heritable enzyme deficiencies of the carbohydrate metabolism Flashcards
how is the heritable enzyme deficiency usually inherited?
it is usually autosomal resessive and related to the X chromosome
usually homozygous recessive
passed on by heterogenous carriers
diagnosis of heritable enzyme deficiencies?
- diagnosis of certain reaction specific metabolites in the blood and urine
- measurement of enzyme activity (ELISA etc.)
- DNA testing - special test kits are available for frequent diseases
therapy for heritable enzyme deficiencies?
- no specific casual therapy for most of the diseases - only symptomatic therapy
- searching for carriers and excluding from breeding is the real solution
- Genetic therapy -
- Bone marrow transplantation - highly unsuccesful
- Enzyme replacement -systematic replacement of enzymes
Biochemical role of pyruvate kinase?
- one of the enzymes of glycolysis
the 4 subunits of isoenzymes?
- PK - M1 - striated and heart muscle
- PK - M2 - mostly Fetal tissues
- PK - L - Liver
- PK - R - RBCs
what happens if the genes of L and R isoenzymes are damaged?
metabolic disorder in the liver and RBCs
most common breeds to have a lack of pyruvate kinase enzyme?
Dogs:
- Westie
- Beagle
- Chiuahua
Cats:
- Abessinian
- Somali
consequences of lack of PK in the liver?
- Glycogen accumulation
- Hepatomegaly
- Decreased ATP production
- intensive B oxidation
consequences of lack of PK in RBCs?
- Lack of ATP - cell heavily damaged
- membrane not protected from free radicals - membrane is fragile - haemolysis - haemolytic anaemia
- irregular shaped cells - Burr cells
what can cause the formation of Burr cells?
lack of PK
symptoms for the lack of PK?
- Haemolytic anaemia
- Pale mucosal membranes
- Jaundice
therapy for PK deficiency?
- Symptomatic therapy - Splenectomy, transfucion etc.
- not always unfavorable prognosis - patients can live for years with proper treatment
what is Gierke - disease?
lacking the enzyme: glucose - 6 - phosphatase
(liver and kidneys)
consequences of the lack of glucose -6- phosphatase?
- accumulation of glucose -6- phosphate = allosteric activation of glycogen synthase = glycogen accumulation
- Inhibition of blood glucose production - Hypoglycaemia
symptoms of Gierke - disease?
- notably enlarged liver
- skeletal and heart muscle: degeration due to glycogen storage
- strong hypoglycaemic spasms in the case of starvation or intensive load
Gierke - disease therapy?
- symptomatic treatment
- Glucose I.V.
- Special diet - energy deficiency
- unfavourable prognosis in each
what is Pompe - disease?
lacking of enzyme
Lysosomal exo - amylo - 1.4 - glucosidase
glycogen accumulation and energy deficiency = muscle weaknes
symptoms of Pompe - disease?
- cardiomegaly form - large amount of glycogen accumulated in the heart muscle = fast death
- Neuromuscular form: glycogen accumulation in the brain - CNS symptoms
treatment for pompe - disease?
no known treatment
poor prognosis
what is Cori - forbes disease?
lacking of enzyme
amylo - 1.6 - glucosidase (debranching enzyme)
splitting the branches of glycogen during glycogenolysis
Cori forbes disease occurence?
- in akita and german shepherd breeds
pathogenesis and symptoms of cori - forbes disease?
- Muscle disease - weakness - 2 month old dog
- Hepatomegaly
- Hypoglycaemia - in case of starvation
- life span is not reduced significantly
types of cori forbes disease?
- Type I: enzyme deficiency in the liver and the muscles as well
- Type II: enzyme deficiency only in the liver
cori - forbes therapy?
symptomatic therapy - Glucose IV., hepatic protection
Prognosis: not definatley unfavourable
