Term
| What do oligodendrocytes do? |
|
Definition
|
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Term
|
Definition
| Provide metabolic support and protection for neurons |
|
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Term
| What type of cells line the ventricles and are involved with making CSF? |
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Definition
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|
Term
| What are the two glucose transporters in the brain? |
|
Definition
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Term
| What enzyme is deficient in PKU, and what is the major symptom? |
|
Definition
Phenylalanine Hydroxylase
Mental Retardation
-also deficiency in pigmentation due to reduced melanin |
|
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Term
| Tyrosine is required to make what? |
|
Definition
| Catecholamine Neurotransmitters |
|
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Term
| What is the principal fuel source of the brain during starvation? |
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Definition
| Ketone bodies, which can be absorbed readily |
|
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Term
| Why is the effect of insulin overdose seen in a very few minutes? |
|
Definition
| Brain contains very little glycogen |
|
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Term
| What are the two principal reasons the brain requires energy? |
|
Definition
Transport- to maintain ion gradient and electrochemical potential in neurons
Synthesis of neurotransmitters |
|
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Term
| What is the principal source of energy for the brain in the first 24 hours of starvation? |
|
Definition
| Glucose- from gluconeogenesis |
|
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Term
| Besides its use for energy, name 3 other requirements for glucose in the brain: |
|
Definition
-Synthesis of acetylcholine
-Synthesis of glutamate and GABA
-Substrate for the pentose phosphate pathway to MAKE NADPH |
|
|
Term
| What is NADPH required for? |
|
Definition
Fatty acid synthesis
Glutathione Reductase Activity for antioxidant defense |
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Term
| Sphingolipids are derived from________ and contain________. |
|
Definition
Sphingosine (an alcohol)
Ceramide (a fatty acid derivative of sphingosine) |
|
|
Term
| What are the two types of sphingolipids? |
|
Definition
Sphingomyelin
Glycosphingolipids |
|
|
Term
| What is a major component of neuronal membranes? |
|
Definition
|
|
Term
| What accumulates in Neimann-Pick Disease? |
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Definition
| Sphingomyelin and cholesterol |
|
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Term
| Type A and B Neimann Pick are due to a deficiency of what enzyme? What is the accumulated product, and where does it accumulate? |
|
Definition
Sphingomyelinase,
Sphingomyelin,
Brain, Liver, and Spleen |
|
|
Term
| What is the most common type of Neimann-Pick disease, and in what population is it most prevalent? |
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Definition
| Type A is most common, rare outside of ASHKENAZI JEWISH POPULATION |
|
|
Term
| Types C and D Neimann Pick are due to what and result in the accumulation of what? |
|
Definition
Due to a defect in lipid transport
Result in accumulation of CHOLESTEROL |
|
|
Term
| What makes up a glycosphingolipid? |
|
Definition
Ceramide and at least one sugar residue
(Compare to sphingomyelin- ceramide+ phosphoryl choline) |
|
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Term
| What compounds, containing a single sugar residue (glucose or galactose) are particularly prominent in the myeling sheath? |
|
Definition
Cerebrosides
GALACTOCEREBROSIDE, GLUCOCEREBROSIDE |
|
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Term
| What enzyme is deficient in Gaucher disease and what accumulates? |
|
Definition
Beta glucosidase is deficient
GLUCOCEREBROSIDE accumulates |
|
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Term
| What gets damaged due to accumulations of stuff in Gaucher disease, and what is the stuff? |
|
Definition
| Bone marrow, liver, and spleen get damaged by accumulation of Glucocerebroside causing enlarged cells (Gaucher Cells) |
|
|
Term
| What are the 3 types of Gaucher, and what is their brain involvement? |
|
Definition
Type 1- chronic, non-neuropathic- mild and treatable
Type 2- Acute neuropathic- rapidly progressive, death within 2 years
Type 3- Subacute neuropathic- presents in childhood- death in 2-60 years
Brain unaffected in Type 1, most affected in Type 2, less in Type 3 |
|
|
Term
| What is the MOST COMMON sphingolipidosis? |
|
Definition
|
|
Term
| How are Type 1 and Type 3 Gaucher treated? |
|
Definition
| Enzyme replacement therapy (of Beta Glucosidase) |
|
|
Term
| What is deficient in Krabbe disease, and what accumulates? |
|
Definition
Beta Galactosidase is deficient and galactocerbroside accumulates
DEMYELINATION |
|
|
Term
| What is the pathology of Krabbe disease? |
|
Definition
| Macrophages aggregate forming GIANT CELLS called GLOBOID CELLS around blood vessels |
|
|
Term
| What is deficient in Fabry disease, and what accumulates? |
|
Definition
| Alpha Galactosidase A is deficient, and ceramide trihexoside accumulates |
|
|
Term
| How is Fabry disease treated? |
|
Definition
| Enzyme replacement therapy- Alpha Galactosidase A |
|
|
Term
| What is Metachromatic Leukodystrophy? |
|
Definition
| Accumulation of sulfatide due to deficiency of lysosomal sulphatase |
|
|
Term
|
Definition
| Galactocerbroside with a sulphate attached |
|
|
Term
| What composes a ganglioside? |
|
Definition
| Several sugar residues and one or more neuraminic acid residues (N-acetyl neuraminic acid which is also sialic acid) NA NANANA NA NANANA NANA |
|
|
Term
| What enzyme is deficient in Tay Sachs disease, and what accumulates? |
|
Definition
Hexosaminidase A deficiency
Ganglioside GM2 accumulates |
|
|
Term
| All sphingolipidoses are inherited via _______ _______ inheritence, except for _____ which is ________. |
|
Definition
Autosomal Recessive
Except for Fabry's, which is X-linked |
|
|
Term
| What are (currently) the only two treatable sphingolipidoses? |
|
Definition
| Gaucher and Fabry- enzyme replacement therapy |
|
|
Term
| What are the two reactions for which Vitamin B12 is required as a coenzyme? |
|
Definition
1) Methylmalonyl CoA Mutase Reaction- to make branched chain amino acids
2) Conversion of homocysteine to methionine with concomitant conversion of N5-methyl-tetrahydrofolate to tetrahydrofolate |
|
|
Term
| What characterizes vitamin B12 deficiency? |
|
Definition
| Megaloblastic anemia and neurological deterioration |
|
|
Term
| Why does vitamin B12 deficiency cause neurological disorders? |
|
Definition
| Progressive demyelination- accumulation of methylmalonyl CoA interferes with myelin sheath formation |
|
|
Term
| What are the two ways that accumulation of Methylmalonyl CoA (a consequence of B12 deficiency) interferes with myelin sheath formation? |
|
Definition
- competitive inhibitions of malonyl CoA carboxylase, a key step in FA formation to make myelin
-it substitutes for malonyl CoA in FA synthesis, making branched chain AA's that disrupt membrane structure |
|
|
Term
| Why does megaloblastic anemia occur in vitamin B12 deficiency? |
|
Definition
| Folate is trapped as N5-methyl tetrahydrofolate and cannot perform in normal purine synthesis |
|
|
Term
| What is the result of abnormally high levels of ammonia? |
|
Definition
| Toxicity to CNS- coma and death |
|
|
Term
| How does the brain remove ammonia? |
|
Definition
| Glutamine synthase reaction, which converts glutamate to glutamine |
|
|
Term
| What does the glutamine synthase reaction do, and why is it important? |
|
Definition
Converts glutamate to glutamine
Removes ammonia from the CNS |
|
|
Term
| What does accumulation of glutamine cause? |
|
Definition
|
|
Term
| Why are there no aspirins in the jungle? |
|
Definition
Because the parrots-ate-em-all
yuk yuk yuk |
|
|
Term
| What happens to the TCA cycle with high levels of ammonia? |
|
Definition
Alpha Ketoglutarate is removed by transamination to glutamate for the glutamate synthetase reaction
-this depletes ATP |
|
|
Term
| What enzyme is deficient in Congenital Hyperammonaemia Type I? |
|
Definition
| Carbamoyl Phosphate Synthetase |
|
|
Term
| What enzyme is deficient in Congenital Hyperammonaemia Type II? |
|
Definition
| Ornithine Transcarbamoylase |
|
|
Term
| What deficiency is the most common urea cycle genetic defect? |
|
Definition
| Ornithine transcarbamoylase deficiency- Congenital Hyperammonaemia Type II |
|
|
Term
| What are the symptoms of urea cycle genetic defects? |
|
Definition
| Episodic vomiting, psychomotor retardation, stupor |
|
|
Term
| How can urea cycle deficiencies be treated? |
|
Definition
|
|
Term
| What is distinctive about Gaucher disease histologically? |
|
Definition
| Gaucher cells have a crumpled tissue paper appearance |
|
|
Term
| What are the symptoms of Tay-Sachs? |
|
Definition
Mental retardation, blindness, death in infancy
CHARACTERISTIC RED SPOT ON MACULA |
|
|
Term
| How are Type I and Type II congenital hyperammonemia transmitted? |
|
Definition
Type I- Autosomal Recessive
Type II- X-linked |
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