B&B Biochemistry Flashcards by Joel Glotfelty

Located in nucleus of eukaryotic cells

-Contains genetic code

DNA

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Located in cytoplasm of prokaryotic cells

DNA

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The DNA structure is composed of

Sugar (ribose) backbone, Nitrogenous base, phosphate

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Made up of a pentose sugar, nitrogenous base, and phosphate group

Nucleotide

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What if the difference between nucleotides and nucleosides?

Nucleotides have a phosphate group

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Synthesized as monophosphates and then converted to triphosphate form

Nucleotides

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Occurs in segments with GC patterns (GC Islands)

DNA methylation

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Inactivates transcription

DNA Methylation

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Unmethylated GC stimulates an

Immune Response

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Bacteria methylate

Cytosine and adenine

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Methylation protects bacteria from

Viruses (phages)

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In bacteria, non-methylated DNA is destroyed by

Endonucleases

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Found in nucleus of eukaryotic cells

-DNA plus proteins

Chromatin

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Units of histones plus DNA

Nucleosome

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Histones contain basic amino acids with high content of

Lysine and arginine

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Positively charged and binds to the negatively charged phosphate backbone

Histones

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Distinct from other Histones because it is not in the nucleosome core.

-Larger and more basic

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Fever, joint pains, and rash after starting a drug

Drug-induced lupus

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Caused by anti-histone antibodies in 95% of cases

Drug-induced lupus

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Classic lupus is caused by

anti-dsDNA

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What are the three classic drugs that cause drug-induced Lupus?

Hydralazine, Procainamide, and Isoniazid

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Condensed chromatin where DNA sequences are not transcribed

-Significant DNA methylation

Heterochromatin

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Less condensed form of chromatin

-Transcriptively active

Euchromatin

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In heterochromatin, we see significant

DNA methylation

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In euchromatin, we see significant

Histone Acetylation

Acyl group is added to lysine, which relaxes the chromatin for transcription

Histone acetylation

We see increased expression of some histone deacetylases in some

Tumors

What are two things that histone deacetylase inhibitors are used for?

Anti-cancer and Huntington's

A possible mechanism for Huntington's disease is

Histone Deacetylation

cAMP levels mediate

Blood flow

cGMP often serves as a

Secondary messenger

RNA is synthesized first and then is later converted to

DNA

The goal of purine synthesis is to create

AMP and GMP

Step 1 of purine synthesis is to create

PRPP

Then, step 2 of purine synthesis is to create

IMP

What are the three nitrogen sources from purine synthesis?

Aspartate, Glycine, and Glutamate

What are the three carbon sources during purine synthesis?

CO2, Glycine, and Tetrahydrofolate

A major contributor to the formation of purines is

Folate

IMP is then used to create

AMP and GMP

Purine synthesis starts with ribose phosphate from the

HMP shunt

Converts ribonucleotides to deoxyribonucleotides

Ribonucleotide Reductase

Inhibits IMP dehydrogenase -Blocks the conversion of IMP to GMP

Ribavirin

Ribavirin inhibits the synthesis of

Guanine nucleotides (purines)

An immunosuppressant that inhibits IMP dehydrogenase

Mycophenolate

Slavages the bases adenine guanine, and hypoxanthine

Purine Salvage

Purine salvage requires

PRPP

In the purine salvage pathway, hypoxanthine and guanine are converted to IMP and GMP respectively by

HGPRT

In the purine salvage pathway, adenine is converted to AMP by

APRT (Adenine phosphoribosyl transferase)

A chemotherapy agent that mimics hypoxanthine and guanine

6-Mercaptopurine

Added to PRPP by HGPRT to create Thioinosinic acid

6-Mercaptopurine

The overall effect of 6-Mercaptopurine is a decrease in

IMP, AMP, and GMP

An immunosuppressant that is converted to 6-MP

Azathioprine

In the purine breakdown pathway, hypoxanthine is converted to Xanthine by

Xanthine Oxidase

In the purine breakdown pathway, Guanine is converted to Xanthine by

Guanase

Then, Xanthine (from hypoxanthine and guanine) is converted to uric acid by

Xanthine oxidase

Crystal deposition in joints caused by excess uric acid

Gout

Can occur from high cell turnover (trauma or chemo) and consumption of purine-rich foods like meat and seafood

Gout

The treatment for gout is

Xanthine oxidase inhibitor (Allopurinol)

Azathioprine and 6-MP are metabolized by

Xanthine oxidase

May boost effects of 6-MP and increase toxicity of the drug

Co-treatment with allopurinol

X-linked absence of HGPRT -results in excess uric acid production

Lesch-Nyhan Syndrome

In Lesch-Nyhan syndrome, we see excess denovo purine synthesis, which means increases in

PRPP and IMP

The classic presenting feature of Lesch-Nyhan Syndrome is

Self-mutilating behavior

A male child with motor symptoms, self mutilation, and gout, is the classic presentation of

Lesch-Nyhan Syndrome

The goal of pyrimidine synthesis is to create

CMP, UMP, and TMP

Step one of pyrimidine synthesis is to make

Carbamoyl phosphate

In step one of pyrimidine synthesis, it is important to note that

Ring is formed first, then ribose is added

Step 2 of pyrimidine synthesis is to make

Orotic Acid

Step 3 of pyrimidine synthesis is to make

UMP

Orotic acid and PRPP are combined to make UMP by

UMP synthase

The key point of pyrimidine synthesis is that UMP is synthesized first and the from UMP we derive

CMP and TMP

The pryimidine ring is made up of

2 Nitrogens and 4 Carbons

3 carbons and 1 nitrogen of the pyrimidine ring are derived from

Aspartate

1 nitrogen and 1 carbon of the pyrimidine ring are derived from

Carbamoyl Phosphate

Autosomal recessive disorder caused by a defect in UMP Synthase

Orotic Aciduria

Orotic aciduria is characterized by a loss of pyrimidines and a buildup or

Orotic Acid

What are 3 key findings of Orotic Aciduria?

1. ) Orotic acid 2. ) Megaloblastic Anemia 3. ) No B12/Folate response 4. ) Growth Retardation

How do we treat Orotic Aciduria and what is the effect of this treatment?

Treat with Uridine -Bypasses UMP synthase

Key urea cycle enzyme, which functions to combine carbamoyl phosphate with ornithine

Ornithine TransCarbamoylase (OTC)

OTC combines carbamoyl phosphate w/ ornithine to make

Citrulline

OTC deficiency results in increased carbamoyl phosphate which causes increases in

Orotic Acid

We want to be careful not to confuse OTC deficiency with

Orotic aciduria

How do we distinguish between OTC deficiency and orotic aciduria?

OTC has increased ammonia levels

B&B Biochemistry Flashcards

(83 cards)