pain. Joint a replacement back pain. Joint a replacement is often necessary at young is often necessary at young age age

Dude once there is no coming backDude once there is no coming back

This disease is common in Slovakia and This disease is common in Slovakia and Dominican Republic Dominican Republic

Less than 1 in 250000 are effected by this Less than 1 in 250000 are effected by this disease. disease.

There is no cures but only treatments There is no cures but only treatments Restriction of Phenylalanine, tyrosine, Restriction of Phenylalanine, tyrosine,

vitamin Cvitamin C The insecticide nitisinone which serves as The insecticide nitisinone which serves as

an inhibitor in the production of an inhibitor in the production of Homogentisic acid from 4-Homogentisic acid from 4-hydroxyphenylpyurvic acid.hydroxyphenylpyurvic acid.

Thank you Thank you