Biochem: Metabolic Profile----> Brain

Question 1

Name the two types of glucose transporters found in the CNS.

Answer 1

1. GLUT-1: main glucose transporter found in all of the blood barriers in the body
2. GLUT-3: glucose transporter found in brain neurons.

(both have a low Km which correlates with a high affinity for glucose)

Question 2

Why do athletic drinks contain higher levels of branched chain amino acids?

Answer 2

During extrenuous exercise (like morons that run really long distance) glycogen stores are used up and the body mobilizes fatty acids (FA) for energy.

In order for the FA to be transported thru the body they need to bind to blood albumins. Binding to these blood albumins displaces the Tryptophan that was originally bound.

The Trp then circulates into the brain where it is metabolized to serotonin and melatonin which induces fatigue and drowsiness.

Branched chain AA compete with Trp for receptor sites and delay the fatigue.

Question 3

Enzyme deficient in Phenylketonuria.

Answer 3

Phenylalanine Hydroxylase (PAH)

-if you look at structures the only difference between Phe and Tyr is an -OH group on the benzene functional group in Tyr.

Question 4

Why is the liver the only organ that makes ketone bodies AND the only organ that cannot use them?

Answer 4

It is the only one that contains the enzymes to make the ketones bodies from Acetyl CoA.

The liver cannot use ketone bodies because:

1. Ketone bodies are metabolized back to Acetyl CoA for energy use by tissues.
2. In order for Acetyl CoA to enter the TCA cycle it must combine with Oxaloacetate (OAA).
3. All the OAA is depleted in the liver because OAA is used to make glucose in gluconeogenesis.
4. Therefore the Acetyl CoA cannot enter the TCA cycle because there is no OAA.

Question 5

What chemical messengers are made from glucose and used in the CNS? (4)

Answer 5

1. Glutamate
2. GABA
3. Glutathione (antioxidant)
4. ACh (glucose converted to Acetyl CoA)

Question 6

Glycosphingolipid that accumulates in Gaucher Disease.

Answer 6

Glucocerebroside (glucose+ceramide)

glucocerebrosidase is deficient enzyme

Question 7

Glycosphingolipid that accumulates in Krabbe’s Disease.

Answer 7

Galactocerebroside (galactose+ceramide)

Question 8

Glycosphingolipid that accumulates in Metachromatic Leukodystrophy.

Answer 8

Sulphatides (ceramides with a sulfur-containing galactose)

Question 9

Glycosphingolipid that accumulates in Tay Sach’s Disease.

Answer 9

GM2 Ganglioside

Question 10

Sphingolipid that accumulates in Fabry disease.

Answer 10

alpha-galactosidase A

X-linked disease

Question 11

Sphingolipid that accumulates in Niemann Pick Disease Type A and B.

Answer 11

Sphingomyelin

sphingomyelinase is deficient enzyme

Question 12

Diagnostic feature on physical exam that indicates Tay Sachs.

Answer 12

Cherry Red Spot on the macula

Question 13

Histologic appearance of Gaucher cells in patients with Gaucher Disease.

Answer 13

Crumpled Tissue Paper

Question 14

What are the two variants of Gaucher Disease?

Answer 14

Type 1: non-neuropathic, affecting adults and is chronic.

Type 2: neuropathic, affects infants.

Question 15

Treatment for Gaucher Type 1 and Fabry’s Disease.

Answer 15

1. Gaucher’s: IV glucocerebrosidase (Cerezyme)

2. Fabry’s: IV alpha-galactosidase A (Fabrazyme)

Question 16

What two reactions require Vitamin B12?

Answer 16

1. Homocysteine———–> methionine
   - converts folate into its active form (tetrahydrofolate) which is required to make nucleotides for DNA synthesis.
2. Methylmalanyl CoA——->Succinyl CoA
   - S CoA is a required intermediate for the TCA cycle. Also methylmalanyl CoA is metabolized into toxic products that harm the brain.

Result in Megaloblastic Anemia

Question 17

How is excess ammonia removed from the Brain to prevent neurotoxicity?

Answer 17

Glutamate can combine with ammonia to become glutamine using the enzyme glutamine synthetase.

Glutamine is a neutral and non-reactive molecule that can carry the ammonia to the liver where it can be transfered to urea and excreted.

Question 18

How is excess ammonia toxic to the brain?

Answer 18

The brain removes the ammonia using glutamate.

In order to make glutamate, the brain converts alpha-ketoglutarate into glutamate.

Alpha ketoglutarate is made from glucose.

In order to make enough alpha ketoglutarate the brain must use a lot of glucose which depletes its glucose supply and increases glutamine concentration which can lead to increased mitochondrial permeability and cerebral edema.

Question 19

Name two hereditary causes of hyperammonemia and one acquired cause.

Answer 19

1. Carbamoyl Phosphate Synthetase deficiency (autosomal urea cycle disease)
2. Ornithine Transcarbamoylase deficiency (X-linked urea cycle disorder)
3. Liver Disease (acquired)