Amino acids – importance (buffering

ability) and problems (cystinuria)

Learning course “Biochemistry I”
Fall semester, 2022
Eka Kldiashvili
 Amino acids – basic concepts
Amino acid (AA) consists
of a carbon atom
attached to a/an: 
Carboxyl group 
(-COOH)
Hydrogen atom
Amino group 
(-NH2)
Variable R group
(side chain):
determines unique
properties
Amino Acids and Proteins
Nagai, Ryoji, Medical Biochemistry, Chapter 2, 7-23
Structure of an amino acid. Except for glycine, four different groups are attached to the α-
carbon of an amino acid. Table 2.1 lists the structures of the R groups.
Copyright © 2019 © 2019, Elsevier Limited. All rights reserved.
Amino acids – basic concepts
• Only L-form amino
acids are incorporated
into proteins.
• There are 21
standard proteinogeni
c amino acids in
humans
20 are encoded
for protein synthesis by
the genetic code
Selenocysteine is
incorporated via a
mechanism known as
Amino Acids and Proteins translational recoding
Nagai, Ryoji, Medical Biochemistry, Chapter 2, 7-23
Enantiomers. The mirror-image pair of amino acids. Each amino acid represents
nonsuperimposable mirror images. The mirror-image stereoisomers are called
enantiomers. Only the l-enantiomers are found in proteins.
Copyright © 2019 © 2019, Elsevier Limited. All rights reserved.
 The net charge and polarity of AAs can change
according to the surrounding pH and
availability of H+ available for protonation. 

When charged, AAs become polar/hydrophilic.

Acid dissociation constant (pKa) 

 Indicates the strength of a weak acid or
base
 Defined as the pH at which the ionized
and unionized forms exist in equal
concentrations

All AAs have at least two ionizable groups, each

with its own acid dissociation constant (pKa).
pKa of the α-carboxyl group = 2
pKa of the α-amino group = 9–10
Acidic/basic AAs have another pKa for their
ionizable side chain group, which varies.
Amino Acids and Proteins
Nagai, Ryoji, Medical Biochemistry, Chapter 2, 7-23
Titration of amino acid. The curve shows the number of equivalents of NaOH
consumed by alanine while titrating the solution from pH 0 to pH 12. Alanine contains
two ionizable groups: an α-carboxyl group and an α-amino group.
Copyright © 2019 © 2019, Elsevier Limited. All rights reserved.
 The total  concentration
of amino acids in the
blood is ~3 mM.

Glutamine and alanine

are the largest
contributors, amounting
to about 35% of the
total.

With a weight-
maintaining, typical
Western diet, the total
concentration of amino
acids in the blood
changes by less than
~20%.
Digestion of Dietary Protein and Net Synthesis of Protein in the Body
Ronner, Peter, PhD, Netter's Essential Biochemistry, Chapter 34, 367-379
Concentration of individual amino acids in human blood plasma. (Data from Cynober LA.
Plasma amino acid levels with a note on membrane transport: characteristics, regulation,
and metabolic significance. Nutrition. 2002;18:761-766.
Copyright © 2018 Copyright © 2018 by Elsevier, Inc. All rights reserved.
 Clinical case
A 43-year-old man presents to the emergency department complaining of
nausea and severe right flank pain that started one hour ago.
The pain is intermittent, radiates to his groin, and has no associated
aggravating or alleviating factors.
He reports no previous similar episodes.
The patient denies chest pain, shortness of breath, vomiting, diarrhea,
constipation, changes in urination such as frequency and urgency, and visible
blood in the stool or urine.
He has no significant past medical history and takes no medications. His
family history is noncontributory. He does not smoke, drink, or use illicit
drugs.
The patient’s vital signs are: temperature 36.7 °C, heart rate 110 beats per
minute, respirations 14 per minute, and blood pressure 150/76 mm Hg.
The patient is diaphoretic and unable to sit still due to pain (rated 10 of 10 on
the pain scale).
His abdominal examination reveals active bowel sounds without tenderness
to percussion or palpation and no guarding or rebound tenderness.
No organomegaly or masses are palpable.
Tenderness is present at the right costovertebral angle. The remainder of the
physical examination is normal.

Given the severity of the pain, radiation to the groin, and costovertebral
angle tenderness, a stone in the urinary tract is high on the differential
diagnosis. 
• Cystine is the disulfide derivative of the
amino acid cysteine.
• Abnormal cystine transport can produce two
diseases: cystinuria and cystinosis. Both
disorders are inherited in an autosomal
recessive fashion.
• Abnormal cystine transport between cells
and the extracellular environment causes
cystinuria, one of the most common
inherited disorders of metabolism.
• Cystinuria is a genetically heterogeneous
disorder caused by a defect of dibasic amino
acid transport affecting the epithelial cells of
the gastrointestinal tract and renal tubules.
• As a result, cystine, lysine, arginine, and
ornithine are excreted in urine in quantities
higher than normal.
• Cystine is the most insoluble of the amino
acids; therefore elevated urinary cystine
predisposes to the formation of renal calculi
(kidney stones).
 Cystinuria
•Definition: an inherited genetic disorder
characterized by the accumulation
of cystine in the kidneys and bladder due
to a disruption of amino acid transporter
function in the proximal convoluted
tubule and intestine.  •Mechanism:
•Epidemiology: incidence is ∼ 1:7,000
•Inheritance: autosomal recessive
•Mechanism: impaired renal reabsorption
of dibasic amino acids (cystine, ornithine,
arginine, lysine) →accumulation of cystin
ein the urine → frequent formation of
hexagonal cystine stones
•Clinical
features: recurrent nephrolithiasis,
starting as early as childhood  involvement (e.g., hepatomegaly)
Cystinosis
•Definition: inherited genetic disorder
characterized by impaired cystine storage 
•Epidemiology: incidence of the most common
form (infantile cystinosis) is up to 1:200,000
•Inheritance: autosomal recessive
–Defective transport of cystine out
of lysosomes → accumulation
of cystine within lysosomes
–Three clinical forms in order of severity:
infantile > juvenile > ocular
(adult) cystinosis (The infantile form is the
most severe form.)
•Clinical features: Failure to thrive; Vomiting,
weakness, dehydration; Polyuria, polydipsia;
Progressive renal failure; Photophobia (due to
corneal crystal formation); Additional organ