Week 6: Lysosomal Storage Disorders and Membrane Lipid Synthesis Flashcards
What are lysosomes’ usual function, and how do “storage diseases” arise as it relates to them?
Lysosomes usually act to perform a digestive function in the body’s cells, breakind down complex components into simpler ones. When this process does NOT take place, some substrates can collect in cells (“storage diseases”). The symptoms of lysosomal storage disorders are usually progressive.
What are the two forms Tay-Sachs disease, and what are it’s symptoms?
Also known as GM-2-Gangliosidosis Type I, Tay-Sachs arises from two principal origins: infantile form and late-onset form. Symptoms include feeding problems, lethargy, an exaggerated startle reflex, and motor delays/mental deterioration.
What is Niemann-Pick disease, and what are it’s symptoms?
Niemann-Pick diseases are a group of inherited disorders related to fat metabolism. Certain traits common to all types (A/B, C1 and C2) include enlargement of the liver and spleen. Children with Types A or C also experience progressive loss of motor skills, feeding difficulties, progressive learning disabilities and seizures.
What is notable about Gaucher disease, and what are it’s symptoms?
It is the most common type of lysosomal storage disorder, and there are three types: type I (no neurological complications, type II and type III (varying extents of neural complications). Type I symptoms include easy bruising, chronic fatigue, and enlarged liver and/or spleen.
Type II occurs in newborns and infants, and is characterized by neurological complications that may include involuntary spasms, difficulty swallowing, and loss of motor skills.
Type III symptoms appear during the first decade of life, and include mental deterioration, inability to coordinate movement, and muscle spasms.
What are the types of Pompe disease, and what are their symptoms?
Pompe has an infantile form and a delayed onset form. Patients with the infantile form are the most severely affected, with rapidly progressive muscle weakness, hypotonia (diminished muscle tone), and hypertrophic cardiomyopathy (thickening of heart muscle, making it tough for the heart to pump blood.
What kind of disease is Hurler disease, and what are it’s symptoms?
Hurler disease is a mucopolysaccharide (MPS) storage disease, and is caused by the disturbance of complex carbohydrate (mucopolysaccharide) breakdown. These diseases convey symptoms of bone and joint deformeties and interference with growth, causing short stature.
How are the discussed lysosomal storage disorders inherited?
They are autosomal recessive
What treatments are available for Gaucher disease?
Miglustat (Zavesca) is available to treat Gaucher disease type I, and involves substrate reduction. There is also enzyme replacement therapy available.
What treatments are available for Hurler disease?
Bone marrow transplantation is effective if done early (before 2 years of age). Further, Aldurazyme acts to rebuild the capacity of the enzyme alpha L-iduronidase, which leads to a GAG buildup in MPS (mucopolysaccharide) in patients.
Explain the structural difference between glycerophospholipids and sphingolipids
Glycerophospholipids have a glycerol base, with two attached fatty acid chains. They also have a phosphate group esterified to a headgroup.
Sphingolipids have a sphingosine base (easy to identify because of NH3 group), with ONE fatty acid chain attached. They either have a phosphate group esterified to a headgroup, or a mono/oligosaccharide that may be phosphorylated.
What is the “common origin” of TAGs and glycerophospholipids? What is the difference between the two?
Phosphatidic acid. TAGs have three acyl groups esterified to the glycerol backgone, and glycerophospholipids have a phosphate group esterified to a head group on one branch of the glycerol backbone.
What are the two main ways DAGs are synthesized?
Either an -OH on the headgroup precursor attacks a phosphate group attached to the DAG precursor, or an -OH on the DAG precursor attacks a phosphate group attached to the headgroup precursor.
What health issue is caused by the incorrect synthesis of phosphatidylserine?
Respiratory Distress Syndrome, or RDS, where infants do not properly produce the surfactant needed to maintain the integrity of lung alveoli.
What is the theoretical benefit of plasmologens, and what makes them different from glycerophospholipids? What is an example of a plasmologen?
Instead of having two esterified acyl groups attached, the plasmologens have an ether-linked acyl group. This is thought to possibly protect against damage from ROS. Platelet-activating factor is an example of a plasmologen.
What are the four major steps to sphingolipid biosynthesis?
(1) Synthesis of sphingamine, an 18C amino alcohol
(2) Attachment of an FA via an amide bond
(3) Desaturation of the alkane chain of acylsphinganine (results in ceramide)
(4) Headgroup attachment
What are two critical biological roles of glycosphingolipids?
(1) They participate in cell surface structures associated with blood types
(2) Ganglioside GM1 is the receptor for choleratoxin in the human intestine
What enzyme is dysfunctional in Tay-Sachs disease?
Hexosaminidase A
What enzyme is dysfunctional in Niemann-Pick disease?
Sphingomyelinase
What enzyme is dysfunctional in Gaucher’s disease?
Glucocerebrosidase
