Biochemistry8-28

Question 1

What is the function of pantothenic acid in the Kreb (TCA) cycle?

Answer 1

Conversion of oxaloacetate to citrate

Pantothenic acid is converted into it’s biologically active form, coenzyme A. Coenzyme A binds oxaloacetate during the first step of TCA cycle and forms, first citrate, then succinyl-CoA.

Question 2

Clinical Manifestation:

Classic homocystinuria

Answer 2

Multiple phenotypic manifestations (Pleiotropy) including:

(1) ectopia lentis
(2) mental retardation
(3) marfanoid habitus
(4) osteoporosis
(5) vascular problems

Question 3

Describe a transamination reaction? What co-factor is required to complete this reaction?

Answer 3

Transamination reaction: Amino acid + alpha-keto acid –> alpha-keto acid + amino acid (the amino group is exchanged)
Required co-factor: pyridoxal phosphate (Vitamin B6/”pyridoxine”)

Question 4

What enzyme is deficient in Cori disease (glycogen storage disease type III)?

Answer 4

Debranching enzyme

Patients present with hypoglycemia, ketoacidosis, hepatomegaly, muscle weakness & hypotonia.

Question 5

How might you distinguish Cori disease from Von Gierke disease based on your patient’s clinical presentation?

Answer 5

Cori disease is associated with muscle weakness and hypotonia.

Question 6

Diagnosis:

Laboratory test reveal glycogen accumulation within lysosomal vacuoles

Answer 6

alpha-glucosidase deficiency (Pompe disease)

Question 7

Clinical Manifestation:

Pompe disease (glycogen storage disease type II/alpha-glucosidase deficiency)

Answer 7

in early infancy:
1. Cardiomegaly
2. Profound hypotonia
3. Macroglossia (poor feeding)

Question 8

Where does the metabolic pathway that uses transketolase occur?

Answer 8

The pentose-phosphate shunt (HMP shunt) utilizes transketolase. This process occurs in the cytoplasm.

The HMP shunt is responsible for generating NADPH.

Question 9

Autosomal dominant vs. Autosomal recessive

Most enzymatic disorders are…

Answer 9

Autosomal recessive

Question 10

What is the function of 3’ to 5’ exonuclease activity?

Answer 10

3’ to 5’ exonuclease activity allows DNA polymerase to proofread.

Question 11

Which step in collagen synthesis is dependent on vitamin C?

Answer 11

Hydroxylation of proline and lysine residues

Question 12

Clinical Manifestation:

Vitamin C deficiency (scurvy)

Answer 12

1. gingival bleeding (capillary bleeding)
2. ecchymosis
3. petechia
4. poor wound healing
5. perifollicular hemorrhages & coiled (corkscrew) hairs

Children may have bony deformities and subperiosteal hemorrhages.

Question 13

Treatment:

A patient with a urea cycle deficiency

Answer 13

Urea cycle defects result in the build up of ammonia.To treat:

1. Limit protein intake (ammonia is generated from the metabolism of alpha amino acids)

Medications that provide alternative pathways for ammnia removal can be combined with protein restriction.

Question 14

How are thymidine dimers created by UV exposure removed in humans?

Answer 14

UV-endonucleases excise the dimer.

This enzyme is missing in patients with xeroderma pigmentosa. These patients would present with (1) photosensitivity (2) poikiloderma (3) hyperpigmentation in sun-exposed areas and (4) and increased risk for devleoping skin cancer

Question 15

Pathogenesis:

Lynch syndrome (hereditary nonpolyposis colon cancer)

Answer 15

1. mutation in MSH2 or MLH1 gene
2. human MutS and MutL homologs are not properly formed
3. DNA mismatch repair is defective

Mutations in MSH2 or MLH1 account for 90% of Lynch syndrome cases. Lynch syndrome is autosomal dominant.

Question 16

What coenzyme do the following enzymes share: (1) transketolase (2) alpha-ketoglutarate dehydrogenase (3) pyruvate dehydrogenase

Answer 16

Thiamine (vitamin B1)

Question 17

What is the rate limiting step in glycolysis?

Answer 17

Fructose 6-phosphate conversion to Fructose 1, 6-bisphosphate via PFK-1.

Question 18

Why does fructose have the highest rate of metabolism in the glycolytic pathway?

Answer 18

Fructose can be metabolized into Fructose 1-phosphate in the liver (via Fructokinase). From here it is converted into DHAP and Glyceraldehyde (via Aldolase B) and resumes the remainder of the glycolytic pathway. Overall, it bypasses the rate limiting step of glycolysis (PFK-1).

Question 19

Glucogenic/Ketogenic

Which type of diet would benefit a patient with a pyruvate dehydrogenase (PDH) deficiency?

Answer 19

Ketogenic

A person deficient in PDH would have a build up of lactic acid due to an inability to convert pyruvate to acetyl CoA. They would most benefit from a diet that is exclusively ketogenic and would not increase blood lactate levels.

Question 20

Which metabolic enzymes share the following coenzymes:

(1) Thiamine
(2) Lipoic acid
(3) CoA, FAD, NAD+

Answer 20

1. pyruvate dehydrogenase
2. _-ketoglutarate dehydrogenase complex

Question 21

Which mitochondrial enzymes require lipoic acid as a cofactor? What disease might result in patients with a deficiency?

Answer 21

1. Pyruvate dehydrogenase –> lactic acidosis
2. _-ketoglutarate dehydrogenase –> maple syrup urine disease
3. branched-chain ketoacid dehydrogenase–>maple syrup urine disease

Question 22

Which amino acids are exclusively ketogenic?

Answer 22

1. Leucine
2. Lysine

*These amino acids would be preferred in the diet of a pateint with pyruvate dehydrogenase deficiency.

Question 23

How are branched chain amino acids (i.e. Valine, Leucine, Isoleucine) metabolized?

Answer 23

1. The amino acids are transaminated into their respective alpha-ketoacids
2. The alpha-ketoacids are then metabolized by branched-chain alpha-ketoacid dehydrogenase