Introduction of Hydroxy amino acids
Introduction of Serine (Hydroxy amino acids)
- Aliphatic hydroxy amino acid.
- Non essential amino acid.
- Isolated by Cramer in 1865.
Serine Biosynthesis (Hydroxy amino acids)
- The main pathway to serine starts with the glycolytic intermediate 3-phosphoglycerate.
- An NADH-linked dehydrogenase converts 3-phosphoglycerate into a keto acid, 3-phosphopyruvate, suitable for subsequent transamination.
- Aminotransferase activity with glutamate as a donor produces 3-phosphoserine, which is converted to serine by phosphoserine phosphatase.
- The conversion of serine to glycine and then glycine oxidation to CO2 and NH3, with the production of two equivalents of N5, N10-methyleneTHF.
- Serine can also be converted to pyruvate through a deamination reaction catalyzed by serine dehydratase.
Functions of Serine
- Serine is involved in many anabolic reactions including the synthesis of
Threonine (Hydroxy amino acids)
The –OH group of threonine is a site for protein phosphorylation
SULPHUR CONTAINING AMINO ACIDS
Metabolism of Sulfur-containing AAs
METABOLISM OF METHIONINE
- Essential Glucogenic Amino Acid
- Catabolism: via being homocysteine, which is converted into homoserine (Trans-Sulfuration) and then ultimately into propionyl CoA Succinyl CoA.
– Trans-Methylation: is achieved by its role in formation of SAM by Methyl transferase.
– Polyamines synthesis.
– Cysteine synthesis and its derivatives.
- Methionine metabolism may be divided in to three parts
- Utilization of Methionine for transmethylation reactions.
- Conversion of Methionine to Cysteine and Cystine.
- Degradation of Cysteine and its conversion to specialized products.
- The transfer of methyl group (-CH3) from active methionine to an acceptor is known as transmethylation.
- Methionine has to be activated to S-adenosyl methionine or active methionine to donate the methyl group
Synthesis of S-Adenosylmethionine
- The synthesis of S-adenosylmethionine occurs by the transfer of an adenosyl group from ATP to sulfur atom of Methionine.
- This reaction is catalyzed by Methionine S-adenosyl transferase.
Condensation of ATP and methionine yield S-adenosylmethionine (SAM)
SAM serves as a precursor for numerous methyl transfer reactions (e.g. the conversion of norepinephrine to epinephrine).
Functions of S-adenosylmethionine (SAM)
- The SAM is highly reactive due to the presence of a positive charge.
- The enzymes involved in the transfer of methyl group are collectively known as methyltransferases.
- SAM is the direct donor of methyl in body. Methylation can synthesize many important materials such as: choline, creatine, etc.
- SAM is also involved in the synthesis of polyamines
Significance of Transmethylation
- Many compounds become active only after Methylation.
- Protein methylation helps to control protein turn over.
- In general, methylation protects the protein from immediate degradation.
S-adenosylmethionine (SAM) – a common methyl donor in the cell
•Non-Essential Glucogenic Amino Acid
- Catabolism: Into pyruvate
Significance of Cysteine Metabolism:
FORMATION OF GLUTATHIONE
- Glutathione is a tripeptide of glutamate, cysteine and glycine.
- • Glutathione is generally abbreviated as GSH.
Formation of PAPS
Synthesis of cystine
Homocysteine and Heart attacks
- Homocysteine is an intermediate in the Synthesis of cysteine from methionine.
- It is believed that homocysteine reacts with collagen to produce reactive free radicals, besides interfering with collagen cross links.
- Homocysteine is also involved in the aggregation of LDL particles.
- All this leads to an increase tendency
- For atherogenesis, and consequently Heart complications.
Homocysteine (< 15 μmol/L)
Hyperhomocysteinemia can results in:
- Vascular diseases, endothelial dysfunction, atherosclerosis
- Skeletal anomalies
- retardation of mental development
- Alzheimer’s disease
- Kidneys insufficiency
- Colorectal cancer
Inborn error of Sulfur containing Amino Acids
- One of the most common inherited disease with a frequency of 1 in 7, 000.
- Cystinuria is usually identified in the laboratory by cyanide nitroprusside test.
- Aminoacidopathy (Not a metabolic disorder)
- Caused by:
Defective renal re- absorption of dibasic amino acid
- Cystine precipitation Renal cystine stones
– Alkalanization of urine by Na2CO3
– Plenty of fluids
-D-penicillamine, captopril drugs can be used
- Also known as cysteine storage disease.
- Cysteine crystals are deposited in lysosomes of many tissues and organs of reticuloendothelial system through out the body.
- These include spleen, lymph nodes, liver, Kidney, bone marrow etc.
- Abnormality in the transport across lysosomal membranes
- First Described in 1962, these are the latest in the series of inborn error of metabolism.
- All of them are autosomal recessive conditions.
- Incidence is 1 in 200, 000 birth.
- Normal homocysteine level in blood is 5-15 micromol/liter.
- In disease it may be increased to 50 – 100 times.
- Homocystinuria is an inborn error of aminoacid metabolism in which accumulation and excretion of large amounts of homocysteine and SAM are seen
- Homocystinuria type I, due to deficiency of the enzyme cystathionine synthase, is the most common inborn error of methionine metabolism. It is characterized by mental retardation, lens dislocation, skeletal abnormalities and thrombotic vascular disease.
- Homocystinuria may also be due to defects in methyl cobalamin formation, i.e., Homocystinuria type II, characterized by the triad of megaloblastic anemia, homo-cystinuria and hypomethioninemia.
- Deficiency of the enzyme methyltetra-hydrofolate reductase, results in homo cystinuria type III, which is characterized by homocystinuria and homocystinemia with low or normal blood methionine levels.
Diet low in methionine and rich in cysteine
Other Biochemistry Notes
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