Disorders Of Monosaccharide Metabolism

Question 1

Pyruvate kinase deficiency

Answer 1

. Most common glycolytic enzyme w/ deficiency
. Hemolytic anemia and jaundice
. Autosomal recessive gene
. Mechanism: lack of anaerobic glycolysis in. erythrocytes causes lack of ATP impairing Na-K ATPase maintaining plasma membrane
. Treatment: blood transfusions, sometimes spleen removal

Question 2

Glucokinase deficiency

Answer 2

. Complete deficiency causes intrauterine growth retardation and insulin-treated DM from birth
. Autosomal recessive, heterozygous carriers w/ some enzyme activity develop form of DM that requires insulin treatment later in life (Maturity onset diabetes of the young)
. Mechanism: pancreatic beta cells can’t release insulin appropriately and blood glucose isn’t regulated
. Heterozygous patients lack symptoms but have hyperglycemia when tested

Question 3

Disaccharidases

Answer 3

. Digestive enzymes hydrolytically cleave disaccharides into monosaccharides
. Attached to luminal surface of brush border membrane of small intestine

Question 4

Trehalase deficiency

Answer 4

. Cleaves trehalose (disaccharide of glucose high in mushroom)
. People have poop shoots/gas up in consumption of trehalose
. Treatment: avoid mushrooms and foods w/ trehalose

Question 5

Lactase deficiency w/ age

Answer 5

. Common
. Lactase expression in infants high then decreases w/ weaning
. People lose 90% or more of lactase by adulthood (esp African or Asian decent)
. SymptomsL poop shoots, gas, bloating, and. Abdominal discomfort

Question 6

Celiac disease

Answer 6

. Autoimmune disease where antibodies to gluten damage GI villi when gluten is consumed
. Avoidance of gluten required
. Symptoms: digestive difficulties and failure to thrive in children

Question 7

Average percentage of fructose in American diet

Answer 7

. 10%

Question 8

Primary site of metabolism of dietary fructose and pathway

Answer 8

. Liver

. Pathway: fructokinase (adds P to fructose) and Aldolase B (cleaves product into glycolytic intermediates)

Question 9

Fructokinase deficiency (essential fructosuria)

Answer 9

. Autosomal recessive
. Symptoms: people lacking enzyme simple excrete fructose in urine
. Mechanism: fructose accumulates in blood and is excreted into urine, some taken up in tissues
. Treatment: none, harmless condition

Question 10

Aldolase B deficiency (hereditary fructose intolerance)

Answer 10

. Autosomal recessive
. Severe hypoglycemia, vomiting, jaundice, hyperuricemia, hemorrhage, lactic academia, hepatomegaly, lead to liver failure/death
. Mechanism: accumulated of phosphorylated fructose in liver cells result in inhibition of other pathways causing liver damage
. Treatment: removes sources fo fructose from diet

Question 11

Galactose metabolism

Answer 11

. Doesn’t need insulin
. Liver site for metabolism
. Galactose is phosphorylated then attached to UDP and altered

Question 12

Galactokinase deficiency

Answer 12

. Autosomal recessive
. Galactosemia and galactosuria, cataracts
. Mechanism: consumption of galactose in patients causes high levels in blood so galactose accumulates in cells including those containing aldose reductase that converts galactose to galactitol
. Causes osmotic problems leading to cataracts
. Treatment: eliminate dietary galactose

Question 13

Galactose 1-phosphate uridyltransferase deficiency (classic galactosemia)

Answer 13

. Autosomal recessive
. Causes galactosemia, galacosuria, vomiting, diarrhea, jaundice, liver damage, mental impairment, cataracts
. Mechanism: accumulation of phosphorylated galactose and galactitol in tissues that inhibits pathways causing damage
. Treatment: eliminate galactose

Question 14

Why do cataracts occur in patients w/ galactose enzyme deficiencies

Answer 14

. Aldose reductase that acts on galactose to hydrolyze it is expressed in retina and lens
. Accumulation of sugar alcohols causes cataracts

Question 15

Common features of glycogen storage diseases

Answer 15

. Autosomal recessive
. Enlarged organs from accumulated glycogen that can’t be used
. Symptoms assoc. w/ tissue that is affected

Question 16

Von Gierke Disease

Answer 16

. Most common glycogen storage disease
. Deficient in glucose 6-phosphatase
. Patients high high level glycogen in liver and kidney
. Symptoms: patients prone to severe fasting hypoglycemia and ketosis, lactic acidemia, hyperlipidemia, hyperuricemia
. Mechanism: glucose-6-phosphatase needed for glucose transporter will not bind to phosphorylated glucose
. Treatment: nocturnal infusions of glucose

Question 17

McArdle Syndrome

Answer 17

. Deficient in skeletal muscle glycogen phosphorylase
. Patients possess high levels of glycogen in muscle
. Symptoms: during exercise patients will experience weakness and cramping, myoglobinemia and myoglobinuria are common, lactate does not go up in strenuous exercise
. Mechanism: lack of glycogen breakdown inhibits anaerobic glycolysis during exertion, releases myoglobin into blood
. Treatment: avoid excessive/ intense exercise

Question 18

Pompe disease

Answer 18

. Deficient in lysosomal alpha (1-4) glucosidase deficiency
. General deficiency buy key organs are heart and skeletal muscle
. Patients have high levels glycogen (normal structure) in abnormal vacuoles in lysosomes
. Symptoms: severe cardiomegaly but normal glucose levels, infantile form causes early death from heart failure
. Mechanism: cardiac
. Treatment: enzyme replacement therapy

Question 19

Cori disease

Answer 19

. Deficient in hepatic de-branching enzyme
. High levels abnormal glycogen ( 1 or 4 glucose residues at branch points) in liver
. Symptoms: fasting hypoglycemia, hyperlipidemia, elevated liver enzymes, hepatomegaly
. Treatment: dietary management, high protein diet

Question 20

Lactic acidemia signs and symptoms

Answer 20

. Nausea, vomiting, abdominal pain, shortness of breath, rapid breathing, tingling sensations on skin
. Lab values: inc. lactic acid in serum, dec. pH

Question 21

Who is at risk for developing high lactic acid

Answer 21

. Patients w. HIV/AIDS taking HAART

. Patients taking multiple drugs for health issues (metformin for DM 2)

Question 22

ABO hemolytic disease

Answer 22

. Mother type O and develops antibodies against non-O

. Antibodies cross placenta and attack baby’s rbcs causing hemolysis