Week 5: Storage diseases Flashcards
What is a storage disease?
products taken up by cells but aren’t processed properly and can get an accumulation of molecules that are abnormal
Types of glycogen storage diseases?
- Hepatic type
- Myopathic type
Describe Myopathic type Glycogen storage disease
Defect in glycogen phosphorylase
Lose capacity for short-term energy needs
Causes low energy, myalgia
Clinically mild
Can still perform β-oxidation so treated with fat intake
Describe Heptaic Type Glycogen Storage Disease
- Issue with glycogen phosphorylase
- Hepatomegaly
- tough to maintain blood glucose so hypoglycemic
- The severe form of glycogen storage disease
- Can still perform gluconeogenesis but it can’t keep up with the lack of glycogenolysis
- Uses Ketones to pick up the slack
What is the severe form of glycogen storage disease
Hepatic type glycogen storage disease
What is the mild form of glycogen storage disease
Myopathic type glycogen storage disease
Specific types of glycogen storage diseases and specific enzymes to Disease
Groups of glycogen storage diseases
Acid maltase???
α-glucosidase (lysosomal deficiency
is an alternative path to generate glucose from glycogen
normally, glycogen is cleaved in the cytoplasm; however, some cytoplasmic glycogen can enter a lysosomal compartment
There is no glycogen phosphorylase in a lysosome so acid maltase is used because of the low pH
This deficiency leads to Pompei Disease
Pompe’s Disease
Hers Disease
McArdle’s Disease
Cori’s Disease
Von Gierke’s Disease
Describe the overall function of the lysosome
Have endocytosis of things such as bacteria
The lysosomes main job is break things and organisms down
Everything that enters a lysosome need to be broken down to their monomers by acid hydrolases
Describe Lysosomal Acidification
PRotein on surface of lysosome that starts out on an endosome called a VATPase which makes the lysosome acidic
VATPase AKA
Vacuolar ATPase
VATPase function
Basically a vacuolar ATPase which is involved in controlling pH of lysosomes by pumping protons against a gradient into the lysosome using ATP
Why does the pH need to be so low in lysosomes?
Because these are dangerous enzymes, the pancreas protects because they need cofactors or need enterokinase activation in the intestine
but in lysosomes, they are not zymogens but instead, they need a lower pH to be active
List of acid hydrolases in lysosomes
- Proteases
- Lipases
- Glycosidases
- DNAses
- RNAses
Pathology of acid hydrolases
theses enzymes are made via transcription and constructed in the ER
Describe The constitutive pathway
Constitutive pathway AKA
Secretory pathway
Describe lysosome synthesis
- lysosome proteins are transcribed and the translated and translocated to the Rough ER and secrete the protein as it is translated into the ER
- then to Golgi, then usually to the plasma membrane, but for a lysosome, all the lysosomal proteins are tagged with mannose-6-phosphate which has a receptor and the mannose-6-phosphate tag gets budded off as the protein enters the lysosome
- Then the VATPase pumps protons in to lower the pH
- Now the hydrolases that are bound to the receptor dissociates from the receptor which is recycled to the Golgi and the hydrolases become activated
Mucolipidosis description
class of lysosomal storage disease
Mucolipidosis types
I-Cell Disease (Inclusion Cell)
Describe I-Cell Disease
There are no mannose-6-phosphate tags so the hydrolases cannot get into the lysosome except by diffusion but not enough get in so most are sent by the constitutive pathway to the plasma membrane and excreted to the Extracellular space
So you will have inclusion bodies in the lysosomes that are composed of components that have not been degraded, primarily are lipids
I-Cell Disease prognosis
death in infancy
Describe Niemann-Pick Disease
- Lipidosis lysosomal storage disease
- NPC1 is deficient so cannot process sphingolipids (primarily sphingomyelin) or no sphingomyelinase
- So you get a buildup of sphingolipids
Fabry’s disease
Lipidosis lysosomal storage disease lacking α-Galactosidase so gangliosides build-up (primarily Gal-gal-glucosylceramide)
Gaucher’s Disease
Lipidosis lysosomal storage disease
β-Glucosidase enzyme missing (mannose-6-phosphate tag deficiency is only in I cell disease)
abnormal accumulation of Cerebrosides (primarily Glucosylceramide)
Tay-Sachs Disease
- Lipidosis Lysosomal Storage Disease
- Deficient in Hexosaminidase A
- Build up of gangliosides (primarily GM2 ganglioside)
What are lipidoses?
Lysosomal storage diseases with the deficiency of an enzyme that degrades a type of glycolipids
What is Mucopolysaccharidosis
Defects in glycosaminoglycans/proteoglycan degradation
Common types of Mucopolysaccharidosis
- Hurler syndrome
- Hunter syndrome
Describe Hurler Syndrome
Deficiencies of the enzymes will lead to accumulation of these structures in the lysosome
Describe Hunter Syndrome
Therapeutic options for storage diseases
Learn all of these diseases and the enzymes and the symptoms and what happens etc, myb first aid
