Metabolism of Amino Acids

A. Metabolism: Proteins, Amino Acids

Glucogenic Glucogenic & Ketogenic Ketogenic
(Nonessential)
Alanine tyrosine
Asparagine
Aspartate
Cysteine
Glutamate
Glutamine
Glycine
Proline
Serine
(Essential)
Arginine Isoleucine Leucine
Histidine Phenylalanine Lysine
Methionine Tryptophan
Threonine
Valine

A. Classification of amino acid as exclusively glucogenic, glucogenic

and ketogenic, or exclusively ketogenic
 B.
Tryptophan

Histidine Arginine Leucine

Valine

Phenylalanine PVT TIM HALL Lysine

Threonine Methionine

Isoleucine

Fig. 1
B. Some students may find “PVT TIM HALL” helpful in recalling the
essential AA.
Functions of Proteins

1. Enzymatic catalysis
2. Transport and storage
3. Coordinated motion
– responsible for movements in the body (muscles)
4. Mechanical support
– support of body - bones and muscles
5. Generation and transmission of impulses
6. Control of growth and differentiation
AA - simplest form of proteins
20 AA
Characteristics of proteins

1. Have more members

2. Fundamental component of protoplasm
3. Elements in protein
C, H, O, N (I & Fe)
4. Proteins are considered macromolecules,
composed of a number of AA joined together by
peptide bond or linkage
5. Only foodstuff when absent in the diet will cause
death
6. Utilize in the body for growth
Digestion of Proteins

1. Mouth - food is chewed

2. Stomach:
Gastrin - triggers chief cells to release Hcl and
pepsinogen
3. Small intestines:
– Secretin-stim. release of pancreatic juices
– Activation of proteolytic enzymes:
Trypsinogen → trypsin
Chymotrypsinogen → chymotrypsin
Proelastase → elastase
Endo & exopeptidases → activated
Products of enz action = amino acids
Dipeptides & small peptides → AA
Greater amount of AA in portal blood is in the form
of alanine
STOMACH

• Protein digestion starts in the stomach

• dietary proteins become denatured by gastric acid
→ important for protein digestion because proteins
are poor substrates for proteases

ACID ENVIRONMENT is required for action of pepsin

PEPSIN

• A protease that works optimally at pH 2

• a carboxyl protease
• acts mostly as endopeptidase
• does not cleave at random
• prefers peptide bonds formed by amino group of
aromatic AA
• major breakdown products are not free AA but a
mixture of oligopeptides known as peptones
INTESTINE

As acidic stomach contents reach duodenum →

rapidly neutralized by HCO3 in pancreatic
secretions.

Proteolytic enzymes from pancreas include:

1. Trypsin
– a serine protease
– endopeptidase
– specific for “CO” side of basic AA
2. Chymotrypsin
– a serine protease
– endopeptidase
– specific for “CO” side of hydrophobic AA
1 & 2 = degrade peptones to smaller peptides

3. Carboxypeptidase A:
– hydrophobic AA at “C” terminal

4. Carboxypeptidase B
– basic AA at “C” terminus
PROTEIN TURNOVER

• A continuous process of protein degradation into

AA and re-synthesis of proteins for AA’s
• 1-2% of total body protein/day: primarily for
degradation of muscle proteins
RDA = 30 60 gm proteins/day

PROTEIN QUALITY:
– Proportion of essential AA in food relative to
their proportion in proteins being synthesized
• excess AA are not stored
• those not incorporated into new proteins are rapidly
degraded
• unlike CHO’s and lipids, proteins and AA are not
stored by the body
• proteins are present in all cells
• some of the body’s proteins can be mobilized
during fasting or starvation → “C” skeletons of AA’s
are burned for energy or converted to glycogen or
TG → stored.
“Amino acid pool”:
• is not a storage place for AA’s
• is a convenient way to indicate that small amounts
of AA’s are present in cells or circulate in blood
During starvation:
• much of plasma proteins (esp albumin) are utilized
first
• rapidly metabolizing tissues (liver, pancr, intesti
mucosa) - tend to lose their proteins quickly
• muscle is slow to yield AA’s
MAJOR PATHWAYS FOR DEGRADATION OF
INTRACELLULAR PROTEINS

1. Lysosomal
• membrane-associated proteins
• long-lived intracellular proteins
• cathepsins
2. Cytosolic
• require ubiquitin, ATP
• for abnormal and short-lived proteins
WHAT FACTORS TARGET A PROTEIN FOR
DEGRADATION?

• For proteins in circulation:

– loss of sialic acid moiety from non-reducing ends
of oligosaccharide chains → signal degradation
asialated glycroproteins → recognized by
receptors in liver cells → internalized →
degraded in lysosomes by cathepsins
THE 20 AMINO ACIDS USED FOR BUILDING
PROTEIN CHAINS:
Aliphatic nonpolar side chains:
gly leu val
ala ile

Aromatic side chains:

phe tyr trp

Hydroxyl-containing side chains:

ser thr
Acidic side chains:
asp (d) glu (e)

Amidic amino acids:

asn (n) gln (q)

Basic side chains:

lys arg his

Sulfur-containing side chains:

cys met

Imino acid: pro

 Common AA’s = those AA’s for which at least one
specific codon exists in the genetic code

Derived AA’s = in proteins are formed from one of

the common AA’s after the common AA has been
incorporated into protein structure

Aromatic AA’s:
Phe contains benzene ring
Tyr contains phenol grp
Trp = R grp contains a heterocyclic structure -
indole nucleus
* In all 3 AA’s → the aromatic moiety is attached to
the a-c thru a methylene (-CH2)
 SOME HUMAN GENETIC DISORDERS AFFECTING
AMINO ACID METABOLISM
Name
• Albinism
• Alkaptonuria
• Argininosuccinic acidemia
• Homocystinuria
• Maple syrup urine disease
• Phenylketonuria
• Hypervalinemia
• Cytinosis
• Cystinuria
• Hartnup’s disease
• Histidinemia
• Isovaleric acidemia
Defective Enzyme or Process
• Tyrosine 3-monooxygenase
• Homogentisate 1,2-dioxygenase
• Argininosuccinate lyase
• Cystathionine β -synthase
• Branched-chain-α -ketoacid
dehydrogenase
• Phenylalanine 4-mono oxygenase
• Valine transaminase
• Storage and/ore release of cystine from
lysosomes
• Renal and intestinal transport of cysteine
• Renal transport of neutral AA
• Histidine ammonia lyase
• Isovaleryl CoA dehydrogenation
METABOLIC DISORDERS INVOLVING THE UREA
CYCLE

Disorders Enzyme Defect

Hyperammonemia-Type I Carbamoyl phosphate synthetase
Hyperammonemia-Type II Ornithine transcarbamylase
Citrullinemia Arginosuccinate synthetase
Arginosuccinic aciduria Arginosuccinase
Hyper argininemia arginase
CONVERSION OF AMINO ACIDS TO SPECIALIZED
PRODUCTS
1. Glycine
a. A-carbon & N atom → used for synthesis of
porphyrin moiety of Hb

b. Entire gly mol → forms position 4,5,7 of purine

skeleton

c. gly + cholic acid → glycocholic acid (bile acids)

d. gly + sam → sarcosine (n-methyl-gly)

component of creatine
2. Alanine
• Ala + gly → amino N2 in human plasma
∀ β-ala + his → present in carnosine
(major % in humans) (skel musc dipeptide)

3. Arginine - formamidine donor for creatine synthesis

in primates

4. Ornithine
a. plays a role in urea biosynthesis
b. precursor or mammalian polyamines spermidine
& spermine
5. Tryptophan
• precursor of serotonin
CO2
5 HT 5 hydroxytryptamine
(serotonin)

oxid deamination
Serotonin 5 hydroxyindole-acetate
mondamine oxidase
6. Tyrosine
• precursor of epinephrine & norepinephrine
• precursor of thyroid hormones - triiodothyronine
(T3) & thyroxine (T4)

7. Creatine & Creatinine

Creatine - present in muscle, brain, blood as
phosphocreatine free creatine
– n’ly present in urine (traces)
– synthesis involves 3 AA’s gly, arg, met
8. Gaba - γ-aminobutyrate
• formed fr glutamate by decarboxylation
• catabolism involves transamination → succinate
semi-aldehyde → succinate
SUMMARY OF THE BIOSYNTHESIS OF SOME
BIOGENIC AMINES

Amine Amino Acid Distinguishing Features of

Precursor Pathways
Acetylcholine Ser, met Sam is methylating agent
Norepinephrine Tyr L-dopa is intermediate & precursor of
melanins
Epinephrine Tyr, met Sam-dependent transaminase
activated by glucocorticoids
Serotonin Trp 5-hydroxy trp is intermediate (5-HT)
Gaba Glu Decarboxylation reaction
Histamine His Decarboxylation reaction
Spermine Ornithine met Spermidine is intermediate
Creatine Arg, gly, met Guanidino grp transferred to gly
GLUCOGENIC AND KETOGENIC AMINO ACID
Glucogenic alanine Ketogenic leucine
arginine lysine
asparazine tryptophan
aspartic acid
cysteine
glutamic acid Ketogenic and glycogenic
glutamine phenylalanine
glycine tyrosine
histidine
methionine
proline
serine
threonine
tryptophan
valine
ESSENTIAL AND NONESSENTIAL AMINO ACIDS
Essential Nonessential

Methionine Glutamate
Arginine Glutamine
Phenylalanine Proline
Threonine Aspartate
Valine Asparagine
Tryptophan Alanine
Histidine Glycine
Isoleucine Serine
Leucine Tyrosine
Lysine Cysteine