MargiAnne Isaia, MD MPH

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Advanced Nutrition
Proteins 1
MargiAnne Isaia, MD MPH
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PROTEINS INTRODUCTORY CONCEPTS
Humans eat proteins, but need Amino
Acids Amino Acid composition of the protein
the most important characteristic from
nutritional point of view Protein structure may
influence its digestibility In proteins - there
are 20 AA with cognate tRNA - Selenocysteine
(amino acid coupled with Selenium) -
post-translational modification some amino acids
achieve their final structure after their
precursors have been incorporated into the
polypeptide (hydroxyproline, methylhistidine)
Proteins contain 16 Nitrogen Weight ratio of
protein/nitrogen 6.25
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• Functions of Dietary Proteins
• Provide essential (indispensable) Amino Acids
  for the synthesis of tissue proteins, enzymes,
  co-enzymes, neurotransmitters, transport
  proteins, porphyrins, creatine, phosphocreatine
  and creatinine, etc
• Provide nitrogen (N in amine group) for
  synthesis of non-essential Amino Acids, nucleic
  acids, proteoglycans, and other molecules
• Provide energy (ATP) for body activities from
  carbon skeleton
• (1 g 4 kcal)
• Provide Alanine and other Amino Acids for
  conversion to Glucose (Glycogen)
• (glucogenetic AA gluconeogenesis)

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• COMMON AMINO ACIDS IN THE BODY
• - Indispensable (essential)
• - body synthesis inadequate to meet needs
• - Isoleucine (Ile), Leucine (Leu), Lysine
  (Lys), Methionine (Met), Phenylalanine (Phe),
  Theronine (Thr), Tryptophan (Trp), Valine (Val)
• Histidine
• - Dispensable (non-essential)
• - can be synthesized by the body from carbon and
  nitrogen donors
• - Alanine (Ala), Aspartic Acid (Asp), Asparagine
  (Asn), Glutamic Acid (Glu), Serine (Ser),
  Histidine
• Conditionally indispensable
• - under most normal conditions the body can
  synthesize them
• - Arginine (Arg), Cysteine (Cys), Glutamine
  (Gln), Glycine (Gly), Proline (Pro), Tyrosine
  (Tyr)
• Histidine indispensable for infants

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Amino acids (AA) 20 -
building blocks
a) Physiological states prematurity
newborn b) Pathological states severe
catabolic states stress
Conditionally Indispensable AA Synthesized in
The mixture of indispensable and conditionally
indispensable supplied by food proteins at
adequate intakes of total Nitrogen will assure
that both the Nitrogen and specific amino acid
needs are met.
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ARGININE -CONDITIONALLY INDISPENSABLE AA
- growth
Especially important during
- pregnancy
- un-controlled diabetes
- dietary deficiency of even one of essential AA
- recovery from injury, surgery, infection
ARGININE
Nitric Oxide (NO)
- Helps blood vessels to open up
- Improves blood flow
Arginine - Food sources

• Peanuts, nuts (almond, pecan, walnuts,
  hazelnuts, Brazil nuts)
• beans soy, garbanzo, chick peas

- buckwheat, wheat germ, oats
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• ARGININE BLOOD VESSELS
• When Nitric Oxide (NO) formation occurs within
  the endothelial cells lining blood vessels, the
  product is called Endothelialderived nitric
  oxide (EDNO)
• Function of EDNO
• It is a potent vasodilator that plays a major
  role in regulating systemic and pulmonary
  vascular resistance
• It inhibits the adherence of circulating blood
  cells (platelets, leucocytes) to the endothelium
• It suppresses the proliferation of vascular
  smooth muscle cells

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ARGININE BLOOD VESSELS
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ESSENTIAL AMINO ACIDS Recommended daily amount
WHO Amino Acid mg / kg of body
weight Adults Isoleucine 120 mg/kg
Leucine 39 mg/kg Lysine 30
mg/kg Methionin ( Cysteine) 10.4 4.1 (total
15 mg/kg) Phenilalanine (Tyrosine) total 25
mg/kg Threonine 15 mg/kg Tryptophan 4
mg/kg Valine 26 mg /
kg Children gt3 years of age 10-20 higher
than adult levels Infants 150 higher than
for adults
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BODY PROTEIN RESERVES 70 Kg male 11 kg
protein Tissue distribution Form Skeletal
muscle 43 50 of total protein in the body
Skin 15 is in the following
forms Blood 15 - Collagen (25) Viscera
(liver, kidneys) 10 - Myosin and actin Rest
brain, lung, heart, etc. - Hemoglobin
In
malnutrition collagen 50 of total protein
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• PROTEINS
• Protein turnover
• The process by which all body proteins are
  continuously broken down and re-synthesized
• - Protein synthesis and degradation
• Amino acid oxidation
• Urea production
• Nitrogen excretion
• Protein turnover influenced by
• State of feeding post-absorptive, prandial,
  postprandial
• Fasting
• Quantity and composition of meal (or diet)

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EXCHANGE BETWEEN BODY PROTEIN AND AMINO ACID POOL
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PROTEIN TURNOVER AND INTAKE IN A HEALTHY 70-Kg
HUMAN
Protein intake 90 ( 70-100g)
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PROTEINS AND GENERAL METABOLISM Some tissues
more active - liver and intestine together
contribute as much as 50 of whole body protein
turnover. - skeletal muscle, the largest single
component of body protein mass (43 ),
contributes only about 25 to total body protein
turnover.
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Protein digestion Enzymes (site of
secretion) Pepsin (stomach) Enteropeptidase
(duoden) Trypsinogen (pancreas) Chymotrypsinogen
(pancreas) Procarboxypeptidase A
(pancreas) Procarboxypeptidase B
(pancreas) Proelastase (pancreas) Dipeptidases
(small intestine) Tripeptidases (small
intestine) Aminopeptidases (small intestine)
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• PROTEINS
• Absorption of Amino Acids
• The amino acid transporters are membrane bound
  proteins that recognize different Amino Acids
  and move them into and out of cells
• there are 2 types of transporters
• Sodium-independent
• Sodium-dependent

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PROTEIN ABSORPTION
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• PROTEIN
• Protein degradation or breakdown
• Important for
• Cell growth
• Adaptation to different physiological conditions
• Elimination of abnormal or damaged protein
• Normal functioning of the immune system

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PROTEIN - Breakdown Pathways Ubiquitin-proteaso
me pathway (in the cytoplasm) - energy
dependent (ATP) - digestion occurs in the
multisubunit 20 S proteasome, which in
association with a large 19 S regulatory
particle forms the 26 S complex - breaks
down abnormal proteins, normal proteins and
proteins of the endoplasmic reticulum -
activated by fasting
hormones (Glucagon, Glucocorticoids, Thyroxin)
- inhibited by feeding and increased
protein intake hormones (Insulin, Growth
Factors) Lysosomes - contain acidic enzymes -
breakdown extracellular proteins and surface
receptors Mitochondrial proteases - breakdown
mitochondrial proteins
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• PROTEINS Amino Acid Metabolism
• The amine (a-NH2 ) groups of amino acids
  involved in
• Transamination of the NH2 group to an organic
  keto-acid forming an amino acid (all tissues)
• Deamination (liver and kidneys)
• Formation of Urea (liver only)
• Conversion to ammonia (NH3) (kidneys)

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• PROTEINS Amino Acid Metabolism
• Transamination
• The 1st step in the catabolism of most Amino
  Acids involves the removal of the a-amino group
• Removal of the aamino group results in
  conversion of the Amino Acid to the corresponding
  Keto-Acid
• The conversion of Amino Acids to Keto-Acids is
  catalyzed by enzymes called Transaminases
• Transaminases use Vitamin B6 as cofactor
• Ex. Reaction Catalyzed by Alanine Transaminase
  (ALT)
• (Glutamate Pyruvate Transaminase, GPT)
• Alanine a-Ketoglutarate fg Pyruvate
  Glutamate
• ALT (GPT)
• Vitamin B6

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PROTEINS Amino Acids and their
corresponding Keto-acids Number of
Carbons Amino form Keto form (amino acids)
(keto-acids)
3 Alanine
Pyruvate 4 Aspartic acid
Oxalo-acetic acid 5
Glutamic acid
a-Ketoglutarate 6
Leucine
a-ketoisocaproic acid Pyruvate and
a-Ketoglutarate intermediates of Glucose
metabolism Used as energy sources (TCA cycle)
during periods of energy restriction
chronic starvation, protein-restricted diet
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PROTEINS AMINO ACID METABOLISM
Oxidative deamination Occurs in liver and
kidney Catalyzed by Glutamate Dehydrogenase (
GDH) Releases Ammonia, which may be converted to
Urea Example Glutamic Acid a-
Ketoglutarate Ammonia(NH4)
NAD GDH NADH
H Aspartate and Ammonia are the precursors
of Urea Body gets ride of excess of Nitrogen
(The Urea cycle)
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PROTEINS AND GENERAL METABOLISM
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AMINO ACIDS METABOLISM THE FUNNELING OF AA
THROUGH GLUTAMATE The enzyme
Glutamine Synthetase adds Ammonia to Glutamate to
produce Glutamine Glutamine is converted to
Glutamate and Ammonia by the enzyme Glutaminase
VALINE
ISOLEUCINE
LEUCINE
NH3 a-Ketoglutarate
GLUTAMATE
ALANINE
ASPARTATE
GLUTAMINE
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METHIONINE AND CYSTEINE More abundant in animal
and cereal proteins that in legumes CYSTEINE
- involved in neural modulation -
conditionally indispensable for premature infants
and individuals with cirrhosis TAURINE Sulfur
containing AA formed from Cys, not incorporated
into proteins Functions conjugation with bile
acids neural modulation
premature infants ( found in nerves and
muscles) Children on long-term TPN without
Taurine, retinal changes
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• GLUTAMINE
• - Nitrogen carrier shuttle
• - Metabolic intermediate
• - purine and pyrimidines synthesis
• - glucosamine synthesis
• Glutathione
• Tripeptide made of Glutamate, Glycine, Cysteine
• Free radical scavenger
• - Energy source
• Intestinal repair and function

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REFERENCES 1. Shils M et al, Modern Nutrition
in Health and Disease, 10th Edition 2. www.
Pubmed.org
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