AMINO ACIDS: Structure

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AMINO ACIDS Structure

• Proteins are a sequence of amino acids.
• Dietary protein is the main source of amino
  acids.
• Amino acids can be used as fuel, but usually
  more important roles for them are as building
  blocks for proteins, and as a source of carbon
  and nitrogen for biosynthesis of other
  biochemicals.

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• In the process of digestion, proteins are broken
  down to free amino acids in the gastrointestinal
  tract.
• They are then absorbed and pass into the
  circulation, and are transported to liver.
• Where -NH2 groups are removed by transamination.
• The resulting alpha-keto acid is then used as
  fuel, or as a biosynthetic intermediate.

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• Amino acids are not stored in the body like fats
  or carbohydrate
• Of course, amino acids are ubiquitous, being
  present in structural proteins, enzymes,
  transport proteins, etc.
• Some of these proteins (notably serum albumin)
  can be degraded under conditions of fasting or
  starvation, to release free amino acids.

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Amino acids

• The 20 amino acids are required for the synthesis
  of variety of protein besides other biological
  functions.
• In which 10 are essential amino acids, and 10
  are non-essential.
• Essential amino acids
• Which are essential to the body but cant be
  synthesized by the body.
• They are required for proper growth and
  maintenance of the body.

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• Non essential amino acids-
• The body can synthesized about 10 amino acids
  which are considered as NEA.
• There are also 2 amino acids namely arginine and
  histidine , can be partially synthesized by the
  adult human being ,so considered as semi
  essential amino acids.

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AMINO ACIDS Structure

• The side group creates unique characteristics for
  each amino acid so they differ in
• shape,
• size,
• composition,
• electrical charge,
• and pH.

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DIGESTION

• No digestion of protein takes place in the mouth,
  it begins in the stomach.
• Hydrochloric acid denatures protein and also
  converts pepsinogen to pepsin.
• Pepsin breaks the protein down into peptides of
  various lengths and some amino acids.
• Pepsin completes 10-20 of digestion

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DIGESTION

• Pancreas makes trypsinogen and chymotrypsinogen
  in the small intestine.
• These break down polypeptides into smaller
  peptides.
• Peptidases , continue to split the remaining
  polypeptides into tripeptides, dipeptides, and
  some amino acids

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• The cells of the small intestine absorb amino
  acids and some larger peptides, and release them
  into the bloodstream for use by the bodys cells
• Some amino acids share the same transport system,
  so if take in a large amount of one particular
  amino acid, it may be inhibiting the absorption
  of others.

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ABSORPTION

• gt99 amino acids are absorbed into the
  bloodstream.
• but some remain in the enterocytes and are used
  to synthesize enzymes and new cells.

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The roles of proteins in the body

• Support growth and maintenance
• Build enzymes, hormones, and other compounds
• Build antibodies
• Maintain fluid and electrolyte balance
• Maintain acid-base balance
• Clot blood
• Provide energy and glucose

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NITROGEN EXCRETION

• Amino acid breakdown yields an amino group
  (containing nitrogen)
• This molecule is unstable and is converted to
  ammonia
• Ammonia is toxic, so it is excreted from the
  cells and sent to the liver, where it is
  converted to urea and water
• The urea is transported to the kidney, where it
  is filtered from the blood and finally sent to
  the bladder for excretion in the urine .

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Disorders of urea cycle

• Hyperammonemia-
• Deficiency of any enzyme of urea cycle.
• When block is in one of the earlier steps
  condition is more severe since ammonia itself
  accumulates.
• Brain is very sensitive to ammonia,causes mental
  retardation.
• Deficiency of later stage enzyme results in the
  accumulation of other intermediates, which are
  less toxic.

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• Aminoaciduria -
• Rare inherited disorders of amino acid
  metabolism.
• Abnormality exist , either in the activity of a
  specific enzyme in metabolic pathway .
• Or in the membrane transport system.
• More than 100 disease have been identified that
  result from inborn errors of amino acid
  metabolism.

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• Because , filtered load of amino acids is
  increased.
• hence there is an increase in both, the
  amounts reabsorbed and those excreted.
• Secondary or 'overflow' aminoaciduria can also be
  seen in conditions in which there is hyper amino
  acidaemia.

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• Symptoms
• Usually appear in childhood and may include
• Diarrhea
• Mood changes
• Nervous system (neurologic) problems, such as
  abnormal muscle tone
• Red, scaly skin rash, usually when skin is
  exposed to sunlight
• Sensitivity to light (photosensitivity)

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aminoacidurias

• Phenyl ketonuria (type-1 and 2) - phenyl
  alanine hyroxylase
• Type- 4
  dihydropterin deficiency
• Tyrosinemia (type-2 ) - tyrosine
  transaminase
• Neonatel tyrosinemia - p-hydroxyphenylpyruvare
  dioxygenate
• Alkaptonuria -
  homogentisate oxidase
• Tyrosinemia (type-1 ) fumaryl acetoacetate
  hyrolase

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• Albinism - Tyrosinase
• Homo cystinuria (type-1) - cystathionine beta
  synthase
• Type - 2 - methylene
  THFA reductase
• Type 3 - methyl
  transferase
• Cystathionuria -
  cystathionase
• Histidinemia -
  histidase
• Glycinuria defect in
  renal absorption
• Hartnups disease defective
  intestinal absorption
• Maple syrup urine disease - branched chain keto
  acid
• 
  decarboxylase
• Methyl malonic aciduria - methyl malonyl CoA
  mutase

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Degradation Pathway of phenylalanine

• Enzymes Used
• Phenylalanine Hydroxylase (PKU)
• Aminotransferase - ( tyro-2)
• p-hydroxyphenylpyruvate - (neonatel tyro)
• 4. Homogenistate dioxygenase (alkaptonuria)
• 5. Maleylacetoacetate isomerase - tyrosinosis/
• 6. Fumaryl aceto acetate
  (tyro-1)

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WHAT IS PKU?

• PKU (phenylketonuria), is a rare, inherited
  metabolic disease that results in mental
  retardation and other neurological problems when
  treatment is not started within the first few
  weeks of life. .

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Phenylketonuria

• Cause
• Phenylalanine hydroxylase deficiency
  (classical)
• Dihydropiopetrin reductase deficiency
  (atypical)
• Acccumulation of
• Phenylalanine
• phenylpyruvic
• phenyllactic
• phenylacetic

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• Symptoms of PKU -
• Mousy odour of urine
• Mental retardation
• Neurological manifestations
• hypopigmentation
• Diagnosis
• Phenylalanine level in blood the 4Th day of
  birth
• Treatment
• Diet with very low amount of phenylalanine

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DIAGNOSIS

• Screening
• Guthrie Test, Blood phenylalanine,
• Urine ferric chloride test
• High Phenylalanine gt 20 mg/dl.
• High Phenyl pyruvic acid.

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Hyper tyrosinemias

• Tyrosinemia type 2-
• It is due to deficiency of enzyme tyrosine
  transaminase.
• Accumulation and excretion of tyrosine and its
  metabolites, p-hydroxy phenyl pyruvate, phydroxy
  phenyl lactate, p hydroxy phenyl acetate .
• Symptoms are-
• Skin dermatitis, eye lesions, disturbed self
  coordination is also seen .

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Neonatal tyrosinemia

• Absence of enzyme p- hydroxyphenyl pyruvate
  dioxygenase.
• Mostly a temporary condition and usually reespond
  to ascorbic acid.

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Alkaptonuria

• Alkaptonuria is an autosomal recessive condition.
• Metabolic defect is the deficiency of
  homogentisate oxidase.
• Results in excretion of homogentisic acid in
  urine.
• Homogentisic acid on standing is oxidized by
  polyphenol oxidase to benzoquinone acetate.
• Which give black or brown colour.

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• Symptoms-
• Polymerization reaction produce a pigment called
  alkapton.
• Its deposition occurs in connective tissues,
  bones and various organs, resulting a condition
  Ochronosis.
• Patient suffer from arthritis because of this
  depostion of this pigment.
• Diagnosis- change in colour of the urine on
  standing to brown or black
• Treatment- low phenylalanine diet consumption

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Tyrosinemia type-1 /tyrosinosis

• Deficiency of enzyme fumarylacetoacetate
  hydroxylase or maleylacetoacetate isomerase.
• Rare but serious disorder
• Causes liver failure, rickets, renal tubular
  dysfunction and polyneuropathy.
• In acute stage, infants exhibits, diarrohea,
  vomiting.
• Death may even occur due to liver failure.

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Albinism

• Inborn error, due to lack of synthesis of the
  pigment melanin.
• May be due to deficiency or lack of enzyme
  tyrosinase or presence of inhibitors of
  tyrosinase.
• Clinical manifestations-
• Most imp work of melanin is the protection of
  body from sun radiation.
• Lack of melanin in albinos makes them sensitive
  to sunlight.
• Suseptible to skin cancer, photophobia (
  intolerance to light)

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Hypopigmentation

• Vitiligo and leukoderma are the localized hypo
  pigmentation disorders.
• Vitiligo is an acquired progressive disease with
  loss of melanin around mouth, nose eyes .
• Leukoderma usually starts with hands and than
  spred.

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Hartnups Disease

• Hartnup disorder is an inherited metabolic
• condition that involves the transport of certain
• amino acids like tryptophan and histidine, in
  the
• small intestine and kidneys
• Under normal circumstances, the renal tubules
  reabsorb in excess of 93 of the amino acids
  filtered from the plasma

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Hartnups disease

• Tryptophan and other neutral amino acids are not
  absorbed in the small intestine and are converted
  by gut bacteria into indolic compounds .
• Tryptophan absorption is most severely affected ?
  Symptoms of pellagra are observed in the
  patients.
• These compounds are toxic to the CNS.
• Causes -
• A child must inherit the defective gene from both
  parents in order to be seriously affected.
• Hartnup disorder affects both renal and
  intestinal uptake of neutral amino acids.

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Inborn errors of suplhur amino acids

• Cystinuria-
• Most common inherited disease.
• In this disease, carrier system in renal
  tubules become defective leading to the
  excretion of four amino acids, Cysteine, lysine,
  ornithine and arginine
• Cysteine is insoluble and increased conc.
  leads to the formation of cystine stones in
  kidney and urinary tract.

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• Homocystinuria type-1
• METHIONINE Cystathionine
• Defect in the enzyme Cystathionine synthase.
• Accumulation of homocysteine result in various
  complications, like thrombosis, osteoporosis and
  ofenly mental retardation.
• Also associated with the damage to endothelial
  cells which might lead to atherosclerosis.

Cysathionine
ß Synthatase
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• DIAGNOSIS
• HIGH METHIONINE AND HOMOCYSTINE.
• TREATMENT
• High dose of B6 and Folic Acid.
• Low methionine and high cystine diet,
• Betain (trimethylglycine)

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MSUD (Maple syrup Urine Disease)

• Metabolic disorder of branched chain amino acids.
• It is due to a defect in the enzyme branched
  chain a keto acid dehydrogenase which convert
  a keto acids to respective acyl Co A thioesters.
• Hence, plasma and urine conc of brabched chain
  amino acid and their keto acid is high .
• Known as branched chain ketonuria.
• The urine of affected person smells like maple
  syrup or brunt sugar.

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• Biochemical complications-
• Reduced protein biosynthesis.
• Branched chain amino acids competitively inhibit
  glutamate GDH .
• The disease result in acidosis, lethargy,
  convulsions, mental retardation, coma and finally
  death within one year after birth.
• Diagnosis-
• Estimation of urine for B C amino acids.
• Treatment-
• feed diet with low content of BC amino acids.