Enzyme Deficiencies Flashcards
What is the enzyme deficiency in PKU?
Phenylalanine hydroxylase (PAH)
What happens when someone has a PAH deficiency?
PKU:
Phenylalanine cannot be converted to tyrosine
Subsequent buildup of phenylalanine, which is converted to phenylpyruvic acid
PP Acid excreted in urine
People with PKU tend to also have a deficiency in ______, which is required to synthesize ______.
Tyrosine; melanin
What enzyme is deficient in Maple Syrup Urine disease?
Branched-chain ketoacid decarboxylase
What are the branched chain amino acids?
Valine
Isoleucine
Leucine
What happens to to those with branched chain amino acid metabolism disorders?
Valine, leucine, and isoleucine and unable to be carboxylated and subsequently utilized for gluconeogenesis, FA synthesis, and protein synthesis. This leads to them being excreted in urine.
What is the treatment for Maple Syrup Urine disease?
Dietary restriction of intake of the branched chain AAs
What is the single most common genetic condition?
G6P dehydrogenase deficiency
Which pathway is G6PD involved in?
The oxidative step of PPP – cannot convert G-6-P to ribose
What is the net result of G6PDD?
Reduced ability to produce NADPH
Which cells are particularly affected by G6PDD?
Red blood cells – cannot protect themselves from oxidative damage without NADPH (reducing agent)
Symptoms of G6PDD typically do not present until there is an oxidative assault. Three main sources for this are….
- Infection (cold, flu, etc)
- Drugs (NSAIDs, sulfa drugs, quinolones, etc)
- Foods (fava beans, legumes, menthol-containing foods)
Acute oxidative damage in someone with G6PDD can lead to ______.
Hemolytic anemia
What is the clinical presentation of hemolytic anemia?
Paleness Jaundice Dark urine Fatigue SOB Splenomegaly
G6PDD is a significant cause of _____ in newborns.
Jaundice
Why does hemolytic anemia cause jaundice?
Lysis of RBCs releases heme, which is typically broken down to bilirubin and excreted by the liver. An excess of RBCs overloads the liver.
What enzyme is deficient in classical galactosemia?
Galactose 1-phosphate uridyl transferase
What enzyme is deficient in classical galactosemia?
Galactokinase
When does galactosemia present and what does it look like?
First two weeks of life
Newborns present with vomiting, lethargy, failure to thrive, and jaundice
How is galactosemia treated?
Feeding infants formula lacking milk sugars (lactose and galactose)
What enzyme is deficient in fructose intolerance?
Fructose 1-phosphate aldolase (or Aldolase B)
What are the glycogen storage disorders affecting the liver?
Von Gierke disease
Cori disease
Anderson disease
Hepatic phosphorylase deficiency
Enzyme deficiency in Von Gierke disease
Glucose-6-phosphatase
Enzyme deficiency in Cori disease
Amylo-1, 6-glucosidase (debrancher enzyme)
Enzyme deficiency in Anderson disease
Glycogen brancher enzyme
Which glycogen storage disease is involved with glycogenesis?
Anderson disease
Clinical presentation of Von Gierke disease
Hepatomegaly
Hypoglycemia
Clinical presentation of Cori disease
Hepatomegaly
Muscle weakness
Clinical presentation of Anderson disease
Hypotonia
Abnormal liver function within first year of life
Progresses to liver failure very quickly
Clinical presentation of hepatic phosphorylase deficiency
Hepatomegaly
Hypoglycemia
Failure to thrive
Which glycogen storage diseases affect muscle?
Pompe disease
McArdle disease
Enzyme deficiency in Pompe disease
lysosomal enzyme alpha-1,4-glucosidase
necessary for glycogenolysis
Enzyme deficiency in McArdle disease
Muscle phosphorylase (necessary for breakdown of muscle glycogen during exercise)
Enzyme deficiency in CAH
90% of cases are due to 21-hydroxylase
Androgen Insensitivity Syndrome is caused by
Defective testosterone receptors
What is the most common autosomal dominant single-gene disorder in Western society?
Familial hypercholesterolemia
Familial hypercholesterolemia leads to
Premature coronary artery disease
What is the treatment for familial hypercholesterolemia?
Dietary restrictions and use of statins (HMG-CoA reductase inhibitors)
Pathology of familial hypercholesterolemia
Problems with LDL receptor:
- Reduced/defective biosynthesis
- Reduced/defective transport
- Abnormal binding of LDL by the receptor
- Abnormal internalization of the receptor
Problems with LDL receptors leads to…
Increased endogenous synthesis of cholesterol
Two examples of mucopolysaccharidoses
Hunter syndrome
Sanfilippo (most common)
Calling card of MPSs
Coarsening of facial features
babies look like grown men
Tay Sachs death usually occurs because of
Respiratory infections
Enzyme deficiency in Tay Sachs
Subunit of beta-hexosaminidase
Calling card of Tay Sachs
Cherry red spot in center of macula fundus
Most common sphingolipidoses
Gaucher
Enzyme deficiency in Gaucher
Glucosylceramide beta-glucosidase
Enzyme deficiency in Lesch Nyhan
HGPRT
What is HGPRT involved in?
Salvage pathway of purine synthesis
Lesch Nyhan patients produce more/less purines
More
200x higher levels
Results in excess uric acid
How is Lesch Nyhan treated?
Allopurinol
What does adenosime deaminase do in the body?
Responsible for conversion of AMP to IMP in the purine salvage pathway
Why is SCID known as “bubble boy” syndrome?
Patients with ADA are severely deficient in both T and B cells, leaving them without a functional immune system
Adenosine deaminase deficiency is responsible for approx. 15% of cases of….
Severe combined immunodeficiency syndrome (SCID)
Potential future treatment for SCID
Gene therapy: inserting function adenosine deaminase gene using retroviral vectors
Potential complication of using gene therapy for SCID
Patients in clinical trial developed leukemia
What are porphyrins?
Ringed structures which can chelate metal ions
Two main tissues affected by porphyrin metabolism disorders…
Liver – cytochromes
Erythrocytes – hemoglobin
Enzyme deficiency in acute intermittent porphyria
Uroporphyrinogen I synthase
