essential amino acids in medicine, history, function of essential and non-essential amino acids, classification of proteins, properties and functions of proteins, metabolism of amino acid and proteins, disorders of amino acid deficiency, inborn errors of metabolism, recommended daily intake of essential amino acids

1. FOOD AS MEDICINE:
ESSENTIAL AMINO ACIDS
by
Kevin KF Ng, MD, PhD
Former Associate Professor of Medicine
Division of Clinical Pharmacology
University of Miami, FL., USA
Email: kevinng68@gmail.com
Presented at Health Care Providers Seminars 2018

2. Outline of Slide Presentation
▪ Definition of an essential amino acid.
▪ History of discovery of essential amino acids.
▪ Classification of essential amino acids.
▪ Properties and functions of essential and non-essential amino acids.
▪ Metabolism of amino acids: anabolism, catabolism, and amino acid pool.
▪ Proteins: classification, structures, functions, breakdown and half-lives.
▪ Disorders of amino deficiency and inborn errors of metabolism.
▪ General and specific laboratory tests for amino acid disorders.
▪ Recommended daily intake of essential amino acids.
▪ Summary.

3. What is the meaning of essential amino acid?
cannot be synthesized by the body
Essential
amino acids
(9)
must be obtained from dietary source
can be synthesized by the body
Non-essential
amino acids
(11)
not needed from dietary source
Amino acids

4. What are essential and non-essential amino acids?
▪ There are 9 essential amino acids and
11 non-essential amino acids used by humans.
▪ These 20 amino acids are linked in the molecules
of approximately 25,000 proteins in the body.
▪ A typical human protein is made of
220 amino acids.
▪ Each protein has a unique function in the body.

5. Timeline of Discovery of Essential Amino Acids

6. What is an amino acid?

7. Structure of 9 essential and 11 nonessential amino acids

8. Classification of amino acids
1. Based on chemical structure
2. Based on polarity of side chain
3. Based on Nutrition source
4. Based on metabolic fate

9. Nutritional classification of amino acids

10. Difference between essential and non-essential amino acids
▪ 20 amino acids are found in the human body.
▪ 9 are essential (indispensable) amino acids: histidine, isoleucine, leucine, lysine,
methionine, phenylalanine, threonine, tryptophan and valine.
▪ 11 are non-essential (dispensable) amino acids: Arginine, Glycine, Alanine, Serine,
Cysteine, Asparagine, Aspartate, Glutamine, Glutamate, Tyrosine and Proline.
▪ 21st amino acid Selenocysteine ?
▪ Essential amino acids cannot be synthesized in the body.
▪ Essential amino acids must come from food.
▪ Non-essential amino acids can be synthesized by the human body.

11. Biosynthesis of non-essential amino acids
▪ Non-essential amino acids are present in all meats.
▪ Some non-essential amino acids are synthesized from essential amino acids.
▪ Foods that do not contain all the amino acids are described as incomplete in
amino acid.
▪ Foods deficient in essential amino acids are known to lead to protein deficiency
disorders.
▪ Food combinations that provide all the amino acids may satisfy the dietary need.

12. Origin of essential and non-essential amino acids
https://bareblends.com.au/blog/the-9-essential-amino-acids-what-are-they-and-why-do-we-need-them/
Non-essential amino acid Source

13. Revised classification of nutritional amino acids
http://ib.bioninja.com.au/options/option-d-human-physiology/d1-human-nutrition/amino-acids.html

14. Sites where amino acids are used in the body
Amino acids are present in
every living cell of the body.
http://hompes-method.com/testing-toolkit/amino-acids-and-how-to-test-for-your-deficiencies-and-imbalances/

15. Major functions of essential amino acids
▪ Building blocks of protein ▪ Muscles, bone, skin, hair, nails
▪ Plasma and nuclear membranes
▪ Enzymes
▪ Hormones
▪ Precursors/substrates for vitamin, neurotransmitters, etc
Tryptophan ▪ Niacin, serotonin
Tyrosine ▪ Melanin, Thyroid stimulating hormone, Catecholamines
Glutamic acid ▪ GABA (gamma-aminobutyric acid)
Arginine ▪ Nitric oxide
Precursor for ▪ Heme, creatine, glutathione, porphyrin, purines and pyrimidines

16. Functions of non-essential amino acids
▪ Provide 55% - 60% of daily energy requirement
▪ Formation of structural elements: cartilage, bone and nervous tissue
▪ Can be synthesized from other biological sources in the liver
▪ Serve as building blocks of protein together with essential amino acids
▪ Conversion to glucose as energy source or fatty acids as excess calories

17. What is Metabolism of amino acids?
http://www.differencebetween.info/difference-between-metabolism-catabolism-and-anabolism

18. Distribution of protein in whole body, tissues and plasma
water
61%
protein
17%
fat
17%
carbohydrate
5%
albumin
54%
α1-globulin
8%
α2-globulin
8%
β-globulin
13%
¥-globulin
11%
fibrinogen
6%
muscle
50%
bone
20%
other
20%
skin
10%
Whole body Tissues Plasma proteins

19. Classification of Protein
▪ Size typical protein contains 200-300 amino acids.
Molecular weight range from 6,000 Daltons to millions of Daltons
▪ Shape Globular proteins are compact, soluble and spherical .
Fibrous proteins are elongated and insoluble.
▪ Structure Primary (correct sequence of amino acids)
Secondary (alpha helix, beta–pleated sheet)
Tertiary (three dimensional shape of the protein)
Quaternary (2 or more polypeptide chains binging together)
▪ Function
http://ib.bioninja.com.au/standard-level/topic-2-molecular-biology/24-proteins/protein-structure.html

20. Where are proteins found in the body?
▪ Proteins are found in all living cells.
▪ There are about 25,000 proteins in human body.
▪ A typical protein has about 220 amino acids
▪ Each protein has a unique function:
▪ structural component: muscle, bone, skin, hair,
cell and nuclear membrane
▪ digestion of food by gastrointestinal enzymes
▪ transport of oxygen by hemoglobin
▪ synthesis of immune antibodies
▪ synthesis of cytokines and chemokines
▪ function as neurotransmitters
▪ regulation of gene transcription
https://qbi.uq.edu.au/brain/brain-physiology/what-are-neurotransmitters

21. Properties of proteins
▪ Proteins are large molecules: e.g.
▪ Transport into cells require specific receptor mechanism
▪ Proteins vary in composition, size, function and half-lives.
▪ Half-lives vary between minutes (enzymes) to days or months (structure)
depending on their functions.

22. Properties and functions of 3,000 – 5,000 proteins within one cell
▪ different sizes: 200-300 amino acids.
▪ different molecular weights: thousands to
millions of Daltons.
▪different shapes: simple, conjugated.
3,000 – 5,000 proteins in 1 cell ▪different structures: primary, secondary, tertiary,
quaternary.
▪different functions: nutrition, acute phase proteins,
immune defense proteins, transport proteins,
hemostasis, etc.
▪different half-lives

23. Functions of proteins
▪ Anatomical structures Bones, skin, hair, nail, cell membrane
▪ Physiological functions Muscle movement with myosin, actin
▪ Biochemical functions Enzymes
▪ Endocrine function Hormones: autocrine, paracrine, endocrine
▪ Nervous system Neurotransmitters
▪ Immune system Antibodies
▪ Cellular communication Cytokines, chemokines, receptors
▪ DNA (deoxyribonucleic acid) Gene expression

24. What is Metabolism ?
https://speedymetabolism.com/metabolism-meaning/
Synthesis Breakdown/Degradation

25. Synthesis of Protein from Transcription to Translation
of mRNA to Protein
https://www.ck12.org/biology/translation/lesson/Translation-of-RNA-to-Protein-BIO/

26. Synthesis of a protein: Peptide bond between 2 amino acids

27. Breakdown of Proteins
process 10-20%
process 80-90%

28. Breakdown of exogenous protein by
proteolytic enzymes: proteolysis

29. Breakdown of protein to amino acids
from digestive system to circulating blood
http://www.mysportscience.com/single-post/2017/10/18/How-much-protein-do-I-need-to-eat-to-build-muscle
,Etc.

30. Breakdown of intracellular proteins by
lysosome
Discovered and named by Belgian biologist Christian de Duve, who eventually received the Nobel Prize in Physiology or Medicine in 1974

31. Breakdown of intracellular proteins by
ubiquitin-proteosome
https://www.semanticscholar.org/paper/Hijacking-of-the-Ubiquitin%2FProteasome-Pathway-by-t-Seissler-
Marquet/f6fdeab5faa3141b4d0ba262210e6662a7aa261a/figure/0

32. Protein turnover and half-life
▪ Protein turnover is the balance between
protein synthesis and protein degradation.
▪ More synthesis than degradation indicates
an anabolic state that builds lean tissues.
▪ More degradation than synthesis indicates a
catabolic state burns lean tissues.
▪ Protein turnover rates vary according to their
half-lives which range from minutes to years.
https://www.researchgate.net/publication/50214748

33. Turnover of proteins
https://www.docsity.com

34. Rate of protein turnover and half-lives of proteins
Rate of protein turnover
▪ Short-lived protein: minutes to hours
▪ Long lived proteins: days to months
▪ Structural proteins: months to years
T½ - lactic acid dehydrogenase
Tissue Half-life
▪Heart 16 days
▪Muscle 31 days
▪Liver 16 days

35. Metabolism of amino acids – General Aspects
▪ Generate energy
▪ Synthesis of glucose
▪ Formation of fat or ketone bodies
▪ Synthesis of non-essential amino acids
▪ All amino acids except lysine, threonine,
proline and hydroxyproline participate in
transamination.
http://www.biologydiscussion.com/metabolism/amino-acids-metabolism/metabolism-of-amino-acids-a-close-look-with-diagram/11273

36. Metabolism of Proteins and Amino Acids in the Body

37. Fate of endogenous and exogenous amino acids
▪ About 75% of the liberated amino acids are
reutilized.
▪ The remaining 25% are used as precursors
for other biological components.
▪ Excess amino acids are not stored but enter
the amphibolic pathway where they are
degraded into intermediates for the
synthesis of other products.

38. Disorders caused by Protein Deficiency
▪ Protein deficiency disease is rare in developed countries
▪ Deficiency mainly occur
• in under-developed and developing countries
• impoverished communities in developed countries
• malnutrition in elderly
• disorders of gastrointestinal digestion and absorption
▪ Genetic disorder in protein synthesis

39. Systems affected by deficiency of proteins
▪ Anatomical structures Bones, skin, hair, nail
▪ Physiological functions Muscle movement with myosin, actin
▪ Biochemical functions Enzymes
▪ Endocrine function Hormones: autocrine, paracrine, endocrine
▪ Nervous system Neurotransmitters
▪ Immune system Antibodies
▪ Cellular communication Cytokines, chemokines, receptors
▪ DNA (deoxyribonucleic acid) Gene expression

40. Which essential amino acid deficiency may cause
dysfunction in the body?
▪ Tyrosine deficiency leads to hypothyroidism.
▪ Tryptophan deficiency leads to depression.
▪ Cysteine deficiency leads to reduced level of
glutathione, an antioxidant.
▪ Lysine deficiency leads to retarded growth and
development.

41. Symptoms of amino acid deficiency
▪ Loss of muscle mass
▪ Low energy levels
▪ Depression
▪ Anxiety
▪ Memory and concentration problems
▪ Low thyroid function
▪ Allergic symptoms
▪ Digestive symptoms
▪ Increased body fat

42. Effects of loss of Proteins during starvation
http://www.tankonyvtar.hu/hu/tartalom/tamop412A/2011-0095_fogaszat_angol/ch01s32.htmlDistribution of protein, fat and carbohydrate in whole body

43. Protein Deficiency Disease
▪ Kwashiorkor: severe deficiency of protein deficiency
in diets containing mostly carbohydrates. Abdominal
swelling results from retention of fluids.
▪ Marasmus: severe deficiency of protein and calories
resulting in weight loss and dehydration. Marasmus
can result in starvation and death from lack of essential nutrients.
▪ Cachexia: a condition that results from protein deficiency,
depletion of skeletal muscle and an increased rate of
protein degradation.
▪ Abnormal bleeding due to deficiency of Protein C and Protein S
https://www.livestrong.com/article/269901-a-list-of-protein-deficiency-diseases/

44. Discovery of hereditary aminoacidopathies
(Inborn errors of amino-acid metabolism)
https://academic.oup.com/bmb/article-
abstract/25/1/35/270308?redirectedFrom=PDF
Cause: lack of specific enzymes
e.g. phenylketonuria (PKU)

45. Amino acid inborne error of metabolism: Phenylketonuria (PKU)
http://flipper.diff.org/app/items/info/611

46. Major Inborn errors of amino acid metabolism
http://www.biologydiscussion.com/metabolism/amino-acids-metabolism/metabolism-of-amino-acids-a-close-look-with-diagram/11273

47. General and specific laboratory tests for amino acid deficiency
and inborn error of metabolism
▪ Complete blood count with differential
▪ Urinalysis
▪ Blood gases
▪ Serum electrolytes
▪ Thyroid unction tests
▪ Blood glucose
▪ Plasma ammonia
▪ Plasma lactate
▪ plasma and urine amino acids, quantitative
▪ Urine reducing substances
▪ Urine ketones
▪ Urine organic acids

48. How much protein is needed daily?
▪ Different opinions exist on how much protein is needed daily.
▪ Most official nutrition organization recommend a modest
protein intake.
▪ The Dietary Reference Intake (DRI) is 0.8 grams of protein per
kilogram of body weight or 0.36 grams per pound.

49. 0
1
2
3
4
5
6
7
8
9
10
gperday
essential amino acids
Institute of Medicine recommended protein intake
(total 54 g) for amino acids in a 160 lb man

50. Recommended daily intake of essential amino acids for an adult
human by WHO and United States
https://en.wikipedia.org/wiki/Essential_amino_acid
12,880 mg184 mg/kg 214 mg/kg
+14%

51. Recommended daily intake of amino acids based on Total protein intake
▪ The Institute of Medicine lists its recommended daily intakes of amino acids as
percentages of your total protein intake. To determine how much protein should be
eaten, multiply the body weight by 0.8 grams.
▪ If you weigh 160 pounds, you need about 128 grams of protein per day.
160 x 0.8 g/lb = 128 grams
▪ Increasing your daily protein intake to more than 1 gram per pound of your body
weight does not benefit you, according to the University of California at Los Angeles
publication "Bulking Up,“
▪ Excess protein intake is not stored in the body, but broken down as ammonia and
urea or converted to glucose or fat.
http://healthyeating.sfgate.com/recommended-levels-essential-amino-acids-3649.html

52. Major Sources of Vegetable & Animal Proteins
https://www.pinterest.com/pin/553590979173177778/

53. List of essential amino acids in foods

54. List of Foods that Contain the Most Amino Acids
https://www.livestrong.com/article/267249-amino-acid-supplements-for-women/

55. Summary
▪ Of 20 amino acids used by humans, 9 are essential and 11 are nonessential.
▪ Essential amino acids cannot be synthesized by the body and must be ingested from
dietary source.
▪ Both essential and nonessential amino acids are building blocks of proteins.
▪ Proteins provide structural components from cells to tissues, organs and systems.
▪ Proteins are incorporated into receptors, enzymes, hormones, neurotransmitters, etc.
▪ Proteins are degraded into amino acids by exogenous and intracellular enzymes.
▪ The liberated amino acids are reutilized for protein synthesis or used as energy source.
▪ Protein or amino acid deficiencies are rare in developed countries.
▪ Inborn errors of metabolism are due to dysfunction of production, regulation, or function
of enzymes or enzyme co-factors.

56. ANY QUESTION?
Contact
Kevin KF Ng, MD, PhD
Email: kevinng68@gmail.com