Protein and A. Acids Metabolism part 2 Dr. Basema Sadiq Jaff Assist Protein and A.Acids Metabolism part 2 Dr. Basema Sadiq Jaff Assist. Professor,

F ates of C skeletons of 20 amino acids. Two are ketogenic: leucine & lysine. Nine are glucogenic. Nine are both because they form pyruvate or have two different degradation products.

Amino Acid Biosynthesis Essential amino acids can be made by plants & bacteria in 7 to 10 steps. We obtain these amino acids by eating plants. 11 Non-essential amino acids synthesized in 1 to 3 steps. Use glycolysis intermediates: 3-phosphoglycerate & pyruvate Krebs cycle intermediates: Oxaloacetate & a-ketoglutarate

Alanine, aspartate, & glutamate use transamination Starting materials for biosynthesis of 11 nonessential amino acids: 1 step, 2 steps, or 3 steps Alanine, aspartate, & glutamate use transamination

Amino acids that form oxaloacetate CATABOLISM OF THE CARBON SKELETONS OF AMINO ACIDS. Amino acids that form oxaloacetate asparagine an essential a.a for these cells, which therefore require asparagine from the blood. Aspara ginase, which hydrolyzes asparagine to aspartate, can be administered systemically to treat leukemic patients.Asparaginase↓ the level of asparagine in the plasma, deprives cancer cells of a required nutrient.

Amino acids that form α-ketoglutarate via glutamate; 1. Glutamine:2. Proline:3. Arginine:4. Histidine:This amino acidis oxidatively deaminated by histidase to urocanic acid, which subsequently forms N-formimino glutamate FIGlu donates its formimino group to tetra -hydro folate (THF), leaving glutamate, is Individuals deficient in folic acid excrete ↑ amounts of FIGlu in the urine, particularly after ingestion of a large dose of histidine.

Biosynthesis of thyroxine and tri-iodothyroxine The hormones thyroxine (T4) and tri-iodothyroxine (T3) are formed in the follicle cells of the thyroid gland by iodination of tyrosine residues of protein thyroglobulin. Monoiodo and diiodotyrosine residues are first formed and these then react to form T3 and T4

Amino acids that form pyruvate Alanine: Serine: Glycine 4. Cystine

2. Inherited deficiencies: Inherited deficiencies in the enzymes of : Amino acids that form fumarate Phenylalanine And tyrosine:Hydroxylation of phe produces tyr catalyzed by tetra -hydrobiopterin-requiring phenylalanine hydroxylase, catabolism of phe leading ultimately to the formation of fumarate and acetoacetate. 2. Inherited deficiencies: Inherited deficiencies in the enzymes of phe and tyr metabolism lead to the diseases phenylketonuria , alkaptonuria, and albinism

Amino acids that form succinyl CoA: Methionine is one of four amino acids that form succinyl CoA. This sulfur-containing amino acid deserves special attention because it is converted to S-adenosyl methionine (SAM), the major methyl-group donor in one-carbon metabolism .Methionine is the source of homocysteine—a metabolite associated with atherosclerotic vascular disease

Relationship of homocysteine to vascular disease: Elevations in plasma homocysteine levels promote oxidative damage, inflammation, and endothelial dysfunction, and are an independent risk factor for occlusive vascular disease. plasma Homocysteine levels are inversely related to plasma levels of folate, B12, and B6— involved in the conversion of homocysteine to methionine or cysteine. Large elevations in plasma homocysteine as a result of rare .deficiencies in cystathionine β-synthase are seen in patients with classic homocystinuria. These individuals experience premature vascular disease, with about 25% dying from thrombotic complications before 30 years of age.

Amino acids that form succinyl CoA Degradation of valine, isoleucine, and threonine also results in the production of succinyl CoA—a (TCA) cycle intermediate. 1. Valine and isoleucine: are branched-chain amino acids that generate propionyl CoA, which is converted to succinyl CoA by biotin- and vitamin B12–requiring reactions. 2. Threonine: dehydrated toα-ketobutyrate, which is converted to propionyl CoA and then to succinyl CoA. Threonine can also be converted to pyruvate.

Maple syrup urine disease (MSUD); is a recessive disorder in which there is a partial or complete deficiency in branched-chain α-keto acid dehydrogenase—an enzyme that decarboxylates leucine, isoleucine, and valine. Symptoms include feeding problems, vomiting, dehydration, severe metabolic acidosis, and a characteristic smell of the urine. If untreated, the disease leads to mental retardation, physical disabilities, and death. Treatment of MSUD involves a synthetic formula that contains limited amounts of leucine, isoleucine, and valine.

patients with PKU suffer from mental retardation, failure to walk or talk, seizures,hyperactivity, tremor, microcephaly, failure to grow and a characteristic smell of the urine. Treatment involves controlling dietary phenyl -alanine.

Case History A 5-month-old female infant was hospitalized. A diagnosis of classic phenylketonuria (PKU) was made. Questions a. Name the defective enzyme of classic phenylketonuria. b. Name the other types of PKU with their defective enzymes. c. What are the characteristics of PKU? d. Name diagnostic test for PKU

Albinism conditions in which a defect in tyrosine metabolism results indeficiency in the production of melanin. partial or full absence of pigment from the skin, hair, and eyes Albinism appears in different forms, and it may be inherited by one of several modes: autosomal Recessive (primary mode), autosomal dominant, or X-linked. Complete albinism (tyrosinase-negative oculocutaneous albinism) a deficiency of copper-requiring tyrosinase, hypopigmentation, vision defects anphotophobia . ↑ risk for skin cancer.

Tyrosine serves as a precursor for following several Biologically Important Compounds Tyrosine serves as a precursor for following several 1. Catecholamines – Dopamine – Norepinephrine – Epinephrine 2. Melanin pigment 3. Thyroxine.

Serotonin • Serotonin is synthesized from tryptophan cells. In normal adult, about 1% of tryptophan is converted to serotonin. Functions of serotonin • Serotonin is a neurotransmitter and stimulates cerebral activity. serotonin deficiency leads to depression. • serotonin is involved in a variety of behavioral patterns, including sleep, body temperature and blood pressure,intestinal cells stimulates the release of gastrointestinal peptide hormones. • Serotonin serves as precursor of melatoninin the pineal gland. • Serotonin is also a powerful vasoconstrictor and stimulator of smooth muscle contraction

These one carbon groups are transferred by way of tetrahydrofolate (THF). Tetrahydrafolate is formed from vitamin folic acid . It should be noted that CO2is also a one carbon group, is carried by vitamin biotin.

Importance of Glutamic Acid • A number of other amino acids like glutamine, proline and arginine are derived from glutamate. • Glutamate involved in the synthesis of glutathione, (γ-glutamyl-cysteinyl glycine) which is involved in the reduction of H2O2to H2O and transport of amino acids into cells of kidney and intestine. • Glutamate is decarboxylated at C-1 to form amine gamma aminobutyric acid (GABA), which serves as a neurotransmitter

1. Which of the following does not take part in thehuman urea cycle 1. Which of the following does not take part in thehuman urea cycle? a) Arginine b) Aspartate c) Arginosuccinate d) Urease 2. Which type of reaction is conversion of norepinephrine to epinephrine? a-Transamination b) Decarboxylation c) Transmethylation d) Phosphorylation 3. Phenylketonuria results due to the absence of the enzyme: a) Phenylalanine oxidase b) Phenylalanine hydroxylase c) Phenylalanine transaminase d) Phenylalanine oxygenase 4. Which of the following amino acid cannot undergo transamination? a) Lysine b) Alanine c) Aspartic acid d) Glutamic acid 5. The amino acid required for synthesis of heme is: a) Glutamine b) Glutamic acid c) Glycine d) Lysine 6. All of the following are synthesized from tyrosine, except: a) Melanin b) Serotonin c) Dopamine d) Epinephrine 7. The fate of ammonia in brain is: a) Conversion to urea b) Conversion to glutamate c) Conversion to aspartate d) Remains as such

Thanks Dr. Basema Jaff