Week 5: Storage diseases

Question 1

What is a storage disease?

Answer 1

products taken up by cells but aren’t processed properly and can get an accumulation of molecules that are abnormal

Question 2

Types of glycogen storage diseases?

Answer 2

• Hepatic type
• Myopathic type

Question 3

Describe Myopathic type Glycogen storage disease

Answer 3

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

Question 4

Describe Heptaic Type Glycogen Storage Disease

Answer 4

• 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

Question 5

What is the severe form of glycogen storage disease

Answer 5

Hepatic type glycogen storage disease

Question 6

What is the mild form of glycogen storage disease

Answer 6

Myopathic type glycogen storage disease

Question 7

Specific types of glycogen storage diseases and specific enzymes to Disease

Answer 7

Question 8

Groups of glycogen storage diseases

Answer 8

Question 9

Acid maltase???

Answer 9

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

Question 10

Pompe’s Disease

Question 11

Hers Disease

Question 12

McArdle’s Disease

Question 13

Cori’s Disease

Question 14

Von Gierke’s Disease

Question 15

Describe the overall function of the lysosome

Answer 15

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

Question 16

Describe Lysosomal Acidification

Answer 16

PRotein on surface of lysosome that starts out on an endosome called a VATPase which makes the lysosome acidic

Question 17

VATPase AKA

Answer 17

Vacuolar ATPase

Question 18

VATPase function

Answer 18

Basically a vacuolar ATPase which is involved in controlling pH of lysosomes by pumping protons against a gradient into the lysosome using ATP

Question 19

Why does the pH need to be so low in lysosomes?

Answer 19

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

Question 20

List of acid hydrolases in lysosomes

Answer 20

• Proteases
• Lipases
• Glycosidases
• DNAses
• RNAses

Question 21

Pathology of acid hydrolases

Answer 21

theses enzymes are made via transcription and constructed in the ER

Question 22

Describe The constitutive pathway

Question 23

Constitutive pathway AKA

Answer 23

Secretory pathway

Question 24

Describe lysosome synthesis

Answer 24

• 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

Question 26

Mucolipidosis description

Answer 26

class of lysosomal storage disease

Question 27

Mucolipidosis types

Answer 27

I-Cell Disease (Inclusion Cell)

Question 28

Describe I-Cell Disease

Answer 28

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

Question 29

I-Cell Disease prognosis

Answer 29

death in infancy

Question 30

Describe Niemann-Pick Disease

Answer 30

• Lipidosis lysosomal storage disease
• NPC1 is deficient so cannot process sphingolipids (primarily sphingomyelin) or no sphingomyelinase
• So you get a buildup of sphingolipids

Question 31

Fabry’s disease

Answer 31

Lipidosis lysosomal storage disease lacking α-Galactosidase so gangliosides build-up (primarily Gal-gal-glucosylceramide)

Question 32

Gaucher’s Disease

Answer 32

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)

Question 33

Tay-Sachs Disease

Answer 33

• Lipidosis Lysosomal Storage Disease
• Deficient in Hexosaminidase A
• Build up of gangliosides (primarily GM2 ganglioside)

Question 34

What are lipidoses?

Answer 34

Lysosomal storage diseases with the deficiency of an enzyme that degrades a type of glycolipids

Question 35

What is Mucopolysaccharidosis

Answer 35

Defects in glycosaminoglycans/proteoglycan degradation

Question 36

Common types of Mucopolysaccharidosis

Answer 36

• Hurler syndrome
• Hunter syndrome

Question 37

Describe Hurler Syndrome

Answer 37

Deficiencies of the enzymes will lead to accumulation of these structures in the lysosome

Question 38

Describe Hunter Syndrome

Answer 38

Question 39

Therapeutic options for storage diseases

Answer 39

Question 40

Learn all of these diseases and the enzymes and the symptoms and what happens etc, myb first aid