Term
| Name the vitamin derivative that is required for the prolyl hydroxylase reaction. |
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Definition
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Term
| Why is the element selenium essential? |
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Definition
| Selenium is essential to normal metabolism because it is necessary in the formation of Selenocysteine. Selenocysteine is needed to make glutathione peroxidases among other various selenoproteins. Selenocysteine is also used in the synthesis of selenocysteinyl-tRNA. |
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Term
| Describe in detail the pathway for the biosynthesis of SAM and cysteine. |
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Definition
The biosynthesis of SAM involves the substrates Methionine and ATP. The enzyme that catalyzes the reaction is Methionine Adenosyltransferase.
SAM is then converted to S-adenosylhomocysteine, catalyzed by Methyltransferase. S-adenosylhomocysteine is converted to Homocysteine, losing its adenosine group. Homocysteine is converted to Cystathionine. This reaction requires the enzyme Cystathionine Beta Synthase and Pyridoxal Phosphate (vitamin B6). Cystathionine is then converted to Cysteine and this reaction is catalyzed by Gamma Cystathionase and also requires Pyridoxal Phosphate (vitamin B6). |
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Term
Describe in detail the biochemical basis for the diseases:
a. phenylketonuria
b. alcaptonuria
c. albinism |
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Definition
a. Phenylalanine is converted to Tyrosine via the enzyme Phenylalanine Hydroxylase. The reaction also requires THB. Deficiency of this enzyme results in increased levels of Phenylalanine and this is excreted in the urine as phenylpyruvate and phenylketones. In some cases, deficiency of THB also causes PKU. Since tyrosine is no longer formed, those compounds that are related to tyrosine are also blocked in individuals with PKU.
b. Tyrosine is degraded into p-hydroxy phenylpyruvate. This is converted to Homogentisate via an oxidase. The Homogentisate is converted to Maleyl Acetoacetate via another oxidase. Deficiency of the Homogentisate Oxidase results in accumulation of Homogentisate or homogentisic acid. This compound is oxidized into a dark brown polymer and is deposited in joints, which causes arthritis.
c. Tyrosine through a series of reactions is also converted into Melanin. Involved in these reactions is the enzyme Tyrosinase. Melanin is responsible for skin pigmentation. In individuals with albinism, tyrosinase deficiency results in low melanin production, and the skin the becomes susceptible to the damaging effects of sunlight such as skin cancer. |
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Term
Describe in detail, the biochemical basis for the diseases:
a. homocystinuria
b. cystathionuria
c. cystinuria |
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Definition
All three of these diseases involve the following reaction:
Methionine is converted to SAM. SAM is converted to S-adenosylhomocysteine, which is converted to Homocysteine. Homocysteine is converted to Cystathionine via Cystationine Beta Synthase and Pyridoxal Phosphate. Cystathionine is converted to Cysteine via Gamma Cystathionase and Pyridoxal Phosphate.
a. Cystathionine Beta synthase deficiency causes homocysteine accumulation. Pyridoxal Phosphate deficiency can make the problem worse.
b. Caused by deficiency of the next enzyme involved in the pathway: Gamma Cystathionase. The accumulated Cystathionine is then excreted. This condition can also result from a deficiency of Pyridoxal Phosphate (vitamin B6). This disease is less problematic than Homocystinuria.
c. Cystinuria is due to a defect in membrane transport of dietary cysteine through epithelial cell membrane which results in the accumulation of cysteine in the urine. Cysteine gets oxidized into Cystine. Cystine has low solubility, so it precipitates out in the urinary tract forming kidney stones. |
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Term
Describe in detail the biochemical basis for the diseases:
a. maple syrup urine disease
b. histidinemia |
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Definition
a. Leucine is converted into Acetyl CoA via the enzyme Branched Chain Ketoacid Dehydrogenase. Valine and Isoleucine are converted into Propionyl CoA via the same enzyme. Deficiency in this enzyme causes MSUD.
b. Histidine metabolism involves the conversion of Histidine to Urocanate via the enzyme Histidase. Uroconate is then converted to Glutamate through a series of reactions.
Histidinemia is due to deficiency of the enzyme histidase. This enzyme is highly expressed in skin and liver. Therefore histidase deficiency can be confirmed using skin biopsies. As a side note, urocanate is a component of sweat. |
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Term
| Can folic acid be synthesized in humans? |
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Definition
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Term
| What step is inhibited by sulfamethoxazole? |
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Definition
| It inhibits the formation of Folic Acid from ParaAmino Benzoic Acid (PABA). This is the first step in the pathway to convert PABA to THF. |
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Term
| Describe in detail, the role of folate in relation to one carbon metabolism. |
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Definition
| Folate is converted to THF. One carbon units from amino acid degradation are added on to THF to form active folate. Active folate comes in three forms: Formyl THF, Methenyl THF, and Methylene THF. These all serve as a carrier for carbon atoms. They can be reduced to Methyl THF which is utilized in the conversion of Homocysteine to Methionine, and in so doing reforms THF. Formyl and Methylene THF are involved in Purine synthesis, Methylene THF is involved in Thymidine synthesis, and Methyl THF is involved in Methionine synthesis. |
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Term
| Describe the biosynthesis of carnitine. |
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Definition
| Lysine is converted to N-trimethyl Lysine. This reaction is catalyzed by Methyl Transferase and SAM. N-trimethyl Lysine is converted to Carnitine through a number of steps that Venk did not detail. |
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Term
| What are some organism specific dihydrofolate reductase inhibitors? |
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Definition
| DHFR is inhibited by Methotrexate which is very specific towards eukaryotes. Pyrimethamine is specific towards protozoans (amoeba). Epiroprim, a type of trimethoprim, is specific towards bacterial DHFR. All serve to inhibit the enzyme. |
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Term
| Trimethoprim, methotrexate, and pyrimethamine inhibits_______________(specify the organisms) |
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Definition
They all inhibit Dihydrofolate Reductase.
Trimethoprim in bacteria.
Methotrexate in eukaryotes.
Pyrimethamine in protozoans (amoeba) |
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