CH1- Biochemical Compounds

Adenosine deaminase deficiency

- Due to lack of adenosine deaminase, which converts
adenosine to inosine.
- Leads to accumulation of deoxyadenosine and Sadenosylhomocysteine, which are toxic to immature
lymphocytes in the thymus
- Inability to deaminate adenosine at position 6

Histidine has a side chain which could buffer in the range of 7.2
to 7.4

Gout
- Due to the buildup of uric acid in the blood, and
precipitation of uric acid in cold areas of the body.
- Uric acid has the basic ring structure of the purines and is
the degradative product of adenine and guanine

CH2- Protein Structure & Function

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Sickle Cell Anemia

- Substitution of Valine for glutamate at position 6 of the -chain.
This change, from a negatively charged amino acid side chain
(glutamate) to a hydrophobic side chain (Valine), allows
deoxygenated hemoglobin to polymerize and form long rods
within the red blood cells

Creutzfeldt-Jakob Disease
- Caused by a misfolded prion protein, leading to protein
aggregation in the brain.

Osteogenesis Imperfecta
- Due to a mutation in collagen, generating brittle bones
- Can be treated by taking bisphosphates, which decrease bone
resorption by the osteoclasts, thereby strengthening the bone.
Bisphosphates do not affect the synthesis of collagen or fibrillin

Primary Amyloidosis
- A protein folding disease in which immunoglobulin light chains
are improperly processed and cannot be degraded. These
proteins then form fibrils in tissues, which are insoluble.

Vitamin C is a required cofactor for prolyl hydroxylase, the

enzyme which hydroxylates proline residues in collagen

Cystic Fibrosis
- They have a thickening of the pancreatic duct, leading to
nutrient malabsorption, as pancreatic enzymes have difficulty
reaching the intestinal lumen. Lipid malabsorption syndromes
frequently lead to deficiencies in fat-soluble vitamin uptake (A, D,
E, K). Vitamin K is required for the carboxylation of glutamic acid
side chains on blood clotting factors

Myasthenia Gravis
- Antibodies are generated against the acetylcholine receptors
- Treatment with edrophonium chloride, which leads to a
transient increase in acetylcholine levels (through the temporary
inactivation of acetylcholinestarase)

Methemoglobinemia
- An increased percentage of +3 iron in the hemoglobin, a form
that cannot bind oxygen
- Can arise from mutation in methemoglobin reductase, which
will reduce the iron back to the +2 state

Duchenne Muscular Dystrophy

- Due to mutations in the protein dystrophin, found in the muscle
sarcolemma

Hereditary Spherocytosis
- A defect in spectrin in the erythrocyte membrane
- Leads to abnormal shape of the red blood cell, such that the
spleen removes them from circulation (resulting in large spleen),
leading to anemia

Huntington Disease
- Triplet repeats is expanded within the gene. These triplets
repeat codes for a polyglutamine tract in the mature protein

CH3- DNA Structure, Replication, and Repair

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3-5 exonuclease activity of DNA polymerase

- Examines for correct base-pairing properties

Fragile X syndrome
- Contains a triplet nucleotide repeat (CGG) on the X
chromosome in the 5 untranslated region of the FMRI gene.
The triplet repeats expansion leads to no expression of the
FMRI gene, which produces a protein required for brain
development.
- The X chromosome that carries the repeat expansion is subject
to DNA strand break under certain conditions (such as lack of
folic acid)

Xeroderma Pigmentosum
- A disorder in which thymine dimers (created by exposure to UV
light) cannot be appropriately repaired in DNA.
- Nucleotide excision repair enzymes recognize bulky distortions
in the helix

Uracil-DNA glycosylase system

- A repair system for when Cytosine spontaneously deaminates
to form uracil (C U)

Methotrexate
- An agent which inhibits dihydrofolate reductase and blocks the
synthesis of thymidine.

5-fluorouracil (5FU)
- An inhibitor of thymidylate synthase

Prader-Willi Syndrome
- Due to a deletion of a cluster of genes on chromosome 15
- Characteristics include hypotonia, insatiable appetite, and
obesity if food intake is uncontrolled

Bloom Syndrome
- A disease in which DNA helicase is defective
- People have skin that is sensitive to sun exposure

- Most are from Ashkenazi descent

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Cockayne Syndrome
- Due to a defect in transcription-coupled DNA repair
- Characterized by growth failure, impaired development of the
nervous system, abnormal sensitivity to sunlight, eye disorders
and premature aging

Hereditary nonpolyposis colon cancer

- Due to mutations in genes that are involved in DNA mismatch
repair

CH 4: RNA Synthesis
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Lupus
- An autoimmune disorder in which antibodies develop against
the snurps, small ribonuclear protein complexes
- Symptoms include fatigue, joint pain and butterfly rash

RNA Polymerase I synthesizes rRNA

RNA Polymerase II synthesizes mRNA
RNA Polymerase III synthesizes tRNA

Dactinomycin
- A drug that binds to DNA and blocks the ability of RNA
polymerase to transcribe genes, thereby blocking transcription

Rifampin
- A drug that binds to prokaryotic RNA polymerase but cannot
bind (due to the different structures of the RNA polymerase
between prokaryotic and eukaryotic cells) to eukaryotic RNA
polymerase

CH5: Protein Synthesis