Biochemistry

Question 1

This is a monomeric protein and the primary oxygen storing protein in skeletal and cardiac muscle. When would it be found in the bloodstream?

Answer 1

Myoglobin

Will be found in bloodstream after muscle injury

Question 2

Describe the phenylalanine metabolism pathway, the products, enzymes, and cofactors.

Answer 2

Phenylalanine –> tyrosine (enzyme: phenylalanine hydroxylase)
Cofactor = BH4 –> BH2 with dihydrobiopterin reductase

Tyrosine –> DOPA (enzyme: tyrosine hydroxylase)
Same cofactor

DOPA –> dopamine (enzyme: DOPA decarboxylase)

Dopamine –> NE (enzyme: dopamine b-hydroxylase)

NE –> Epi (enzyme: phenylethanolamine-N-methyltransferase = PNMT)
Cofactor = S-adenosylmethionine –> S-adenosylhomocysteine

Question 3

What is deficient with classic PKU?
What else can be deficient with PKU?
What is the difference between the 2?

Answer 3

phenylalanine hydroxylase

Also see deficiency with dihydrobiopterin reductase

Difference is that with restricted diet and tyrosine supplementation, you should not see neurological sx and hyperprolactinemia with classic PKU. However, you will see this with DHBR deficiency, because even with tyrosine supplementation, you will have deficiencies in the following products because tyrosine hydroxylase also uses the same cofactor.

Question 4

What is maple syrup urine dz?

Answer 4

It is an AR dz due to errors in metabolism of branch chain amino acids (valine, leucine, isoleucine).
It smells like burnt sugar.
Pts present in first few days of life with hypertonia, lethargy, poor feeding, and irritability.

Question 5

What is the function of NADPH?

Answer 5

Generate reduced glutathione
Fatty acid, cholesterol, & steroid synthesis
Respiratory burst via NADPH oxidase

Question 6

What type of hormones are generated in the SER? Explain the process.

Answer 6

SER lipophilic products, including lipid, phospholipids, & Steroid derivatives.

Cholesterol is converted pregnenolone in the mitochondria & transferred to the SER, which enzymes (21-hydroxylase) that produce steroid hormones.

Question 7

What is the rate limiting step of fatty acid synthesis?

How can you inhibit B-oxidation by a high-carb, high-protein diet?

Answer 7

Acetyl-CoA –> Malonyl-CoA via acetyl-CoA carboxylase (cytosol)

Increases in Malonyl-CoA will lead to inhibition of carnitine acyltransferase, which will prevent transfer of fatty acids into the mitochondria for degradation.

Question 8

Name the insulin-dependent & independent GLUT receptors. Where are they located?

Answer 8

Insulin-dependent = GLUT-4
-Muscles & adipocytes

Insulin-independent = GLUT-1, 2, 3, 5

• 1 = Brain, RBCs
• 2 = hepatocytes, renal tubules, small intestine, Pancreatic B-cells
• 3 = placental & neuronal
• 5 = FRUCTOSE transporter in spermatocytes & GI tract

Question 9

What enzyme is deficient in Acute Intermittent Porphyria? What enzyme do you need to downregulate to treat AIP?

Answer 9

PBG deaminase - leads to accumulation of PBG ALA

downregulate ALA synthase to treat AIP (inhibited by Glucose & home)

Question 10

Describe the affect of 2-BPG on O2 and hemoglobin.

Answer 10

2-BPG binds strongly to B-subunit
Reduced affinity of O2 for hemoglobin allowing better perfusion of peripheral tissue

Decrease = LEFT shift = resembles HbF

Question 11

Sickling is promoted by?

Answer 11

Low O2 levels
Increased acidity
Low blood volume

Question 12

Protein change for sickle cell anemia?

For cystic fibrosis?

Answer 12

SCA = Val --> Glu 
CF = Phe deletion (F508)

Question 13

Vitamin deficiency with Isoniozid?

with antiepiletics?

Answer 13

Isoniozid = B6 def
Anti-epileptics = B9 def

Question 14

Hoe does CO2 poisoning affect hemoglobin?

Answer 14

Competitively binds heme Fe2+ with increased affinity generating carboxymethmoglobin (LEFT shift)

Question 15

How is the ATP generating step of glycolysis bypassed in RBCs?

Answer 15

The enzyme bisphosphoglycerate mutase will turn 1,3-BPG to 2,3-BPG

2,3-BPG + Phosphatase –> phosphoglycerate –> pyruvate

NO ATP GENERATED!

Question 16

Which type of RNA contains dihydrouridine, ribothymidine, pseudouridine and cytidine? Where on it? What is on the 3’ end?

Answer 16

TRNA!

dihydrouridine = d-loop (facilitate correct tRNA recognition by aminoacyl trna synthetase)

ribo, pseudo, and cytidine = cwt T-loop (necessary for binding to ribosome)

3’end = 5’ CCA 3’

Question 17

How does pyruvate kinase deficiency cause hemolytic anemia? What is observed in the spleen?

Answer 17

Failure of glycolysis and no ATP

Splenomegaly –> reticuloendothelial cells in the splenic red pulp = removal of damaged RBCs, increased activity in PKD causes hyperplasia

Question 18

What is the structure of collagen?

Answer 18

3 alpha chains held together by H-bonds
Form triple helices
Glycine-X-Y repetition

x =  usually proline
y = hydroxyproline or hydroxylysine

Question 19

Describe the RAS/MAPK pathway.

Answer 19

A ligand attaches to the tyrosine kinase receptor. It then autophosphorylates an inactive RAS-GDP into a active RAS-GTP, which will then activate MAP kinase.

Question 20

What is homocystinuria? Describe the features.

Answer 20

It is a defect of cystathionine synthase, which turns homocysteine (using serine) to cystathionine and eventually cysteine.

Features: 
Hypercoagulability
Thromboembolic occlusion
Premature ACS
Intellectual disability 
Ectopia lentis (ocular lens displacement)

Question 21

In bacteria, there are operons from which multiple enzymes can be made at one time. How?

Answer 21

Bacterial mRNA = polycistronic

One mRNA codes for several proteins