Bio 32 Metabolic Diseases Flashcards
Why are enzymopathies usually autosomal recessive disorders?
Most proteins are produced at levels well in excess of what is really needed to function normally. So even if a person is heterozygous and produces 1/2 the normal amount, chances are they will still be normal.
Recessive traits usually involve_________?
enzymes or peptide hormones
Dominant traits usually involve__________?
non-enzymatic or structural proteins
What usually causes the problem when there is a disfunction with an enzyme?
Excess of substrate or lack of product
Explain difference between diffusible and macromolecular substrates and their effects.
Small molecule disorders involve molecules that are small and found throughout the body and can easily move throughout the body so when something goes wrong, the effects are widespread.
Macromolecular diseases are usually confined to the tissue with the substrate.
Explain what happens with Hereditary Fructose Intolerance (fructose poisoning).
Deficiency in aldolase B causes buildup of Fructose 1-P which causes liver damage because it is osmotically active. It also ties up all the inorganic phosphate in the liver which causes decreased glycogenolysis and decreased ATP synthesis.
Causes severe hypoglycemia because Pi is substrate for glycogen phosphorylase, and can’t do gluconeogenesis because of low ATP.
Jaundice and hepatic failure. Does not cause cataracts.
Treatment is to avoid fructose and sucrose intake.
Explain galactosemia.
Mutations in hepatic galactose 1-P uridyltransferase.
Accumulation of galactose and G1-P. Osmotically active so causes liver damage. High levels lead to production of galactitol from aldose reductase which causes cataracts. Galactitol also damages kidneys and nerves and causes mental retardation.
This is checked for in every baby in all 50 states.
Treatment is avoiding lactose and galactose.
Explain PKU.
PKU is phenylketonuria
Normally, phenylalanine hydroxylase (PAH) converts phenylalanine to tyrosine in the liver. When PAH is deficient, phenylalanine builds up and tyrosine levels drop. Phenylalanine undergoes a side reaction to produce phenylpyruvic acid. Damages CNS and causes mental retardation.
All babies tested with the Guthrie test using a heel prick to test blood for phenylalanine levels.
What is maternal PKU?
People with PKU will sometimes stop limiting their intake of phenylalanine when they are older and have no ill effects. Mothers with the condition will have high levels of phenylalanine and even if the baby has the PAH enzyme, the high levels of phenylalanine will cause mental retardation in the child.
What is type 0 GSD?
GSD=glycogen storage disease
Type 0 is a deficiency in glycogen synthase so glycogen cannot be produced.
Causes fasting hypoglycemia, and hyperglycemia after eating as well as hyperlacticacidemia.
What is type IV GSD?
Deficiency in hepatic branching enzyme for glycogen synthesis. Also called Andersen Disease.
Causes too long of glycogen branches and an immune response and death by 5.
What is type VI GSD?
Partial deficiency in hepatic glycogen phosphorylase so liver swells from glycogen accumulation. Can cause hypoglycemia or no symptoms at all.
What is type V GSD?
McArdle disease.
Deficiency in muscle glycogen phosphorylase.
Exercise induced cramps and intolerance
What is type III GSD?
Cori Disease
Disorder in debranching enzyme
Results in hepatomegaly, hypoglycemia, and myopathy
What is Type I GSD?
von Gierke Disease
Deficiency in glucose 6-Phosphate
Lethargy, seizures, hepatomegaly
