Showing posts with label Metabolism. Show all posts
Showing posts with label Metabolism. Show all posts

15 March 2016

Metabolic pathways



Metabolic pathways

Metabolism and Cell Structure
http://faculty.chemeketa.edu/

metabolic pathway
http://www.centralia.edu

Metabolic Processes
Enzymes, Energy and Chemical Reactions
http://faculty.mwsu.edu

Introduction to Metabolism
http://www.valdosta.edu

Introduction to Metabolism
http://www.ag.unr.edu/

Energy and Metabolism
http://www.austincc.edu

Metabolism
http://chemistry.creighton.edu

Metabolic Pathways and Energy Production
http://sp.myconcorde.edu

Chemotrophic Energy Metabolism: Glycolysis and Fermentation
http://www.clayton.edu/

Pathway Bioinformatics (2)
Peter D. Karp, PhD
http://www.bibalex.org

Essentials of Metabolism
http://academicdepartments.musc.edu/

An Introduction to Metabolism
Chris Romero
http://www.barstow.k12.ca.us/

Metabolic/Subsystem Reconstruction and Modeling
http://akka.genetics.wisc.edu

Your Body’s Metabolism
http://iws.collin.edu/

500 Published articles of Metabolic pathways

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04 June 2012

Purine metabolism



Nucleotides, Purine Biosynthesis and Purine Catabolism
Purine Catabolism.ppt

Clinical Pharmacology - Drug Therapy of Gout
Reginald D Sanders, MD
Gout Pharmacology.ppt

Amino Acid Biosynthesis
MetabolismIII.ppt

The biosynthetic origins of purine ring atoms
Nucleotide_metabolism.ppt

Biosynthesis of nucleotides
Natalia Tretyakova, Ph.D.
Lectures1and2.ppt

Arthritis of the Hands
Arthritis of the Hands.ppt

Immunosuppresseive agents
Dr. Prakash Nagarkatti
Immunosuppresseive agents.ppt

Non-specific immunosuppressants
Non-specific immunosuppressants.ppt

Diseases that Affect the Kidney and Urinary Tract
Nancy Long Sieber, Ph.D
Diseases that Affect the Kidney and Urinary Tract.ppt

Rhabdomyolysis
Rhabdomyolysis.ppt

renal failure in multiple myeloma
Myeloma.ppt

Metabolism of Purine and Pyrimidine Nucleotides
Metabolism of Purine and Pyrimidine Nucleotides.ppt

Lesch-Nyhan Disease
By: Lindsey Kost
Lesch-Nyhan Disease.ppt

Gout
Wayne Blount, MD, MPH
GOUT.ppt

Purine Metabolism/Diseases
Raymond B. Birge
Purine Metabolism/Diseases.ppt

74 full text articles free access

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06 May 2012

Malabsorption Syndromes



Carbohydrate- & Fat-Modified Diets for Malabsorption
Carbohydrate- & Fat-Modified Diets for Malabsorption.ppt

Disorders of the Small Bowel
Disorders of the Small Bowel.ppt

Diverticulosis and Diverticulitis
Diverticulosis and Diverticulitis.ppt

Vitamin Deficiency Disorders
Vitamin Deficiency Disorders.ppt

Conditions of Malabsorption
Conditions of Malabsorption.ppt

Gastrointestinal System nutrition
S. Buckley, RN, MS
Gastrointestinal System nutrition.ppt

Iron Deficiency Anemia Building Blocks of Life
FeDef-Agoglia.ppt

Nutrition and Lower Gastrointestinal Disorders
Lower Gastrointestinal.ppt

Secretions of Digestion
Secretions of Digestion.ppt

Pediatric Gastroenterology
Pediatric Gastroenterology.ppt

Diseases of the Gastrointestinal Tract
Diseases of the Gastrointestinal Tract.ppt
42 Free full text articles

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11 March 2012

Metabolic Acidosis



Arterial Blood Gas Analysis
Vanessa Klee MSIV
AGBpresentation.ppt

Acid-Base Disorders and the ABG
Acid-Base/Acid-Base.ppt

Interpretation: Compensated and Uncompensated Blood Gas Analysis
James Barnett, RN, MSN
Interpretation_Comp_and_Uncomp_Blood_Gas_Analysis.ppt

Approach to Inborn Errors of Metabolism
Andrew M. Ellefson MD
IEM_Ellefson.ppt

Acid and Base Balance and Imbalance
http://www.clt.astate.edu/Acid and Base Balance and Imbalance.ppt

Case Studies on Acid-Base Disorders
William T. Browne, M.D.
Case Studies on Acid-Base Disorders.ppt

Approach to Inborn Error of Metabolism in a Neonate
Filomena Hazel R. Villa, MD
Dr_Villa-_PL-2.ppt

Renal Tubular Acidosis
Kathleen Wren
RTA.ppt

Metabolic acidosis
Anne Peery, MD
Metabolic acidosis.ppt

Acid – Base Disorders
Viyeka Sethi
Acid – Base Disorders.ppt

Acid Base Balance and Fluid Balance
Dr. Kathleen Ethridge
AcidBaseBalanceFluidBalance.ppt

Acid-Base Disturbances Clinical Approach
Pravit Cadnapaphornchai
Acid-Base Disturbances.ppt
Latest 50 published articles

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10 March 2012

Purine metabolism inhibitors



Nucleic Acid  Metabolism
Nucleic Acid  Metabolism.ppt

Overview of Amino Acid Metabolism
Amino Acid Metabolism.ppt

Nucleotides: Synthesis and Degradation
Nucleotides_revised.ppt

Non protein  nitrogen compounds metabolism
Metabolism%201386.ppt

Metabolic Pathways
metabolism.ppt

Amino Acid Metabolism-One-carbon  metabolism, purine metabolism
Purine  metabolism.ppt

Purine  metabolism (Overview)
Gihan E-H Gawish, MSc, PhD
Purine  metabolism.ppt

Anticancer Agents Protein  Kinase Inhibitors
Anticancer Agents Protein  Kinase Inhibitors.ppt

Biosynthesis  and Degradation of Nucleotides
Baynes  & Dominiczak, Gene C. Lavers,  Ph.D.
BDN.ppt

Pharmacological  aspects of renal transplant  immunosuppression
Paediatric  Nephrology Trainees Meeting - Mark  Lee
Paediatric  Nephrology Trainees Meeting.ppt

Nucleotide metabolism
Lecture26.ppt

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05 February 2012

Primary amyloidosis Ppts latest 50 Published articles



Primary amyloidosis: Primary amyloidosis is a disorder in which abnormal proteins build up in tissues and organs. Clumps of the abnormal proteins are called amyloid deposits.

Primary amyloidosis can lead to conditions that include:
    Carpal tunnel syndrome
    Heart muscle damage (cardiomyopathy) leading to congestive heart failure
    Intestinal malabsorption
    Liver enlargement
    Kidney failure
    Nephrotic syndrome
    Neuropathy (nerves that do not work properly)
    Orthostatic hypotension (abnormal drop in blood pressure with standing)

Primary  AL Amyloidosis
by Matthew  Volk
http://www.med.unc.edu/medicine/web/12.1.08%20Volk.%20Amyloid,%20LCDD.ppt

Cardiac  Amyloidosis
by Ann Isaksen
https://medicine.med.unc.edu/education/internal-medicine-residency-program/files/ppt/11.10.09%20Isaksen%20cardiac%20amyloid.ppt

Primary  Amyloidosis  Case Presentation & Discussion
By Warren  Brenner
http://hematology.wustl.edu/conferences/presentations/Brenner20031017.ppt

Immune Disorders:  HLA and Disease Associations and Amyloidosis
by Nancy L. Jones, M.D.
http://cmspath.edu/rfc/lectures11-12/jones/hla/jones-hla_and_amyloidosis.ppt

Protein  Structure Determination, Protein Folding, Molecular Chaperones, Prions Alzyheimer’s
http://www.uh.edu/sibs/faculty/glegge/lecture_18.ppt

Computational  Method for Predicting Amyloidogenic Sequences
by Bill Welsh
http://dimacs.rutgers.edu/Workshops/Neurodegenerative/slides/welsh.ppt

Alphabet  Soup and Interstitial Lung Disease
by Leslie  Scheunemann
http://www.med.unc.edu/medicine/web/3.26.08%20ILD%20Scheunemann.ppt

Latest 50 Published articles:

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28 January 2012

Phenylketonuria (PKU) - Video



If you have Phenylketonuria (PKU) (Imbecillitas phenylpyruvica, as it was formerly known), you MUST avoid Aspartame (NutraSweet). Persons with the genetic disorder phenylketonuria (PKU) cannot metabolize phenylalanine. This leads to dangerously high levels of phenylalanine in the brain (sometimes lethal). It has been shown that ingesting aspartame, especially along with carbohydrates, can lead to excess levels of phenylalanine in the brain even in persons who do not have PKU. Aspartame is 40% phenylalanine.

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01 September 2011

Maple syrup urine disease Presentations



Maple syrup urine disease (MSUD) is a metabolism disorder passed down through families in which the body cannot break down certain parts of proteins. Urine in persons with this condition can smell like maple syrup.

Maple syrup urine disease (MSUD) is caused by a gene defect. Persons with this condition cannot break down the amino acids leucine, isoleucine, and valine. This leads to a buildup of these chemicals in the blood.

In the most severe form, MSUD can damage the brain during times of physical stress (such as infection, fever, or not eating for a long time).

Some types of MSUD are mild or come and go. Even in the mildest form, repeated periods of physical stress can cause mental retardation and high levels of leucine.

Metabolism
by Eric Niederhoffer
http://www.siumed.edu/~eniederhoffer/som_pbl/SSB/powerpoint/metabolism%20in%20muscle_nerves.ppt

Newborn Screening in Washington
by Cristine M Trahms, MS, RD, FADA
http://courses.washington.edu/nutr526/lectures/NBS_05.ppt

Clinical Chemistry Amino Acids & Proteins
by Keri Brophy-Martinez
http://www.austincc.edu/mlt/chem/proteins_overview_2011_STUDENT.ppt

Urinalysis
http://www.austincc.edu/mlt/ua/uaUrinalyisisReview.ppt

Infant Nutrition: Conditions & Interventions
http://www.cwu.edu/~bergmane/nutr545/Powerpoint/Infant%20Nutrition(ch9%20brown).ppt

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15 July 2011

Hyperlipidemia 12 Presentations



Hyperlipidemia 12 Presentations
Hyperlipidemia, Hypertension, and Diabetes
http://www.longwood.edu/staff/roycj/Hyperlipidemia.ppt


Hyperlipidemia by Michele Ritter, M.D
http://www9.georgetown.edu/faculty/wheltosa/Shelly_Hyperlipidemia.ppt


Hypertension, Hyperlipidemia: Are our children safe? by Patrick R
http://www9.georgetown.edu/faculty/wheltosa/Saleeb-HTN,_Lipids_(ATP_III).ppt

New Nutritional Approaches for the Treatment of Hyperlipidemia by Laura S. Kinzel, M.S., R.D
http://www.pitt.edu/~super7/PC/pc0041.ppt

Thyroid Disorders and Hyperlipidemia by Uzma Khan M.D.
http://imed.missouri.edu/immse/Y3/conference_handouts/management/M3lip-thyroid907.ppt

Hyper(dys)lipidemias: Disorders of Lipoprotein Metabolism by Michael J. Caplan
http://www.musc.edu/comyear2/BLOCK4/ASF/26-Hyperlipidemia%5B1%5D_MJC_modified_11-23-10.ppt

Lipid Transport: Lipoprotein Structure, Function, and Metabolism
http://www.cwu.edu/~geed/543/Lipid%20Transport.ppt

Primary Care Approach to Dyslipidemia by David Thom, MD, PhD
http://sfghdean.ucsf.edu/barnett/FCM/PGY1/0502_Hyperlipidemia.ppt

Dyslipidemia and Atherosclerosis by Eliot A. Brinton, M.D.
http://umed.med.utah.edu/ms2008/Vault/Cardio/OSLecture8-12-7-05.ppt

Antihyperlipidemic Drugs
http://www.coastalbend.edu/Occu/Nursing/olma/pharmacology/spring%202010/Ch%2035.ppt

Drugs for Lipid Disorders
http://www.mac.edu/faculty/ChristineStaake/Nursing%20311/Web%20Drugs%20for%20Lipid%20Disorders.ppt

Dyslipidemia
http://www.longwood.edu/staff/roycj/EIDdyslipidemia.ppt

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21 May 2010

Hyponatremia and Hypernatremia



Hyponatremia and Hypernatremia
By:Conor Gough, HO – III

Hyponatremia
* Defined as sodium concentration < 135 mEq/L * Generally considered a disorder of water as opposed to disorder of salt * Results from increased water retention * Normal physiologic measures allow a person to excrete up to 10 liters of water per day which protects against hyponatremia * Thus, in most cases, some impairment of renal excretion of water is present Causes * Normal ADH response to low sodium is to be suppressed to allow maximally dilute urine to be excreted thereby raising serum sodium level * Psuedohyponatremia – High blood sugar (DKA) or protein level (multiple myeloma) can cause falsely depressed sodium levels * Causes of Hyponatremia can be classified based on either volume status or ADH level o Hypovolemic, Euvolemic or Hypervolemic o ADH inappropriately elevated or appropriately suppressed ADH suppresion ADH elevation
First step in Assessment: Are symptoms present?
* Hyponatremia can be asymptomatic and found by routine lab testing
* It may present with mild symptoms such as nausea and malaise (earliest) or headache and lethargy
* Or it may present with more severe symptoms such as seizures, coma or respiratory arrest

Presentation determines if immediate action is needed
* If severe symptoms are present, hypertonic saline needs to be administered to prevent further decline
* If severe symptoms are not present, can start by initiating fluid restriction and determining cause of hyponatremia
* Oral fluid restriction is good first step as it will prevent further drop in sodium
* NOTE: This does not mean that you can’t give isotonic fluids to someone who is truly volume depleted

WHAT NEXT?
* With no severe symptoms and fluid restriction started, next step is to assess volume status to help determine cause
* Hypovolemic – urine output, dry mucous membranes, sunken eyes
* Euvolemic – normal appearing
* Hypervolemic – Edema, past medical history, Jaundice (cirrhosis), S3 (CHF)

Volume status helps predict cause
* Hypovolemia
o True Volume Depletion
o Adrenal insufficiency
o Thiazide overdose
o Exercised induced hyponatremia
* Euvolemia
o SIADH
o Primary Polydipsia
* Hypervolemia
o Cirrhosis and CHF

Workup for Hyponatremia
How to interpret the tests?
* Serum Osmolality
o Can differentiate between true hyponatremia, pseudohyponatremia and hypertonic hyponatremia
* Urine Osmolality
o Can differentiate between primary polydipsia and impaired free water excretion
* Urine Sodium concentration
o Can differentiate between hypovolemia hyponatremia and SIADH

Additional Tests
* TSH – high in hypothyroidism
* Cortisol – low in adrenal insufficiency, though may be inappropriately normal in infection/stressful state, therefore should get Corti-Stim test to confirm
* Head CT and Chest Xray – May see evidence of cerebral salt wasting or small cell carcinoma which can both cause hyponatremia
* Iatrogenic infusion of hypotonic fluids (“Surgeon sign”)
* Ecstasy use – increased water intake with inappropriate ADH secretion
* Underlying infections
* NSIAD – Nephrogenic syndrome of inappropriate antidiuresis – Hereditary disorder that presents with low sodium levels in newborn males with undetectable ADH levels
* Reset Osmostat – Occurs in elderly and pregnancy where regulated sodium set point is lowered

SIADH: Important concept to understand
Main diagnostic criteria for SIADH
Treatment is based on symptoms
Severe symptoms present
What if little to no symptoms are present?
Formulas that may help: How much sodium does the patient need?
* Sodium deficit = Total body water x (desired Na – actual Na)
* Total body water is estimated as lean body weight x 0.5 for women or 0.6 for men

How about an example:
What if the sodium increases too fast?
Risk Factors for demyelination
Treatment Options
Summary of Hyponatremia
Moving on to Hypernatremia
Causes of Hypernatremia
Symptoms of Hypernatremia
Diagnosis of Hypernatremia
Treatment of Hypernatremia
Summary of Hypernatremia

Hyponatremia and Hypernatremia.ppt

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21 April 2010

Lipids



Lipids
By: Henry Wormser, Ph.D.

Introduction
* Definition: water insoluble compounds
+ Most lipids are fatty acids or ester of fatty acid
+ They are soluble in non-polar solvents such as petroleum ether, benzene, chloroform
* Functions
+ Energy storage
+ Structure of cell membranes
+ Thermal blanket and cushion
+ Precursors of hormones (steroids and prostaglandins)
* Types:
+ Fatty acids
+ Neutral lipids
+ Phospholipids and other lipids
Fatty acids
* Carboxylic acid derivatives of long chain hydrocarbons
o Nomenclature (somewhat confusing)
+ Stearate – stearic acid – C18:0 – n-octadecanoic acid
o General structure:
* Common fatty acids
n = 4 butyric acid (butanoic acid)
n = 6 caproic acid (hexanoic acid)
n = 8 caprylic acid (octanoic acid)
n = 10 capric acid (decanoic acid)
* common FA’s:

n = 12: lauric acid (n-dodecanoic acid; C12:0)
n = 14: myristic acid (n-tetradecanoic acid; C14:0)
n = 16: palmitic acid (n-hexadecanoic acid; C16:0)
n = 18; stearic acid (n-octadecanoic acid; C18:0)
n = 20; arachidic (eicosanoic acid; C20:0)
n= 22; behenic acid
n = 24; lignoceric acid
n = 26; cerotic acid

Less common fatty acids
* iso – isobutyric acid
* anteiso
* odd carbon fatty acid – propionic acid
* hydroxy fatty acids – ricinoleic acid, dihydroxystearic acid, cerebronic acid
* cyclic fatty acids – hydnocarpic, chaulmoogric acid

PHYTANIC ACID
A plant derived fatty acid with 16 carbons and branches at C 3, C7, C11 and C15. Present in dairy products and ruminant fats.
A peroxisome responsible for the metabolism of phytanic acid is defective in some individuals. This leads to a disease called Refsum’s disease
Refsum’s disease is characterized by peripheral polyneuropathy, cerebellar ataxia and retinitis pigmentosa
Less common fatty acids
These are alkyne fatty acids
Fatty acids
* Fatty acids can be classified either as:
o saturated or unsaturated
o according to chain length:
Unsaturated fatty acids
* Monoenoic acid (monounsaturated)
Double bond is always cis in natural fatty acids.
This lowers the melting point due to “kink” in the chain
* Dienoic acid: linoleic acid
* Various conventions are in use for indicating the number and position of the double bond(s)
* Polyenoic acid (polyunsaturated)
* Monoenoic acids (one double bond):
* Trienoic acids (3 double bonds)
* Tetraenoic acids (4 double bonds)
* Pentaenoic acid (5 double bonds)
* Hexaenoic acid (6 double bonds)
Both FAs are found in cold water fish oils
Typical fish oil supplements
Properties of fats and oils
* fats are solids or semi solids
* oils are liquids
* melting points and boiling points are not usually sharp (most fats/oils are mixtures)
* when shaken with water, oils tend to emulsify
* pure fats and oils are colorless and odorless (color and odor is always a result of contaminants) – i.e. butter (bacteria give flavor, carotene gives color)
Examples of oils
* Olive oil – from Oleo europa (olive tree)
* Corn oil – from Zea mays
* Peanut oil – from Arachis hypogaea
* Cottonseed oil – from Gossypium
* Sesame oil – from Sesamum indicum
* Linseed oil – from Linum usitatissimum
* Sunflower seed oil – from Helianthus annuus
* Rapeseed oil – from Brassica rapa
* Coconut oil – from Cocos nucifera.....


Websites on lipids

* http://www.cyberlipid.org/ web site deals mainly with an overview on all lipids
* http://www.lipidsonline.org – this website focuses mainly on disease processes (atherosclerosis) and treatment
* http://www.lipidlibrary.co.uk/ -There are two main divisions in this website, one dealing with the chemistry and biochemistry of lipids and the other with the analysis of lipids


Lipids.ppt

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Inborn Errors of Metabolism



Inborn Errors of Metabolism
By:Namrata Singh M.D

Introduction to IEM
* Usually a single gene defect that causes a block in metabolic pathways.
* Problems are because of accumulation of enzyme substrate behind the metabolic block or deficiency of the reaction product.
* In some instances the substrate is diffusible & affects distant organs & in some there is just a local effect ( lysosomal storage disease ).
* Clinical presentation is varied  mild to severe forms ( mutations even in the same gene may be different in different people ).
* Can present at any time.
* Can affect any organ system.

IEM General approach
* DIAGNOSIS : Some clinical presentations:-
o Consider in DDx . when dealing with :-
+ Critically ill infant
+ Seizures
+ Encephalopathy (Reyes like syndrome )
+ Liver disease
+ MR or developmental delay or regression
+ Recurrent vomiting
+ Unusual odor
+ Unexplained acidosis
+ Hyperammonemia
+ hypoglycemia
* Some clues to look for :-
o *Symptoms accompany changes in diet.
o *Developmental regression.
o *History of food preferences or aversions.
o *History of consanguinity in parents.
o *Family history of MR , unexplained deaths in cousins or siblings etc.
* Physical exam:- common findings—
o Alopecia or abnormal hair
o Retinal cherry red spot
o Cataracts or corneal opacities
o Hepatosplenomegaly
o Coarse features
o Skeletal changes ( gibbus)
o Ataxia
o FTT
o Micro or macrocephaly
o Rash / jaundice /hypo or hypertonia
* Lab tests:- almost always needed—
o Serum electrolytes
o Ph ( anion gap & acidosis )
o Se lactate
o Se pyruvate
o Ammonia
o Serum & urine amino acids
o Urine organic acids
o DNA probes
o Glycine in CSF (glycine encephalopathy)
o Urine ketones
+ If + in neonates  IEM
+ If – in older child  IEM ( defect in f.a. oxidation )

IEM – Clinical situations
* MR or dev delay
o Can occur alone.
o Seen in urea cycle ,a.a disorders.
o Also in organic acidemias ,peroxisomal & lysosomal storage disorders.
o Serum & urine a.a .
o Urine for mucopolysacchiduria.
* Ill neonate :-
o Clinically indistinguishable from sepsis.
o Usually disorders of protein & CHO metabolism.
o Acidosis or altered mental status out of proportion to systemic symptoms.
o Labs:
+ Lytes , NH3, gluc , ketones , urine ph ,glycine in CSF.
+ Se & urine for a.a & o.a (* before oral intake is stopped or pt is transfused)

IEM – Clinical situations
* Vomiting & encephalopathy :-
* Hypoglycemia :-
o Seen in fatty acid oxid defects ,glycogen storage diseases ,hereditary fructose intolerance & organic acidemias.
o Other labs:-
Urine ketones ~(+) in GSD & organic acidemias. ~(-) in HFI & f.a. oxidation disorders
o Other labs:-
+ NH3 elevated in organic acidemias & fatty acid oxidation defects.
+ Urine reducing subst.– (+) in galactosemia ,HFI.
+ Urine organic acids
* Hyperammonemia :-
o initially – poor appetite , irritability . Then , vomiting , lethargy , seizures & coma.
o Tachypnea – direct effect on resp. drive.
o Seen in (1)- urea cycle disorders (2)- organic acidemias (3)- transient hyperammonemia of the newborn.
o Resp alkalosis : urea cycle disorders & transient hyperammonemia of newborn.
o Acidosis : organic acidemias

RESP ALKALOSIS
ACIDOSIS
UREA CYCLE DEFECTS
TRANSIENT HYPERAMMONEMIA OF NEWBORN
ORGANIC ACIDEMIAS
SE CITRULLINE—LOW– EARLY UREA CYCLE DEFECT
SLIGHTLY ELEV– TRANSIENT HYPERAMMONEMIA OF NB
MARKEDLY ELEV– CITRULLINEMIA & ARGINOSUCCINIC ACIDEMIA
* Acidosis :-
o With recurrent vomiting.
o With elevated NH3.
o Out of proportion to clinical picture.
o Difficult to correct.
o Seen in organic acidemias , MSUD ,GSD , disorders of gluconeogenesis.
o Increased anion gap (ketoacids ,lactic acid , methylmalonic acid.)

* Acidosis :- additional tests—
o Se glucose
o NH3
o Urine pH
o Ketones
o Amino & organic acids
o Blood lactate & pyruvate
* Lactate & pyruvate—
o Measure in arterial blood.
o Normal Ratio is 10:1 to 20:1.
o High ratio
+ Mitochondrial disorders.
+ Pyruvate carboxylase deficiency.
o Normal or low ratio
+ Glycogen storage disease.
+ Pyruvate dehydrogenase deficiency
* Broad management :-
o Problems severe acidosis , hypoglycemia , hyperammonemia . Can lead to coma & death!
o Stop all oral intake.
o Give I/V glucose to stop catabolism.( most respond favorably to glucose – some do not eg. Primary lactic acidosis in pyruvate dehydrogenase deficiency .)
o Bicarb.
o Hyperammonemia – may need dialysis .
* Specific interventions :-
o Urea cycle disorders-
+ * preventing protein catabolism ( high calorie diet , arginine supplementation )
+ * decreasing NH3 load (protein restriction )
+ * utilizing NH3 scavengers ( benzoate ,phenylbutyrate)
o PKU-
+ *Avoid enzyme substrate in diet.
+ *Diet low in phenylalanine ( Lofenelac , Phenylfree, Analog XP , Maxamaid XP )
+ *Protein restriction.
o Galactosemia-
+ *galactose free diet ( soy formulas contain sucrose rather than lactose )
o Isovaleric acidemia-
+ Pharmacotherapy to remove accumulated substrate –( glycine treatment).
o Methylmalonic acidemia-
+ Provide co-enzyme ( vit B12)
o Gauchers disease-
+ Provide normal enzyme (enzyme infusions)

IEM Some associations
INITIAL FINDINGS ( POOR FEEDING , VOMITING , LETHARGY, CONVULSIONS ,COMA )
METABOLIC DISORDER
INFECTION
OBTAIN PL. NH3
HIGH NORMAL
OBTAIN BLOOD Ph & CO2
ACIDOSIS
NORMAL
UREA CYCLE DEFECTS
ORGANIC ACIDEMIAS
AMINOACIDOPATHIES
GALACTOSEMIA

Inborn Errors of Metabolism.ppt

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23 March 2010

Metabolic Disorders - Inborn Errors of Metabolism



Metabolic Disorders - Inborn Errors of Metabolism
By:Dr. Sara Mitchell

Overview
* Proteins - what are they and what do they do?
* Amino Acids - what are they and what do they do?

Eight Essential Amino Acids
* Tryptophan
* Lysine
* Methionine
* Phenylaline
* Theronine
* Valine
* Leucine
* Isolecucine

Inborn Errors of metabolism
* Affects amino acid & protein, carbohydrate, and lipid metabolism.
* Most disorders are autosomal recessive in transmission
* Most disorders are evident at or soon after birth.
* Early detection and treatment are essential to the prevention of irreversible cognitive impairment and early death

Newborn Screening: What is it?
* A test developed in 1961 by Dr. Robert Guthrie to evaluate infants for certain genetic anomalies, inborn errors of metabolism, and other disorders.

http://health.state.ga.us/programs/nsmscd/

Phenylketonuria (PKU):What is it?
* The most common amino acidemia. Classic PKU develops in the absence of the enzyme phenylalanine hydroxylase.
* Incidence

Phenylketonuria: How’s it happen?
* Cause
o absent Phenylalanine hydroxylase causes a build up phenylalanine
* Effect

Phenylketonuria
* Treatment
* Prognosis

Galactocemia: What is it?
* An inborn error of carbohydrate metabolism in which the hepatic enzyme galactose 1-phosphate uridine transferase is absent.
* Incidence

Galactocemia: How does it happen?
Galactocemia: What are the clinical manifestations?
Galactocemia: Diagnosis & Treatment
* Diagnosis
* Treatment

Metabolic Disorders - Inborn Errors of Metabolism.ppt

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Amino Acid Catabolism: Carbon Skeletons



Amino Acid Catabolism: Carbon Skeletons
Copyright © 1999-2007 by Joyce J. Diwan.
All rights reserved.

Molecular Biochemistry II

Amino Acid Carbon Skeletons
Amino acids, when deaminated, yield a-keto acids that, directly or via additional reactions, feed into major metabolic pathways (e.g., Krebs Cycle).
Amino acids are grouped into 2 classes, based on whether or not their carbon skeletons can be converted to glucose:

o glucogenic
o ketogenic.

Carbon skeletons of glucogenic amino acids are degraded to:
o pyruvate, or
o a 4-C or 5-C intermediate of Krebs Cycle. These are precursors for gluconeogenesis.
Glucogenic amino acids are the major carbon source for gluconeogenesis when glucose levels are low.
They can also be catabolized for energy, or converted to glycogen or fatty acids for energy storage.

Carbon skeletons of ketogenic amino acids are degraded to:
o acetyl-CoA, or
o acetoacetate.

Acetyl CoA, & its precursor acetoacetate, cannot yield net production of oxaloacetate, the gluconeogenesis precursor.
For every 2-C acetyl residue entering Krebs Cycle, 2 C leave as CO2.
Carbon skeletons of ketogenic amino acids can be catabolized for energy in Krebs Cycle, or converted to ketone bodies or fatty acids.
They cannot be converted to glucose.
The 3-C a-keto acid pyruvate is produced from alanine, cysteine, glycine, serine, & threonine.
Alanine deamination via Transaminase directly yields pyruvate.
Serine is deaminated to pyruvate via Serine Dehydratase.
Glycine, which is also product of threonine catabolism, is converted to serine by a reaction involving tetrahydrofolate (to be discussed later).

The 4-C Krebs Cycle intermediate oxaloacetate is produced from aspartate & asparagine.
Aspartate transamination yields oxaloacetate.
Aspartate is also converted to fumarate in Urea Cycle. Fumarate is converted to oxaloacetate in Krebs cycle.
Asparagine loses the amino group from its R-group by hydrolysis catalyzed by Asparaginase.
This yields aspartate, which can be converted to oxaloacetate, e.g., by transamination.
The 4-C Krebs Cycle intermediate succinyl-CoA is produced from isoleucine, valine, & methionine.
Propionyl-CoA, an intermediate on these pathways, is also a product of b-oxidation of fatty acids with an odd number of C atoms.
The branched chain amino acids initially share in part a common pathway.
Branched Chain a-Keto Acid Dehydrogenase (BCKDH) is a multi-subunit complex homologous to Pyruvate Dehydrogenase complex.
Genetic deficiency of BCKDH is called Maple Syrup Urine Disease (MSUD).
High concentrations of branched chain keto acids in urine give it a characteristic odor.
Propionyl-CoA is carboxylated to methylmalonyl-CoA.
A racemase yields the L-isomer essential to the subsequent reaction.
Methylmalonyl-CoA Mutase catalyzes a molecular rearrangement: the branched C chain of methylmalonyl-CoA is converted to the linear C chain of succinyl-CoA.
The carboxyl that is in ester linkage to the thiol of coenzyme A is shifted to an adjacent carbon atom, with opposite shift of a hydrogen atom.

Recall that coenzyme A is a large molecule.
Coenzyme B12, a derivative of vitamin B12 (cobalamin), is the prosthetic group of Methylmalonyl-CoA Mutase.
A crystal structure of the enzyme-bound coenzyme B12.
Coenzyme B12 contains a heme-like corrin ring with a cobalt ion coordinated to 4 ring N atoms.
o methyl C atom of 5'-deoxyadenosine (not shown).
o an enzyme histidine N
When B12 is free in solution, a ring N of the dimethylbenzimidazole serves as axial ligand to the cobalt.
When B12 is enzyme-bound, a His side-chain N substitutes for the dimethylbenzimidazole.
Within the active site, the Co atom of coenzyme B12 has 2 axial ligands:
Homolytic cleavage of the deoxyadenosyl C-Co bond during catalysis yields a deoxyadenosyl carbon radical, as Co3+ becomes Co2+.
Reaction of this with methylmalonyl-CoA generates a radical substrate intermediate and 5'-deoxyadenosine.
Following rearrangement of the substrate, the product radical abstracts a H atom from the methyl group of 5'-deoxyadenosine.
This yields succinyl-CoA and the 5'-deoxyadenosyl radical, which reacts with coenzyme B12 to reestablish the deoxyadenosyl C-Co bond.

Methyl group transfers are also carried out by B12 (cobalamin).
Methyl-B12 (methylcobalamin), with a methyl axial ligand substituting for the deoxyadenosyl moiety of coenzyme B12, is an intermediate of such transfers.
E.g., B12 is a prosthetic group of the mammalian enzyme that catalyzes methylation of homocysteine to form methionine (to be discussed later).
o Vitamin B12 is synthesized only by bacteria.
Ruminants get B12 from bacteria in their digestive system.
Humans obtain B12 from meat or dairy products.
o Vitamin B12 bound to the protein gastric intrinsic factor is absorbed by cells in the upper part of the human small intestine via receptor-mediated endocytosis.
B12 synthesized by bacteria in the large intestine is unavailable.
Strict vegetarians eventually become deficient in B12 unless they consume it in pill form.
o Vitamin B12 is transported in the blood bound to the protein transcobalamin, which is recognized by a receptor that mediates uptake into body cells.

Explore via Chime
Methylmalonyl-CoA Mutase
with its prosthetic group,
Coenzyme B12.
Desulfo-CoA (without the
thiol) is at the active site.
The deoxyadenosyl moiety is lacking in the crystal.

The 5-C Krebs Cycle intermediate a-ketoglutarate is produced from arginine, glutamate, glutamine, histidine, & proline.
Glutamate deamination via Transaminase directly yields a-ketoglutarate.
Glutamate deamination by Glutamate Dehydrogenase also directly yields a-ketoglutarate.
Histidine is first converted to glutamate. The last step in this pathway involves the cofactor tetrahydrofolate.
Tetrahydrofolate (THF), which has a pteridine ring, is a reduced form of the B vitamin folate.
Within a cell, THF has an attached chain of several glutamate residues, linked to one another by isopeptide bonds involving the R-group carboxyl.
THF exists in various forms, with single-C units, of varying oxidation state, bonded at N5 or N10, or bridging between them.
In these diagrams N10 with R is r-aminobenzoic acid, linked to a chain of glutamate residues.
The cellular pool of THF includes various forms, produced and utilized in different reactions.
N5-formimino-THF is involved in the pathway for degradation of histidine.
Reactions using THF as donor of a single-C unit include synthesis of thymidylate, methionine, f-methionine-tRNA, etc.
In the pathway of histidine degradation, N-formiminoglutamate is converted to glutamate by transfer of the formimino group to THF, yielding N5-formimino-THF.
Because of the essential roles of THF as acceptor and donor of single carbon units, dietary deficiency of folate, genetic deficiencies in folate metabolism or transport, and the increased catabolism of folate seen in some disease states, result in various metabolic effects leading to increased risk of developmental defects, cardiovascular disease, and cancer.

Aromatic Amino Acids
Aromatic amino acids phenylalanine & tyrosine are catabolized to fumarate and acetoacetate.
Hydroxylation of phenylalanine to form tyrosine involves the reductant tetrahydrobiopterin. Biopterin, like folate, has a pteridine ring.
Dihydrobiopterin is reduced to tetrahydrobiopterin by electron transfer from NADH.
Thus NADH is secondarily the e- donor for conversion of phenylalanine to tyrosine.
Overall the reaction is considered a mixed function oxidation, because one O atom of O2 is reduced to water while the other is incorporated into the amino acid product.
O2, tetrahydrobiopterin, and the iron atom in the ferrous (Fe++) oxidation state participate in the hydroxylation.
O2 is thought to react initially with the tetrahydrobiopterin to form a peroxy intermediate.
Phenylalanine Hydroxylase includes a non-heme iron atom at its active site.
X-ray crystallography has shown the following are ligands to the iron atom:
His N, Glu O & water O.
(Fe shown in spacefill & ligands in ball & stick).
deamination via transaminase) accumulate in blood & urine.
Mental retardation results unless treatment begins immediately after birth. Treatment consists of limiting phenylalanine intake to levels barely adequate to support growth. Tyrosine, an essential nutrient for individuals with phenylketonuria, must be supplied in the diet.
Genetic deficiency of Phenylalanine Hydroxylase leads to the disease phenylketonuria.
Phenylalanine & phenylpyruvate (the product of phenylalanine
Tyrosine is a precursor for synthesis of melanins and of epinephrine and norepinephrine.
High [phenylalanine] inhibits Tyrosine Hydroxylase, on the pathway for synthesis of the pigment melanin from tyrosine. Individuals with phenylketonuria have light skin & hair color.
Methionine S-Adenosylmethionine by ATP-dependent reaction.
SAM is a methyl group donor in synthetic reactions.
The resulting S-adenosylhomocysteine is hydrolyzed to homocysteine.
Homocysteine may be catabolized via a complex pathway to cysteine & succinyl-CoA.
Or methionine may be regenerated from homocysteine by methyl transfer from N5-methyl-tetrahydrofolate, via a methyltransferase enzyme that uses B12 as prosthetic group.
The methyl group is transferred from THF to B12 to homocysteine.
Another pathway converts homocysteine to glutathione.
In various reactions, S-adenosylmethionine (SAM) is a donor of diverse chemical groups including methylene, amino, ribosyl and aminoalkyl groups, and a source of 5'-deoxyadenosyl radicals.
But SAM is best known as a methyl group donor.

Examples:
S-adenosylmethionine as methyl group donor
o methylation of bases in tRNA
o methylation of cytosine residues in DNA
o methylation of norepinephrine epinephrine
o conversion of the glycerophospholipid
phosphatidyl ethanolamine phosphatidylcholine via methyl transfer from SAM.
Enzymes involved in formation and utilization of S-adenosylmethionine are particularly active in liver.
Liver has important roles in synthetic pathways involving methylation reactions, & in regulation of blood methionine.
Methyl Group Donors

Methyl group donors in synthetic reactions include:

* methyl-B12
* S-adenosylmethionine (SAM)
* N5-methyl-tetrahydrofolate (N5-methyl-THF)
Lysine & Tryptophan

Amino Acid Catabolism: Carbon Skeletons.ppt

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Phenylketonuria (PKU)



Phenylketonuria (PKU)
(fen'-il-kee'-to-nu'-ria)
By:Ashley Ryan

What is PKU?

* An inherited metabolic disease in which mental retardation can be prevented by a specific diet
* 1 out of 50 people are carriers of defective gene; 1 in 10,000 births
* Rare condition where a baby is born lacking the ability to break down phenylalanine.
* Phenylalanine is an amino acid found in many foods. It is characterized by higher than normal levels of phenylalanine in the blood which can cause damage to the brain and mental retardation
* The brain suffers and is damaged due to a tremendous buildup of phenylalanine

*This then results in damage of the CNS & causes brain damage

Causes & Symptoms
* Since PKU is inherited it is passed down through families
* Which means both parents must pass on the defective gene to there offspring; known as an autosomal recessive trait
* Phenylalanine is involved in the body’s production of melanin which is the pigment for skin and hair color – children with PKU generally have lighter skin, hair and eyes
* Other symptoms include

Treatment
* PKU is in fact treatable with the correct strictly followed diet very low in phenylalanine
* If diet is not followed brain impairment can occur or error of metabolism can be associated with M.R in first year of life.
* Association with attention-deficit hyperactivity disorder (ADHD) most common problem in those who don’t follow a strict diet
* If diet is properly followed esp. in first few years of life where it is most crucial an outcome of better physical and mental health will follow
* Examples of foods low in phenylalanine: milk, eggs, fish oil, special formula called Lofenalac .
* Lofenalac provides essential amino acids and can be used throughout life. It not only provides amino acids but also vitamins and minerals.
* Can think of it as a super food for PKU patients

Testing for PKU
* It is IMPERTATIVE that phenylalanine restrictions on diet is introduced after birth to prevent the neurodevelopment effects of PKU
* How is PKU tested?
* Blood is routinely drawn from the infants for testing
* A “heel stick” is done and then collected on special blotter paper
* Routine testing includes phenylketonuria and blood type

Prevention
* Overall highly recommend to have strong relationship with physician
* An Enzyme Assay can determine if parents carry defective gene
* Chorionic villus Sampling - screen unborn baby for possibility of PKU
* It is very important that women with PKU closely follow a strict low-phenylalanine diet both before becoming pregnant and throughout the pregnancy, since build-up of this substance will damage the developing baby even if the child has not inherited the defective gene.

Age and Diet- controversy
* The age when a diet can or should be discontinued has been debatable over decades
* Generally- PKU centers advise a life-long diet  especially for female patients
* A study was done that looked at progress of children who ended their diet at an early age
* the main focus of the study was the effects on neurological/ intellectual performance
* The participants abilities were compared during treatment and after the diet was discontinued
* RESULTS- It was shown that children who maintained the diet had fewer deficits to those terminating the diet before the age of 10
* Overall the study said a diet should remain strict to at least the age of 10!
* Although this was said also recommended to maintain diet in adulthood
* can be modified but not completely eliminated

Issues in Adults with PKU
* Several studies said that discontinuation of diet effect
* New problems with PKU:
* Adults w/ PKU who remained on diet but weren't as strict w what they ate showed white matter abnormalities when given MRI indicating a reduction in myelin.
* *** These conditions disappeared after reintroducing the strict diet ***
* Neurological investigations in early treated adults w/ PKU who stopped the diet showed higher incidence of neurological signs including:

-tremors
-clumsy motor coordination
* Investigation on Psychological problems also
-severe behavior/ psychiatric problems are seen in profound retarded/untreated adults w/ PKU in their 30’s-40’s.
* Claims that reintroduction of restricted diet symptoms can sometimes be reversible
* Adults who discontinued the diet have had cases of
* - depression, anxiety, social withdrawal, phobias, low self-esteem, neurotic behavior
* In 2009 it was stated PKU patients should be encouraged to remain on a life long diet and also recommended to:

-take nutritional supplements
* Blood PhE levels should be monitored every 3 months
* Yearly clinical review
* PKU pregnant women recommendations include:
* Being under control of physician specialized in
* metabolic disease, gynecologist, and dietician
* Detailed ultrasound @ 20 weeks of gestation
* Seen every 3 to 4 weeks and blood PhE levels monitored at least 1 a week

Factors to consider when people discontinue restricted diets
* Difficulty maintaining diet for older children
* State support of formula costs is decreasing
* In 1978 85% of PKU programs received financial backing, within 6 years 66% of people received financial support
* Formula Cost can range from $5,000 to $7,000 a year. For a young adult and families can be a problem financially if not receiving any support
* Therefore, when people do stop the restricted diet its important to consider and assess financial, nutritional, social, psychological problems that people encounter trying to maintain the diet. And remember that in some cases people don’t discontinue the diet because they want to they may be unable to.

Reference Page
Phenylketonuria (PKU)

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Case Study: Phenylketonuria (PKU)



Case Study: Phenylketonuria (PKU)
By: Bobby Orr
Adam Edwards
Danielle Heinbaugh

Introduction: What is PKU?
* PKU (Phenylketonuria) is a disorder defined as the inability to metabolize the essential amino acid phenylalanine
* This can cause mental retardation, if untreated, although sufficient treatment can occur immediately after birth

Symptoms:
* The main symptom consists of mild to moderate mental retardation, but this is easily prevented through treatment
* However, other side effects include seizures, vomiting, a “mousy odor”, and behavioral self-mutilation
* In some cases, treatment can reduce or reverse the mental retartadtion

The Guthrie Test:
* determines the phenylalanine level in the blood
* should be done on the second or third day of life
* is a screening test done to identify elevated phenylalanine levels it is not diagnostic
* PKU babies’ phenylalanine level is usually 20-40 mg/dl in comparison with normal levels of 4-6 mg/dl.

How the Guthrie Test works:
* Blood on filter paper is placed on agar plates with a strain of bacillus subtilis that requires phenylalanine for growth.
* The presence of growth is indicated by a halo surrounding the filter paper.
* If positive, blood phenylalanine and tyrosine levels are determined, and if elevated, a confirmatory assay for phenylalanine hydroxylase is done.

PKU Inheritance:
* Inherited as autosomal recessive disorder.
* Variation to classical symptoms is result of compound heterogeneity.
* 65 allelic variants make compound heterogeneity more common then homogeneity for the same allele.

Treatment of PKU:
* Phenylketonuria is treatable with a low phenylalanine diet.
* phenylalanine levels should be kept below 15 mg per deciliter
* Nutra sweet is especially high in phenylalanines

Genetic Counseling:
* Tell the parents that the baby will be normal if they follow the prescribed dietary guidelines
* The child is normally out of danger of the disease after puberty
* Phenylalanine should be avoided
o Stay away from nutra sweet, meats, dairy products

Case Study: Phenylketonuria (PKU)

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27 September 2009

Smith-Lemli-Opitz Syndrome



Smith-Lemli-Opitz Syndrome (SLOS)
By: Suraj Gathani

Description and Occurrence
* Autosomal recessive disorder
o Cholesterol metabolism effected.
* Common characteristics:
o Multiple malformations at birth.
o Mental retardation later.
* Occurrence:
o 1 in 20,000 people of central European decedents.
o Rare in Africans and Asians.

Clinical Features
* Clinical anomalies:
o Mental retardation (100% affected)
o Small brain at birth (microcephaly) >90%
o Second and third toe fusion (synadactyly) ~98%
o Genital abnormalities in males >50%
o Muscle weakness (hypotonia) ~50%
o Polydactyly
o Abnormalities of heart, lung, kidneys, and liver.

Smith-Lemli-Opitz Syndrome
* Distinctive facial features:
o High, broad forehead
o Narrow temples
o Upward pointing nostrils
o Drooping eyelids and a broad nasal bridge
* Behavioral characteristics:
o Repeated self injury
o Prolonged temper tantrums & violent outbursts
o Hyperactivity

Molecular Defects
* Caused from mutation in the DHCR7 gene
o Located at 11q12-13
o Encodes for sterol-Δ7-reductase
* Defects in sterol-Δ7-reductase
o Build up of 7-dehydrocholesterol
o Deficiency of cholesterol
* Importance of cholesterol
o Important component in cell membrane and myelin sheaths
o Precursor for steroid hormones such as progesterone
o Precursor for bile salts

Cholesterol Metabolism
Diagnosis and Treatment
* Diagnosis:
o Detection of an elevated level of 7-dehydrocholesterol in plasma
* Treatment:
o Individuals with SLOS need support and care
o Congenital abnormalities can be corrected with surgery.
o Dietary cholesterol supplementation is beneficial.

Reference

Smith-Lemli-Opitz Syndrome.ppt

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25 May 2009

Inborn Errors of Metabolism



Inborn Errors of Metabolism
By:Robert D. Steiner, MD
Associate Professor, Pediatrics and Molecular and Medical Genetics
Head: Division of Metabolism, OHSU

Inborn Errors of Metabolism
* IEM as a group are not rare: occur 1 in 5000 births collectively
* Often treatable if diagnosed
* Most difficult task for clinician is to know when to consider IEM and which tests to order for evaluation
* Don’t be fooled--other diagnoses like sepsis, ICH, pulm. hem. may accompany IEM
* Clues to presence of IEM may often be found in FH

Metabolic Diseases Which Can Present in Crisis
“Stumbling Blocks” in Diagnosing Inborn Errors of Metabolism
* Signs and symptoms are often nonspecific
o Routine childhood illnesses excluded 1st
o Inborn errors considered only secondarily
* Unfamiliarity with biochemical interrelationships/ diagnostic tests
o Inappropriate sample collection
o Inappropriate sample storage
* Every child with unexplained . . .
o Neurological deterioration
o Metabolic acidosis
o Hypoglycemia
o Inappropriate ketosis
o Hypotonia
o Cardiomyopathy
o Hepatocellular dysfunction
o Failure to thrive

. . . should be suspected of having a metabolic disorder

When to suspect an IEM
EFFECT ON OTHER METABOLIC ACTIVITY
e.g., activation, inhibition, competition
Theoretical consequences of an enzyme deficiency.
First Steps in Metabolic Therapy for Inborn Errors of Metabolism
* Reduce precursor substrate load
* Provide caloric support
* Provide fluid support
* Remove metabolites via dialysis
* Divert metabolites
* Supplement with cofactor(s)

Therapeutic Measures for IEM
* D/C oral intake temporarily
* Usually IVF’s with glucose to give 12-15 mg/kg/min glu and at least 60 kcal/kg to prevent catabolism (may worsen PDH)
* Bicarb/citrate Carnitine/glycine
* Na benzoate/arginine/citrulline
* Dialysis--not exchange transfusion
* Vitamins--often given in cocktails after labs drawn before dx is known

Treatment of the Acutely Sick Child
General Therapy
* Maintain vital functions
o Oxygenation
o Hydration
o Acid/Base balance

Specific Therapy
* Treat infection
* High dose I.V. glucose
* Carnitine supplementation

STRIVE TO IDENTIFY PRIMARY METABOLIC DISORDER
TREATMENT OF GENETIC DISEASES
* MODIFY ENVIRONMENT, e.g., diet, drugs
* SURGICAL, correct or repair defect or organ transplantation
* MODIFY OR REPLACE DEFECTIVE GENE PRODUCT, megadose vitamin therapy or enzyme replacement
* REPLACE DEFECTIVE GENE
* CORRECT ALTERED DNA IN DEFECTIVE GENE

Newborn Screening
* PKU - must do on all infants in NICU even if not advanced to full feeds
o Positive--transient HPA, tyr, liver disease, benign HPA, classical PKU
* Galactosemia-
* Hypothyroidism
* Hemoglobinopathies
* Biotinidase def, CAH (21-OH’ase def),
* MSUD

Metabolic Disorders Presenting as Severe Neonatal Disease
What to do for the Dying Infant Suspected of Having an IEM

Inborn Errors of Metabolism.ppt

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CALCIUM METABOLISM



CALCIUM METABOLISM

CALCIUM METABOLISM
* PHYSIOLOGY OF CALCIUM METABOLISM
* HYPERCALCEMIA
* HYPOCALCEMIA
* METABOLIC BONE DISEASES

CALCIUM PHYSIOLOGY: BLOOD CALCIUM

* BLOOD CALCIUM IS TIGHTLY REGULATED
o PRINCIPLE ORGAN SYSTEMS
o HORMONES
o INTEGRATED PHYSIOLOGY OF ORGAN SYSTEMS AND HORMONES MAINTAIN BLOOD CALCIUM

CALCIUM PHYSIOLOGY: BLOOD CALCIUM

* CALCIUM FLUX INTO AND OUT OF BLOOD
CALCIUM HOMEOSTASIS
DIETARY CALCIUM
INTESTINAL ABSORPTION
ORGAN PHYSIOLOGY
ENDOCRINE PHYSIOLOGY
DIETARY HABITS,
SUPPLEMENTS
BLOOD CALCIUM
BONE
KIDNEYS
URINE


VITAMIN D PHYSIOLOGY
VITAMIN D SYNTHESIS
TISSUE-SPECIFIC VITAMIN D RESPONSES
VITAMIN D MECHANISM OF ACTION: VITAMIN D RECEPTOR
VITAMIN D REPCEPTOR: TRANSCRIPTIONAL REGULATION
VITAMIN D MECHANISM OF ACTION
VITAMIN D RESPONSIVE GENE
TRANSCRIPTION START SITE
FUNCTION OF VITAMIN D
PARATHYROID HORMONE (PTH) PHYSIOLOGY
CALCIUM, PTH, AND VITAMIN D FEEDBACK LOOPS
CALCIUM FEEDBACK TO REGULATE PTH SECRETION
CALCIUM SENSING RECEPTOR: CLINICOPATHOLOGIC CORRELATES
PTH RECEPTOR CLINICOPATHOLOGIC CORRELATES
ORGAN PHYSIOLOGY AND CALCIUM METABOLISM
GI PHYSIOLOGY
RENAL PHYSIOLOGY
BONE PHYSIOLOGY
MEASUREMENT OF BONE TURNOVER
HYPERCALCEMIA: SIGNS AND SYMPTOMS
CAUSES OF HYPERCALCEMIA
PRIMARY HYPERPARATHYROIDISM
TREATMENT OF PRIMARY HYPERPARATHYROIDISM
HYPERVITAMINOSIS D
HYPERVITAMINOSIS D: CLINICAL CHARACTERISTICS
NON-HORMONAL HYPERCALCEMIA
RENAL FAILURE-ASSOCIATED HYPERCALCEMIA
DRUG-INDUCED HYPERCALCEMIA
HYPOCALCEMIA: SIGNS AND SYMPTOMS
CAUSES OF HYPOCALCEMIA
HYPOCALCEMIA: HYPOPARATHYROIDISM
HYPOPARATHYROIDISM: TREATMENT
HYPOPARATHYROIDISM: TREATMENT SUMMARY
HYPOCALCEMIA: HYPOVITAMINOSIS D
DEFECTIVE VITAMIN D FUNCTION
NON-PARATHYROID HYPOCALCEMIA: SECONDARY HYPERPARATHYROIDISM
HYPERPARATHYROIDISM: PRIMARY vs. SECONDARY
SECONDARY HYPERPARATHYROIDISM
RICKETS AND OSTEOMALACIA
RICKETS AND OSTEOMALACIA: CLINICAL MANIFESTATIONS
RICKETS AND OSTEOMALACIA: CAUSES

CALCIUM METABOLISM.ppt

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Disorders of Sodium and Potassium Metabolism



Disorders of Sodium and Potassium Metabolism

Outline
* Review of sodium and potassium metabolism
* Paradigm for analyzing pathophysiology
* Abnormalities of potassium balance
* Abnormalities of sodium and water balance
* Example cases

Major Mediators of Sodium and Water Balance
* Angiotensin II
* Aldosterone
* Antidiuretic hormone (ADH)

Renin-Angiotensin-Aldosterone Axis

Angiotensin II
Aldosterone
Role of ADH (antidiuretic hormone)
Overview of Biochemical Homeostasis
Overview of Potassium Balance
Etiologies of Hyperkalemia
Excessive Dietary Intake
Decreased Urinary Excretion
Internal Redistribution
Etiologies of Hypokalemia
Poor Intake
Increased Urinary Excretion
Increased GI Losses
Diarrhea
Laxative abuse
Vomiting / NG drainage

Increased Transcutaneous Losses
Transmembrane Shift
Overview of Sodium Balance
Etiologies of Hyponatremia
Poor Intake of Sodium
Increased Urinary Loss of Sodium
Increased GI Loss of Sodium (Fluid loss must be followed by repletion with free water).
Increased Transcutaneous Loss of Sodium (Fluid loss must be followed by repletion with free water).
Excessive Intake of Water (1° polydipsia)
Decreased Urinary Excretion of Water
Transmembrane Shift of Water
Primary Sodium Loss
Primary Water Excess
Etiologies of Hypernatremia
Primary Sodium Excess
Excess Intake of Sodium
Decreased Urinary Excretion of Sodium
Primary Water Loss
Poor Intake of Water
Increased Urinary Loss of Water
Increased GI Loss of Water
Increased Transcutaneous Loss of Water
Transmembrane Shift of Water (most often due to rapid production of intracellular lactate)

4 Case studies

Disorders of Sodium and Potassium Metabolism.ppt

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