6.

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Amino Acid Metabolism II LE 6

AGNES ALARILLA-ALBA, MD 04/26/2018

OUTLINE Fate of Carbon Skeleton of Amino Acids

I. Catabolism of the Carbon Skeleton of Amino Acids ● Amino acids are catabolized to intermediates for carbohydrate
II. Amphibolic Intermediates Formed From Carbon and lipid biosynthesis
Skeletons of Amino Acids ● All then end up as part of:
A. Amino Acids That Form Oxaloacetate → Ketogenic amino acids
B. Amino Acids Related Through -ketoglutarate ▪ Produce ketone bodies
C. Amino Acids That Form Pyruvate ▪ Degraded to acetyl CoA or acetoaceyl CoA
D. Additional Amino Acids That Form Acetyl-CoA → Glucogenic amino acids
E. Branched-Chain Amino Acids ▪ Degraded to TCA intermediates
III. Conversion of Amino Acids to Special Products ▪ They can be then used for glucose synthesis
A. L- Amino Acids ● The entire or a portion of the carbon skeleton of every amino
acid is convertible to either:
B. Non- Amino Acids
→ carbohydrate
IV. Cases
→ fat
A. Phenylketonuria
→ both fat and carbohydrate
B. Maple Syrup Urine Disease
● Amino acids destined for energy metabolism must be
C. Albinism
deaminated to yield the carbon skeleton
D. Alkaptonuria
V. Conclusions

LEARNING OBJECTIVES
• To determine the principal catabolites of the carbon skeleton
• To predict the major metabolic fates of these catabolites
• To discuss the aminotransferase reaction and the role played by
the coenzymes
• To predict aminoacidurias
• Provide a common template of the clinical manifestations of
patients with aminoacidurias

I. CATABOLISM OF THE CARBON SKELETON OF

AMINO ACIDS

Overview
 The assembly of new proteins requires a source of amino
acids. These building blocks are generated by the digestion of
proteins in the intestine and the degradation of proteins within
the cell.
 Many cellular proteins are constantly degraded and
resynthesized. To facilitate this recycling, a complex system for
the controlled turnover of proteins is required
 The amino acids produced may be used in two ways.
1. They may be used to synthesize again another set of
protein.
2. Amino acids can be completely broken to give energy
Figure 2. Fate of Molecules in Amino Acids
and waste products (in the absence of carbohydrates)
Table 1. Classification of Amino Acids (memorize!)
GLUCOGENIC
GLUCOGENIC KETOGENIC
AND KETOGENIC
(13 AAs) (2 AAs)
(5 AAs)

Alanine Tyrosine
Asparagine
Aspartate
Cysteine
NON-
ESSENTIAL
Glutamate
Glutamine
Glycine
Proline
Serine

Arginine Isoleucine Leucine

Histidine Phenylalanine Lysine
ESSENTIAL
Methionine Tryptophan
Valine Threonine
Figure 1. Amino Acid Metabolism

Trans # 5 Group #25: Bañas, Datingaling, Dela Cruz, A., Dela Cruz, E. EDITOR: Chan 1 of 12
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● Tumor cells, especially leukemic cells, require asparagine for
Removal of Amino Groups growth
● Three mechanisms for removal of amino groups from amino → Asparaginase is given to convert asparagine to aspartate;
acids thus, decreasing the amount of asparagine available for
→ Transamination tumor growth
▪ Initiates amino acid catabolism ● Depletion of aspartate will inhibit RNA and DNA synthesis of the
▪ Removal of  amino nitrogen by transamination tumor
▪ Catalyzed by an aminotransferase
− The first catabolic reaction of all amino acids EXCEPT
proline, hydroxyproline, threonine, lysine
▪ The hydrocarbon skeleton that is left after the reaction is
degraded to amphibolic intermediates

Figure 3. Transamination Figure 5. Catabolism of Asparagine and Aspartate

→ Oxidative deamination
▪ Oxidative removal of the amino group resulting in keto B. Amino Acids Related Through -Ketoglutarate
acids and ammonia
→ Removal of a molecule of water by dehydratase
▪ Catalyzed by dehydratase

II. AMPHIBOLIC INTERMEDIATES FORMED FROM CARBON

SKELETONS OF AMINO ACIDS

Figure 6. Summary of Amino Acids Related to -Ketoglutarate

Glutamate and Glutamine

● Enzymes: glutaminase and transaminase
● No known metabolic effect
● Glutamate is an important component of GABA (remember)
→ GABA is associated with Parkinson’s Disease

Figure 4. Intermediates of Amino Acids in TCA

A. Amino Acids that Form Oxaloacetate

Asparagine and Aspartate

● All 4 carbons of asparagine and aspartate form oxaloacetate
via reactions catalyzed by asparaginase and a transaminase
● Metabolic defects in TRANSAMINASES are incompatible with
life Figure 7. Catabolism of Glutamine and Glutamate

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Proline  Initial reaction: conversion of arginine to ornithine →
transamination of ornithine → formation of glutamate-ɣ
semialdehyde → conversion to -ketoglutarate
● Arginase: catalyzes the cleavage of L-arginine to form urea and
L-ornithine
● Mutations of ornithine aminotransferase
→ Elevate plasma and urine ornithine
→ Associated with gyrate atrophy of the choroid plexus and
retina; because of this, brain defects occur
→ Treatment: restriction of dietary arginine
● Hyperornithinemia-hyperammonemia syndrome
→ A defective mitochondrial ornithine-citrulline antiporter
→ Ornithine cannot be transported into the mitochondria;
subsequently, it cannot act as intermediate in urea synthesis

Histidine
● Requires urocanate, 4-imidazolone-5-proprionate and N-
formiminoglutamate (FIGLU)
● Formimino group transfers to tetrahydrofolate → formation of
glutamate → formation of -ketoglutarate
● Practical application
→ Detection of folic acid deficiency: if FIGLU is excreted after
a high dose of histidine
→ Impaired hitidase: histidinemia and urocanic aciduria (benign
disorders)

Figure 8. Catabolism of Proline

● Catabolized in the mitochondria

● Does not participate in transamination
→ The nitrogen is retained throughout the oxidation to Δ-
pyrolline 5 carboxylate ring
● Metabolic disorders

→ Autosomal recessive that are consistent with normal life

→ Block at proline dehydrogenase: type 1 hyperprolinemia
→ Block at glutamate ɣ semialdehyde dehydrogenase: type 2
hyperprolinemia
▪ The dehydrogenase also participates in the catabolism of
arginine, ornithine, and hydroxyproline
▪ Since proline and hydroxyproline are affected, both Δ-
pyrroline-5-carboxylate and Δ-pyrroline-3-hydroxy-5-
carboxylate are excreted

Arginine

Figure 9. Catabolism of Arginine

Figure 10. Catabolism of Histidine
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Cystine and Cysteine
C. Amino Acids that Form Pyruvate or CO2 ● Cystine first reduced to cysteine by cysteine reductase
→ Related with renal stones
Glycine ● Cystinuria – a defect in renal reabsorption of cystine, lysine,
● Glycine cleavage complex of liver mitochondria splits glycine to arginine and ornitithine
CO2 and NH4 and forms N5,N10-methylene tetrahydrofolate ● May lead to cysteine calculi
● Consists of 3 enzymes and an H protein that is covalently ● Serine can also be converted to cysteine
attached dihyrolipoyl moiety
1. glycine-5-dehydrogenase (decarboxylating)
2. ammonia-forming aminotransferase
3. dihydrolipoamide dehydrogenase
● Produces non ketotic hyperglycemia
● Defect in hyperoxaluria is a failure to catabolize glyoxalate to
oxalate results in nephrolithiasis, nephrocalcinosis and renal
hypertension and dialysis
● Glycinuria is due to defect in renal tubular absorption → renal
stones

Figure 11. Catabolism of Glycine

Serine
● Following conversion to or from glycine, catalyzed by serine
hydroxymethyltransferase then dehydration/deamination to
pyruvate Figure 14. Catabolism of Cysteine
● Serine catabolism merges with glycine
Threonine
● Threonine aldolase cleaves threonine to acetaldehyde and
glycine
● Oxidation of acetaldehyde to acetate is followed by formation of
acetyl-CoA
● Threonine is dehydrated to -ketobutyrate which is converted
to propionyl CoA

Figure 15. Conversion of Threonine to Glycine

Figure 12. Catabolism of Serine

Alanine
● Transamination of alanine forms pyruvate
● Import ant in synthesis of non-essential AAs

Figure 13. Catabolism of Alanine Figure 16. Catabolism of Threonine

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D. Additional Amino Acids That Form Acetoacetyl-
CoA

Lysine
● This amino acid is exclusively ketogenic
● It is ultimately converted to aceto-acetyl CoA

Figure 18. Catabolism of Phenylalanine

E. Additional Amino Acids That Form Succinyl-CoA

Methionine
● Converted to SAM → major methyl group donor in one carbon
Figure 17. Catabolism of Lysine metabolism
● Source of Homocysteine
Tyrosine ● Clinical correlation:
● Following transamination of tyrosine to p- → Elevated homocysteine levels promotes oxidative damage,
hydroxyphenylpyruvate, successive reactions form inflammation and endothelial dysfunction; measure of
maleylacetoacetate, fumarylacetoacetate, fumarate, atherosclerosis
acetoacetate, and ultimately acetyl-CoA and acetate → Folate, Vit B12 and B6 → Decreases level of homocysteine
● Metabolic disorders → In pregnant woman → elevated homocysteine and
→ Type I Tyrosinemia (Tyrosinosis) - defect in decreased Vit. B increased incidence of neural tube defects
fumarylacetoacetate hydrolase
▪ Treatment: diet low in tyrosine and phenylalanine
▪ Untreated tyrosinosis may lead to death from liver failure
→ Type II Tyrosinemia (Richner-Hanhart syndrome) - defect
in tyrosine aminotransferase
→ Alkaptonuria - defect in homogentisate oxidase (catalyzes
conversion of homogentisate to maleylacetoacetate in
tyrosine catabolism)
▪ also called Black Urine Disease urine darkens on
exposure to air due to oxidation of excreted
homogentisate

Phenylalanine
● Phenylalanine is first converted to tyrosine via phenylalanine
hydroxylase
● Hyperphenylalaninemias
→ Type I (classic phenylketonuria, PKU) - arise from defects in
phenylalanine hydroxylase
→ Type II and III - defects in dihydrobiopterin reductase
→ Types IV and V - defects in dihydrobiopterin biosynthesis
● Treatment Figure 19. Methionine to Succinyl-CoA
→ Diet low in protein will prevent mental retardation of PKU
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Threonine
● This is dehydrates to alpha ketobutyrate which is converted to
propionyl coA

Figure 20. Threonine to Propionyl-CoA

Tryptophan
● Degraded to amphibolic intermediates via the kynurenine-
anthranilate pathway
● Tryptophan-2,3-dioxygenase (tryptophan pyrrolase) opens the
indole ring, incorporates molecular oxygen, and forms N-
formylkynurenine
● Hydrolytic removal of the formyl group of N-formylkynurenine,
Figure 22. Catabolism of Valine, Isoleucine, Leucine
catalyzed by kynurenine formylase, produces kynurenine
● Since kynureninase requires pyridoxal phosphate, excretion of
xanthurenate in response to a tryptophan load is diagnostic of Summary
vitamin B6 deficiency
● Hartnup disease reflects impaired intestinal and renal transport
of tryptophan
● The defect limits tryptophan availability for niacin biosynthesis
 pellagra like symptoms

Figure 21. Tryptophan Catabolism

F. Branched Chain Amino Acids

Isoleucine, Leucine, Valine

● These amino acids are known as branched-chain amino acids
● Very important amino acids because of the common illness
associated with it (which is the Maple Syrup Illness)
Figure 23. Summary of Amphibolic Intermediates that Result from the
● Branched chain α-keto acid dehydrogenase complex is a Catabolism of Protein Amino Acids
multimeric enzyme complex of a decarboxylase, a transacylase,
and a dihydrolipoyl dehydrogenase closely resembles pyruvate III. CONVERSION OF AMINO ACIDS TO SPECIAL
dehydrogenase
→ Its regulation parallels that of Pyruvate dehydrogenase, PRODUCTS
being inactivated by phosphorylation and activated by  Proteins play very important functional roles
dephosphorylation  Precursors to major biological materials
● The first 3 reactions of catabolism are analogous to reactions of  Heme
FA catabolism  Purine and Pyrimidine
→ 1-Branched chain amino acidaminotransferases  Hormones
→ 2-α-ketoacidDH/dehydrogenases  Neurotransmitters
→ 3-oxidase anddehydrogenase  Histamines
● Following transamination the carbon skeletons of the resulting  Amino Acids participate in more processes other than protein
keto acids undergo oxidative decarboxylation and conversion to synthesis
Coenzyme A thioesters
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Table 2. Example of different products from Amino Acids
Amino Acid Effector Molecule or Prosthetic Group
Immediate precursor of Urea
Arginine
Precursor of Nitric Oxide
Aspartate Excretory Neurotransmitter

Glycine Inhibitory neurotransmitter, precursor of heme

Histidine Precursor of Histamine

Precursor of serotonin and melatonin, smooth

Tryptophan
muscle contraction stimulator
Precursor of hormones and neurotransmitters,
Tyrosine cathecolomines, dopamine, epinephrine,
norepinephrine, and thyroxine

A. L- Amino Acids

 Alanine
 Serves as carrier of ammonia and of carbons of pyruvate
from skeletal muscle to liver via the Cahill cycle (glucose-
alanine cycle)
 Constitutes the free amino acid of plasma together with
glycine

Figure 25. Arginine Conversion to Special Products

 Cysteine
 Participate in the biosynthesis of CoA by reacting with
panthothenate to form 4-phosphopantothenoyl-cysteine
 3 enzyme catalyzed reactions convert cysteine to taurine
which can displace the CoA moiety of cholyl-CoA to form bile
acid taurocholic acid
 Conversion of cysteine to taurine is initiated by its
OXIDATION to cysteine sulfonate, catalyzed by the non-
heme Fe++ enzyme cysteine dioxygenase.
 DECARBOXYLATION of cysteine sulfinate will form
HYPOTAURINE
 Oxidation of Hypotaurine dehydrogenase will form
TAURINE
 Glutamylcysteine synthetase (with ATP) will form
glutathione

Figure 24. (a) Cahill Cycle (b) Cori and Cahill cycle

 Arginine
 Serves as carrier of nitrogen atoms in urea biosynthesis
 Guanidido group of arginine is incorporated to creatine
 After conversion to ornithine, its carbon skeleton becomes
that of putrescine, spermidine, and spermine
 Reaction catalyzed by Nitric oxide synthase forms NO
 A neurotransmitter, S.msc relaxant and vasodilator Figure 26. Cysteine Conversion 1/2

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 Serine
 Biosynthesis of sphingosine and purines and pyrimidines
 Provides carbon 2 and 8 of purine and the methyl group of
thymine
 Genetic defects in cystathionine Beta synthase, a heme
protein that catalyzes pyridoxi 5- phosphate dependent
condensation of serine and homocysteine homocystinuria

 Tryptophan
 Participates in the formation of serotonin which will also
leads in the formation of melatonin
 Serotonin has multiple physiologic roles: pain perception,
regulation of sleep, appetite temperature, blood pressure
and mood

Other Products
 Amino acid esters
Figure 27. Cysteine Conversion 2/2  PHOSPHOSERINE, PHOSPHOTHEREONINE AND
PHOSPOTYROSINE
 The phosphorylation and dephosphorylation of specific seryl,
 Glycine
threonyl and tyrosyl residues of protein regulate the activity
 Metabolites and pharmaceuticals excreted water soluble of enzymes of lipid and CHO met and of proteins that
glycine conjugates included glycocholic acid and hippuric participate in the signal transduction cascades
acid to form Benzoate  Sarcosine (N-methylglycine)
 Glycine can be incorporate into creatine  Its formation from dimethylglycine is catalyzed by
 The nitrogen and alpha-carbon of glycine is incorporated into flavoprotein dimethylglycine dehydrogenase which requires a
pyrrole rings and methylene bridges carbons of HEME pteroylpentaglutamate
 Entire glycine molecule becomes atom 4, 5, and 7 of purines  Can arise by methylation of glycine
 Catabolism of sarcosine to glycine catalyzed by
 Histidine flavoprotein sarcosine dehydrogenase
 Decarboxylation by pyridoxal 5 phosphate dependent
enzyme histidine decarboxylase yields HISTAMINE
 Biogenic amines that functions in allergic reaction and gastric
secretion, Concentration follows a circadian rhythm
 Other histidine in the body: ergothionine, carnosine and
dietary anserine
 Methionine
 Major non-protein fate is conversion to S-
adenosylmethionine principal source of methyl groups in
the body
 S-adenosylmethionine is synthesized from methionine and
ATP which is catalyzed by methionine adenosyltransferase
(MAT)
 3 MAT isozymes
 MAT1 and MAT3 of liver and MAT 2 is nonhepatic
 HYPERMETHIONINEMIA if decreased MAT 1 and 3
 Biosynthesis of spermine and spermidine
 These polyamines function in cell proliferation and growth
 Tyrosine
 Neural cells convert tyrosine to epinephrine and
norepinephrine (must know!!) Figure 29. Sarcosine synthesis
 Precursor of Triidothyronine and thyroxine  Creatine and Creatinine
 Formed from muscle creatine phosphate by irreversible,
nonezymatic dehydration and loss of phosphate
 24-hr urinary creatinine = proportionate to muscle mass
 Tells if collection is complete or not
 Glycine, arginine, and methionine all participate in creatine
biosynthesis

Figure 28. Tyrosine Conversion

Figure 30. Creatine-creatinine interplay

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 Synthesis is completed by methylation of guanidoacetate
 by S-adenosylmethionine
B. Non- Amino Acids
 Present in tissue in free form include
 β-alanine-Present in combined form in coenzyme A and in β-
alanyl dipeptides carnosine, anserine and homocarnosine
 β-amino isobutyrate
 ϒ-aminobutyrate (GABA)- Important neurotransmitter
 β-alanine
 formed during catabolism of pyrimidine URACIL
 Traces results from the hydrolysis of beta alanyl dipeptide by
enzyme Carnosine
 β-amino isobutyrate
 Also formed during the catabolism of pyrimidine THYMINE
 β-amino isobutyrate arise both from the a transamination of
methylmalonate semialdehyde and L-valine
 ϒ-aminobutyrate (GABA)
 GABA functions in brain tissues as an inhibitory
neurotransmitter by altering transmembrane potential
differences
 Decarboxylation of glutamate by L-glutamate decarboxylase
 Defect: 4 hydroxybutyric aciduria
 Parkinson’s disease
Figure 31. GABA synthesis from glutamate
IV. CASES
A.Phenylketonuria
Clinical Manifestations
● Phenylketonuria (PKU) is a genetic disorder that increases
phenylalanine in blood
● May be due to:
→ Defiecient activity of phenylalanine hydroxylase (PAH)
→ Deficiency of tetrahydrobiopterin as a co-factor
→ Enzyme defect in the recycling of tetrahydrobiopterin
● The action of PAH is to break down phenylalanine.
● Increased phenylalanine leads to brain damage
● Clinical manifestations include:
→ Intellectual disability
→ Epilepsy
→ Abnormalities in gait, sitting posture, and stance
→ Hyperactivity
→ Light pigmentation and eczematous rash
→ The body and urine may have a mousy odor due to
phenylacetic acid
→ However, onset of PKU is insidious and may not cause overt
symptoms until early infancy if undetected by neonatal
screening
BIOCHEMISTRY
Treatment/Management
● If detected, treatment should begin ASAP, before one week of
age
→ Treatment recommended if there is 7 to 10 mg/dL (420 to
600 mmol/L) of phenylalanine
→ Tetrahydrobiopterin (BH4) deficiency should be ruled out as
the cause of hyperphenylalaninemia
● Dietary restriction of phenylalanine
→ Involves the use of medical foods which are phenylalanine-
free protein substitutes
→ May also contain glycomacropeptides
→ Take note that optimal intake of protein free substitutes to
meat requirements for optimal growth and development is
still uncertain
→ These protein substitutes are not delicious and compliance to
diet is an issue
→ Lifelong dietary restriction results to good outcomes
● Tetrahydrobiopterin (BH4)/sapropterin
→ treatment for mild to moderate PKU
→ cofactor for PAH
→ used in conjunction with dietary restriction
→ aside from sapropterin, Pegylated phenylalanine ammonia
lyase (PEG-PAL), an enzyme that degrades phenylalanine,
is under investigation as possible treatment for PKU
B. Maple Syrup Urine Disease (MSUD)
Clinical Manifestations
● Enzyme defect: Branched chain ketoacid dehydrogenase
● The odor of urine in MSUD is like maple syrup or burnt sugar
● Biochemical defect is the involvement of alpha-keto acids
● Mutation is genes encoding E1 alpha, E1 beta, E2 and E3
● There are five distinct phenotypes of MSUD
→ Classic MSUD
▪ Present in newborns
▪ Most common disorder
▪ Mutation involves genes for E1-alpha, E1-beta, and E2
components of branched chain alpha ketoacid
dehydrogenase complex (BCKDC)
▪ Ketonuria, along with other symptoms such as poor
feeding, irritability, lethargy, and dystonia is observed
within 48 hours of birth
▪ By four days, more serious symptoms such as seizures
and cerebral edema are seen
▪ In some cases the initial symptoms do not appear until 7
days
▪ Breastfeeding delays onset of symptoms by 2 weeks
▪ In older infants or children under nutritional management,
metabolic intoxication can still occur in situations where
catabolism of endogenous protein is induced (stressful
situations (i.e., stressful situations)
▪ In the latter circumstances, symptoms such as epigastric
pain, vomiting, anorexia, muscle fatigue, pancreatitis,
hyperactivity, sleep disturbance, stupor decreased
cognitive function, dystonia, and ataxia.
▪ Furthermore, a clinical picture similar to Wernicke
encephalopathy is sometimes reported; death occurs by
edema and cerebral herniation
→ Intermediate MSUD
▪ Rare disorder associated in mutations with E1-alpha
component of BCKDC
▪ Present during infancy to childhood, especially during
episodes of stress
▪ Varying level of enzyme activity means that those with
greater enzyme activity presents symptoms at a later time
▪ Clinical signs are characterized by neurological
impairment and developmental delay
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→ Intermittent MSUD → Axillary and inguinal areas may have a brownish
▪ Second most common type of MSUD discoloration
▪ Present in infancy to childhood, especially during → Perspiration can stain clothing!
episodes of stress → Diagnosis is made if excreted urine appears normal but turns
▪ Patients have normal growth and development to black or brown if left standing or after alkalinization
▪ Symptoms manifest during periods of stress → Hence AKU is also called black urine disease
(ketoacidosis) → Diagnosis is confirmed by quantitative measurement of HGA
in urine, tyrosine levels are normal
▪ Aside from thiamine supplementation, dietary restriction of
branched-chain amino acids is needed to achieve Treatment/Management
metabolic control ● Dietary restriction of tyrosine and phenylalanine will reduce
→ Thiamine-responsive MSUD HGA excretion, but clinical effect is limited
▪ Very rare (one reported case of true thiamine-responsive → Arthropathy is slowed down, but previous damage is
MSUD) irreversible
▪ Involves E2 component of BCKDC ● Ascorbic acid inhibits the enzyme that catalyzes the oxidation of
▪ Present in infancy to childhood, especially during HGA to the polymer with affinity for collagen, but it’s not
episodes of stress demonstrated to be effective against ochronosis
▪ Clinical presentation similar to intermediate MSUD ● Nitisinone inhibits the second enzyme in tyrosine catabolic
→ E3-deficient MSUD pathway, decreasing HGA levels significantly.
▪ Presents rarely in adults, typically present in newborn → Still no clinical benefits
periods
▪ Mutations encoding E3 component of BCKDC Nice to Know!
▪ Lactic acidosis is sometimes a syndrome 5 Amino Acid Disorders Detected by New Born Screening in the
▪ Also have deficiencies in pyruvate and alpha-ketoglutarate Philippines
dehydrogenases - Arginosuccinuria
- Homocystenuria
Treatment/Management - MSUD
● Involves dietary therapy and prompt treatment of acute - PKU
metabolic decompensation - Tyrosenemia
● Dietary therapy; G6PD Deficiency – most common detected disease among
→ The goal is to achieve normal concentrations of branched Filipinos
chain amino acids, especially leucine, in plasma
→ Dietary restriction is maintained throughout life V. CONCLUSION
→ Thiamine supplementation is also done (TPP is a co-factor of
BCKDC)  Catabolism of AA begins with the removal of the alpha amino
group which is transferred to alpha-ketoglutarate and
C. Albinism oxaloacetate and excreted ultimately as UREA
Clinical manifestations  Resulting carbon skeletons: corresponds to various amino acid
can be derived from or fed into the glycolytic pathway, the TCA ,
● Albinism is homozygous defect in melanin production - either
fatty acid biosynthesis and gluconeogenesis therefore not an
due to lack of or defects in tyrosinase or accessory protein P
isolated pathway
● Clinical manifestations include:
→ Absence of color in the hair, skin, eye  Important and dynamic role not only as building blocks for the
→ Cross eye (strabismus), rapid eye movements (nystagmus), synthesis and turnover of proteins but in energy metabolism and
light sensitivity (photophobia, functional blindness as source for gluconeogenesis and reserve energy on
starvation
 AA provide precursors for the biosynthesis of a signaling
Treatment/Management molecules, hormones and neurotransmitters
● The goal of treatment is to relieve symptoms associated with
 Numerous inherited disorders are with AA metabolism
albinism.
● Interventions include
→ Protecting the skin and eyes from the sun (sunscreen, REVIEW QUESTIONS
covering up with clothing)
→ Glasses are prescribed to correct vision problems and eye from samplex
position 1. Amino acids that are strictly ketogenic
→ Sometimes surgery is done to correct nystagmus a. Lysine and leucine
→ Joining a support group b. Leucine and isoleucine
c. Valine and isoleucine
d. Tyrosine and tryptophan
D. Alkaptonuria (AKU) 2. Severe PKU and shortened lifespan is a result of
Clinical manifestations a. Excess dietary phenylalanine
● Autosomal recessive disorder resulting from deficient activity of b. Excess dietary tyrosine
homogentisic dioxygenase - the third enzyme in tyrosine c. Deficiency of dihydrobiopterin reductase
degradation d. Deficiency of tetrahydrofolate
● Clinical features include: 3. Alkaptonuria, an inborn error of tyrosine metabolism, is
→ Elevated levels of homogentisic acid (HGA) characterixed by darkening of the urine on exposure to air.
→ Ochronosis - pigmentation deposited in the connective tissue This is due to oxidation of excreted:
throughout the body a. Homogentisic acid
→ Asymptomatic in childhood and symptoms may show in the b. Hydroxyphenlypyruvate
third decade of life c. Maleylacetoacetate
→ IV discs are calcified, ochronotic arthritis and complete d. Fumarate
ankyloses
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4. Maple syrup urine disease is a metabolic disorder of REFERENCES
branched-chain amino acid metabolism. This is due to th
Harper’s Illustrated Biochemistry, 30 ed.
which of the following? Dr. Alba’s Lecture
a. Lack of leucine, isoleucine and valin aminotransferase 2020 Transcriptions
complex Leninger’s and Lippincott’s Biochemistry
b. Defective alpha-keto acid decarboxylase
c. Mutation of dihydrofolate reductase
d. Inability to attach the biotin coenzyme

5. Which of the following chemical reactions typically

initiates amino acid catabolism?
a. Glutamate dehydrogenation
b. Transamination
c. Transmethylation
d. Transulfuration

Answers: 1A, 2C, 3A, 4B, 5B

REFERENCES

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