Protein

metabolism
 Over view
• Proteins and amino acid
• Fate of amino acid
• In borne error of metabolism
• Gouts
Summary of protein digestion in the human body. Possible fates for
amino acid degradation products.
 Function of protein
1- Catalysts
Enzymes are protein molecules (generally designated by the
suffix -ase) that act as catalysts: they change the rate of reactions
occurring in the body.

2-Messengers
Some proteins are hormones. Hormones act as chemical
messengers. They are synthesized and secreted by endocrine
tissue (glands) and transported in the blood to target tissues or
organs, where they bind to protein receptors.
3- Structural elements
• contractile proteins ( actin and myosin)
• fibrous proteins ( collagen, keratin , bone, teeth, skin, tendons, nails, hair)
• globular proteins (myoglobin, calmodulin, and many enzymes.

• 4- IMMUNOPROTECTORS
• Immunoprotection is provided to the body in part by a
• group of proteins called immunoproteins, also called
• immunoglobulins (Ig) or antibodies (Ab). These immunoproteins,
• of which there are five major classes (IgG,
• IgA, IgM, IgE, and IgD),
5- TRANSPORTERS ( albumin, transferrin )
Transport proteins are a diverse group of proteins that
combine with other substances (especially vitamins and minerals,
but also other nutrients) to provide a means of carrying those
substances in the blood, or into cells, or out of cells, or within
cells.

6- BUFFERS
Proteins, because of their constituent amino acids, can serve as a
buffer in the body and thus help to regulate acidbase balance.
FLUID BALANCERS
In addition to acid-base balance, proteins (along with
other factors) influence fluid balance. The presence of protein in
the blood and in cells helps maintain fluid balance, or stated
differently, helps attract water and contribute to osmotic pressure.
 Amino acid calssification
• Structure

• Polarity

• Essentiality
 Structural classification
• all amino acids have a central carbon (C), at least one amino
group (—NH2), at least one carboxy (acid) group (—COOH),
and a side chain (R group) that makes each amino acid unique.
• The tendency of an amino acid to interact with water at
physiological pH—that is, its polarity—represents another
means of classifying amino acids.
• Polarity depends on the side chain or R group of the amino
acid.
 Essentiality of AA
• categorized the amino acids found in proteins as
nutritionally essential (indispensable) or nutritionally
nonessential (dispensable).

Previously only eight amino acids—leucine, isoleucine, valine,

lysine, tryptophan, threonine, methionine, and phenylalanine—
were considered essential for adult humans.
Histidine was later added as an essential amino acid.
Essentiality of AA
• Newer categories added to the essential/indispensable and
nonessential/ dispensable categories include
• conditionally or acquired indispensable amino acids.
• A dispensable amino acid may become indispensable if an
organ fails to function properly,
• (premature , disease-associated organ malfunction)
 Amino acid metabolism
• The liver is the primary site for the uptake of most
amino acids (about 50%–65%) following ingestion of
a meal.
• The liver is thought to monitor the absorbed amino
acids and to adjust the rate of their metabolism
(including catabolism, or breakdown of amino acids,
and anabolism, or use of amino acids for synthesis)
according to the needs of the body.
• Typically, of the amino acids entering the liver
after a meal, about 20% are used to synthesize proteins and
nitrogen-containing compounds;

• the rest is released into the plasma.

 Plasma protein
• Albumin, the most abundant of the plasma proteins,
is synthesized by the liver and released into the blood.

• A healthy person makes about 9 to 12 g albumin per day , half life 14-18
day

• Albumin in the plasma maintains oncotic pressure

and transports nutrients such as vitamin B6; minerals
including zinc, calcium, and small amounts of copper;
nutrients such as fatty acids; and the amino acid tryptophan.
Some drugs and hormones are also transported by albumin.
• Albumin is used with a few other proteins in the blood to assess an
individual’s protein status, specifically visceral (internal organ) protein
status.
• Two other proteins synthesized by the liver and released into
plasma are transthyretin (also called prealbumin) and retinol-
binding protein (which is complexed together and involved
with retinol, or vitamin A, and thyroid hormone transport).

• Transthyretin and retinol-binding protein, like

albumin, are used as biochemical indicators of visceral protein
status.

Half life 2 days- 2 and a half day

• Some of the other proteins made by the liver and
released into the blood are those needed for blood clotting, for
immunoprotection

α 1-globulins: glycoproteins, high-density lipoproteins

(for lipid transport)
α 2-globulins: glycoproteins, haptoglobin (for free hemoglobin
transport), ceruloplasmin (for copper transport and oxidase activity),
prothrombin (for blood coagulation), and very low density lipoproteins
(for lipid transport)
β-globulins: transferrin (for iron and other mineral transport)
and low-density lipoproteins (for lipid transport)
γ-globulins: immunoglobulins or antibodies (for immunoprotection)
• Other group o protein released during inflammation

• is called acute phase proteins or positive acute phase reactant

proteins. Some examples of these acute phase proteins are C-
reactive protein, fibronectin, orosomucoid (also called α 1 acid
glycoprotein), α 1 antitrypsin, haptoglobin, α 2 macroglobulin,
ceruloplasmin, metallothionein,
and serum amyloid A
• The body also generates another group of proteins,
called stress or (heat) shock proteins (abbreviated hsp).

• These proteins are synthesized in response to stress, including

heat stress and oxidative stress.
 Nitrogen-Containing Nonprotein
Compounds
• Nitrogen-containing nonprotein compounds or molecules, of
which several exist, are also synthesized in the liver (and often
in other sites) from amino acids and perform a number of
functions in the body.

• Glutathione Glutathione is a tripeptide synthesized from

three amino acids: glycine, cysteine, and glutamate.
• Glutathione is synthesized and found in the cytosol of most
cells of the body,
• It is a major antioxidant with the ability to scavenge free
radicals
• Creatine a key component of the energy compound creatine
phosphate, also called phosphocreatine, can be obtained from
foods (primarily meat and fish) or synthesized in the body.
Purine and Pyrimidine Bases
• Another group of compounds derived in part from amino acids
consists of purine and pyrimidine bases.
• Purine and pyrimidine bases are main constituents of two
nucleic acids—deoxyribonucleic acid (DNA) and ribonucleic
acid (RNA).

• The synthesis of the nitrogen-containing bases used to make

nucleic acids and nucleotides occurs for the most part de novo in
the liver.

• De novo synthesis refers to the synthesis of complex molecules

from simple molecules
PROTEIN SYNTHESIS
OVERVIEW
• Use of amino acids for anabolism occurs throughout the day,
but especially following meal ingestion (foods containing
carbohydrate, fat, and protein).

• Although protein synthesis typically predominates over

protein degradation after eating, the opposite becomes true
when food is not eaten. During prolonged periods in which
food is not eaten, such as during the overnight hours or a fast,
protein synthesis still occurs but at a much lower rate, and
protein degradation increases.

• Protien synthesis Affect and affected by many processes (page

207-210 FYI )
 Amino acids catabolism
• Liver cells have a high capacity for the uptake and catabolism
of amino acids. Catabolism of amino acids occurs to varying
degrees in different tissues both during fasting periods and
after eating.

• Different a.a. have different way and rate of catabolism

( BCAA catabolized much slower than other a.a
Steps of amino acid metabolism
1- Transamination and/or Deamination
of Amino Acids
the first step in the metabolism of amino acids not
used for the synthesis of proteins or nitrogen- containing
compounds is the removal of the amino group from the amino
acid.

• Deamination reactions involve only the removal of an amino

group, with no direct transfer to another compound.

• Transamination reactions involve the transfer of an amino

group from one amino acid to an amino acid carbon skeleton
2- Disposal of Ammonia—The Urea Cycle
• The urea cycle, functions in the liver and is important for the
removal of ammonia from the body.

• Too much ammonia in the body (as can occur with

liver failure) is toxic and can lead to brain malfunction and coma.

Ammonia in human body may come ( food, intestinal bac these

two sources enter the portal blood sources ( changed directly to
urea in the liver )
 Urea cycle
 Urea is the major end product in Nitrogen
metabolism in humans and mammals.
 NH3, the product of oxidative deamination
reaction, is toxic in even small amount and
must be removed from the body.
 Urea cycle is the conversion reactions of NH3 into
urea.
 Urea cycle
This reaction occur in liver (certain occur in
cytosol and mitochondria)
 The urea is transported to the kidney where it is
excreted.
 The overall urea formation reaction is :-
2 NH3 + CO2 + 3ATP ---> urea + H2O + 3 ADP
 Urea cycle
• Steps of urea cycle

1- Synthesis of carbamoyl phosphate ( need 2 ATP, enzymes,

irreversible)
• (condensation of NH4 + ions with CO2)
2- Formation of citrulline: intermediate in urea cycle
3- Synthesis of arginosuccinate ( need ATP)
4. Cleavage of arginosuccinate :
• cleaves to give arginine ( precursor of urea and fumarate.
5. Formation of urea
Fates of C skeletons of 20 amino acids.
• Carbon skeletons of amino acids can be further
metabolized with the potential for multiple uses in the cell.
An amino acid’s carbon skeleton, for example, can be used to
produce:
• Energy
• Glucose
• Ketone Bodies
• Cholesterol
• Fatty Acids
• all amino acids can be completely oxidized to
generate energy, not all amino acids can be used for synthesis of
glucose.

• Furthermore, the fate of the amino acid’s

carbon skeleton depends on the physiological nutritional state of
the body.
 Energy metabolism
Energy Generation The complete oxidation of amino acids
generates energy, CO2/HCO3 , and ammonia/ammonium.
Amino acids are used for energy in the body when diets are
inadequate in energy
 Glucose and Ketone
Body Production
• Gluconeogenesis occurs primarily in the liver but also in the
kidney.
• The carbon skeletons of several amino acids can be used to
synthesize glucose.
• the carbon skeleton of asparagine can be converted into
oxaloacetate
• the carbon skeletons of glycine, serine,
cysteine, tryptophan, and threonine can be converted into
pyruvate for glucose production in the liver.
• Some amino acids, such as phenylalanine and tyrosine, can be
degraded to form fumarate (an intermediate of the TCA cycle),
which can be used to form glucose, OR it can also converted
to acetoacetate, which can be used to synthesize ketone bodies.

• Thus, these two amino acids are both glucogenic

and ketogenic.

• AA considered a glucogenic amino acid, catabolism

of the amino acid must yield selected intermediates of
the TCA cycle.
 Regulations
• The conversion of amino acids to glucose
is accelerated by
1- High glucagon: insulin ratios
2- glucocorticoids such as cortisol ) hormones are
elevated when people are not receiving sufficient energy
or carbohydrate in the diet, in times of illness such as
occurs with infection or trauma,
3- In certain disease states such as untreated
diabetes mellitus and liver disease,
 Cholesterol Production
• Leucine is the only amino acid whose catabolism generates β-
hydroxy β- methylglutaryl (HMG) CoA, an intermediate in the
synthesis of cholesterol.

• Fatty Acid Production

In times of excess energy and protein intakes coupled with
adequate carbohydrate intake, the carbon skeleton of amino acids
may be used to synthesize fatty acids.
• The catabolism of aromatic, along with sulfur (S)-
containing, amino acids occurs primarily in the liver.

• In end-stage (or advanced) liver disease, the inability of the

liver to take up and catabolize these amino acids is evidenced
by the increased plasma concentrations of both the aromatic
amino acids—phenylalanine, tyrosine, and tryptophan—and
the S-containing amino acids methionine and cysteine.
 In borne error of protein
metabolism
• Nutrition therapy for amino acid disorders most commonly
consists of substrate restriction, which involves limiting one
or more essential amino acids to the minimum requirement
while providing adequate energy and nutrients to promote
typical growth and development
 In borne error of metabolism
• Hyperphenylalaninemai PKU
• Maple syrup urine MSUD
• Homocystinuria
 Phenylketonuria
• In this disorder phenylalanine (phe) is not metabolized to
tyrosine (Tyr) because of a deficiency or inactivity of
phenylalanine hydroxylase enzyme

• occur relatively frequent compared to other

• Has successful treatment

• PKU do not manifest any clinical signs of

abnormality in the immediate postnatal period,
• Diagnostic criteria for PKU include:

1- blood concentrations of Phenylalanine exceed

6 to 10 mgldl and Tyrocin concentrarions of less than 3 mg/dl.

• This abnormal levels affect the intellectual function

• blood Phe concentrations of greater than 20 mg/dl are the best

predictors of IQ loss.
 MNT
• Formula For PKU dietary therapy is planned around the use
of a formula/medical food with Phe removed from the protein.

• Most formulas/medical foods contain calcium. iron. and all

other necessary vitamins and minerals and are a reliable
source of these nutrients;

• The Phe-free formula and milk mixture should provide about

90% of the protein and 80% of the energy needed by infants
and toddlers.
 Formula
• Phenex1- , Phenex-2P, henex-2V anilla,
• Phenyl-Free2 , Periflex*

• Some formula called medical food (contain only protein free

of amino acid ( no fat, no CHO)
• To support metabolic control effectively,
formulas and medical foods must be consumed in
three or four nearly equal portions throughout the day.
 Diet recommendation
• Formula ( 80-90%)
• Foods of moderate- or low Phe content are used as a supplement to
the formula ( according to age)

• Low protein diet ( low protein pasta, bread)

• A phenylalanine intake of 60 mglkglday is chosen as a moderate

intake level.
• The prescription for phenylalanine must be adapted to individual
needs as judged by growth and blood levels.
• Children in 3 years Tolerance: 300- 400 mg of phenylalanine/day
( biochemical indicator)
PKU
MSUD
Elemental formula soy based milk
Low protein food
 Monitoring
Weekly or biweekly until 1 yr of age
Twice a month from 1 yr to 12 yrs
Monthly after 12 yrs of age
Weekly to biweekly during pregnancy
Diet records should be sent with every
spot – the type of food and amount are
listed as well as the phe/protein content
 0-6 months
0 to 4-6 months – formula combination of regular
infant formula/breast milk
4-6 months – start baby food and progress
normally, continue formula combo, start to
decrease infant formula/breast milk
6-12 month – continue to progress baby foods
(fruits, vegetables, cereal, puffs, depending on
infant start table foods), continue formula
 Food not allowed
MEAT – All kinds – meat, organ meat, processed meat

FISH – All kinds including shellfish, frozen or tinned.

EGGS – All kinds

CHEESE – All kinds including cheese spreads.

NUTS AND SEEDS

FLOUR-BASED FOODS e.g. bread, flour, cakes and biscuits
SOYA – Foods made from soya such as TVP (meat substitute)
ASPARTAME ( artificial sweetener ), E951
 Food allowed with caution
• Vegetables : potato, spinach, spring green peas, frozen starchy
vegetables (corn)
• Cereals
Rice krispies, oatmeal, rice.

Fruits : passion fruits

Dairy : Milk
Allowed in one serving /day
 Fruits and vegetables
apples
Apricots
figs (fresh,NOT dried)
Grapes
grapefruit
guava
kiwi fruit,
lemons, limes
mandarins
mango,
Melon
olives
oranges,
peaches,
pineapple,
pomegranate,
 Vegetables
• Artichoke
• Aubergine
• Cabbage
• Celeriac
• Coconut
• Garlic
• Cucumber
• Lady fingers
• Potato flour ( not potato)
• Tomato
 Cereals
• Cornflour
• Cassava flour
• Sago
• Tapioca
 Fat
• Fat without protein content
 Others
• Sugars
• Jam
• Honey

Food essences and colouring : vanilla, peppermint , almond,

Soy sauce : 2 tablespoons
Protein in infant formula
• Each scoop contain around 8.8 gm, 8.6gm, 8.5 gm
• Each small scoop contain: 4.3
• A pregnant woman with elevated blood Phe concentrations
endangers her fetus because of the amplified transport of
amino acids across the placenta.
• The fetus is exposed to about twice the Phe level contained in
normal maternal blood.

• Babies whose mothers have elevated blood Phe

concentrations have an increased occurrence of cardiac
defects, retarded growth, microcephaly, and mental
retardation,

• Strict control of maternal Phe levels before conception and

throughout pregnancy offers the best opportunity for normal
fetus growth
 MNT –PKU adult
• Many adults with PKU have had the benefits of early
diagnosis and treatment and are less likely to be affected by
neurologic damage. However, among those who have had
some degree of mental retardation, hyperactivity and selfabuse
are often major concerns.
 MSUD
• Maple syrup urine disease(MSUD) ,or branched-chaine keto
aciduria,
• results from a defect in enzymatic activity, specifically the
branched chain -ketoacid dehydrogenase complex.
• This decarboxylation defect prevents metabolism of
the branched-chain amino acids (BCAAs) leucine, isoleucine,
and valine

The severity of the disease depends on the severity of the enzyme

deficiency
• Maintenance of plasma leucine concentrations in
infants and preschool children should be as close to
physiologically normal as possible.

Concentrations above 10 mg/dl are often associated with a-

ketoacidemia and neurologic symptoms.
 Formula for MSUD
• Ketonex-I, Ketonex-2," BCAD l, BCAD
• 2,t MSUD Analog, Acerflexf
 MNT
• Several formulas specifically designed for the treatment of this
disorder they provide a reasonable amino acid and vitamin
mixture
• These are generally supplemented with a small quantity of
standard infant formula or cow's milk to provide the BCA A
needed to support growth
and development.
 Key Points
• Metabolic diseases, specifically PKU and MSUD, are serious
disorders that are life-threatening unless addressed promptly.
• Careful monitoring and adherence to dietary restrictions are
essential.
• Minor illnesses and infections must be taken seriously and
require special care.
• When a strict diet is initiated early and maintained well,
affected children can expect normal development and a normal
life span
 Homocystinuria
• Is a disorder of methionine metabolism, leading to an
abnormal accumulation of homocysteine and its metabolites
(homocystine, homocysteine-cysteine complex, and others) in
blood and urine

• Homocystinuria is an autosomal recessively inherited defect

• prevalence of 1 in 200,000 to 1 in 350,000 live births has been
estimated.
• The condition seems more common in New South Wales,
Australia (1 in 60,000 live births), and Ireland.
• Prenatal diagnosis is feasible by performing an enzyme assay
of cultured amniotic cells or chorionic villi or by DNA
analysis.
• Methionine is an essential, non-polar α-amino acid. Under
normal conditions methionine undergoes conversion to
homocysteine.
• This in turn undergoes trans- sulfuration to ultimately yield
cysteine.
• This step is catalyzed by the enzyme Cystathionine beta
synthase (CBS).
• People suffering from this disease are unable to synthesize
CBS, hence leading to an inability to metabolize methionine
• Due to the absence of CBS enzyme , homocysteine accumulates
in the blood serum leading to an increased excretion of
homocystine in the urine

• In normal people, Only approximately 20% of total

homocysteine (and its dimer homocystine) is in free form in the
plasma. The rest is bound to proteins as mixed disulfides.
•
• 3 major forms of homocystinemia an homocystinuria have
been identified
• Homocystinuria Caused by Cystathionine β-Synthase
Deficiency (Classic Homocystinuria)
• Homocystinuria Caused by Defects in Methylcobalamin
Formation
• Homocystinuria Caused by Deficiency of Methylene
tetrahydrofolate Reductase
• Homocystinuria Caused by Cystathionine β-Synthase
Deficiency ((ClassicHomocystinuria
• This is the most common inborn error of methionine
metabolism
• is an autosomal recessive inherited disorder
• Approximately 40% of affected patients respond to high doses
of vitamin B6 and usually have milder clinical manifestations
than those who are unresponsive to vitamin B6 therapy.
• These patients possess some residual enzyme activity
 Clinical manifistation
• Clinical manifestations during infancy are nonspecific and
may include: failure to thrive and developmental delay

• The diagnosis is usually made after 3 yr of age, when

subluxation of the ocular lens (ectopia lentis)occurs. retinal
detachment, and optic atrophy may develop later in life.

• Progressive intellectual disability is common

• Normal intelligence has been reported.  Higher IQ scores
are seen in vitamin B6 responsive patients

• Psychiatric and behavioral disorders ( 50% )

• Convulsions (20%)

• skeletal abnormalities resembling those of Marfan syndrome

they are usually tall and thin, with elongated limbs and
arachnodactyly
• Scoliosis, pectus excavatum or carinatum, genu valgum, pes
cavus, high-arched palate, and crowding of the teeth are
commonly seen

• These children usually have fair hair, blue eyes, and a peculiar
malar flush.
• Generalized osteoporosis, especially of the spine
Lenses dislocation
peculiar malar flush
Scoliosis: un even hips, un even
shoulders, curve in spine
pectus excavatum
genu valgum,
pes cavus
high-arched palate,
crowding of the teeth
 Complications
• Thromboembolic episodes  which is caused by changes in
the vascular walls and increased platelet adhesiveness
secondary to elevated homocystine levels

• Spontaneous pneumothorax and acute pancreatitis are rare

complications
 Diagnosis
• Elevations of both methionine and homocystine in body fluids
are the diagnostic laboratory findings.

• Freshly voided urine should be tested for homocystine because

this compound is unstable and may disappear as the urine is
stored.

• Cystine is low or absent in plasma

 Treatment
• high doses of vitamin B6 (200-1,000 mg/24 hr)  causes
dramatic improvement in most patients who are responsive
this therapy

• The degree of response to vitamin B6 treatment may be

different in different families
• Some patients may not respond because of folate depletion;
• a patient should not be considered unresponsive to vitamin B6
until folic acid (1-5 mg/24 hr) has been added to the treatment
regimen.
• Restriction of methionine intake in conjunction with cysteine
supplementation is recommended for patients who are
unresponsive to vitamin B6
• The treatment is different according to the type of the disease ,
the manifestation is different as well.

• But in general : high vitamin B6, folate, vitamin B 12, and

methionine supplementation
 Disorder of Urea cycle
metabolism
• All urea cycle defects result in an accumulation of ammonia in
the blood.
• The clinical signs of elevated ammonia are vomiting
and lethargy, which may progress to seizures, coma, and
ultimately death.

• In infants the adverse effects of elevated ammonia

levels are rapid and devastating.
In older children symptoms of elevated ammonia may be
preceded by hyperactivity and irritability.
• Neurologic damage may result from
frequent and severe episodes of hyperammonemia.

• The severity and variation of the clinical courses of some urea

cycle defects may be related to the degree of residual enzyme
activity
 0rnithine transcarbamylas (0TC)
deficiency
• X-linked recessive, blockagei n the conversion of ornithine
and carbamyl phosphate to citrulline.

• Severe OTC deficiency is usually lethal in males,

Where as heterozygous females with various degree of enzyme
activity may not demonstrates unless the symptoms induced by
stress ( infection, increase of protein intake)
 Other types
• Citrullinemia
• Argininosuccinaicc iduria( ASA)
• Carbamyl-phosphast syenthetase (C PS) deficiencies
 MNT
• Nutritional management of patients who have urea cycle
disorders is a challenging task

• The aim of therapy for the urea cycle disorders is to prevent

or decrease hyperammonemia and the detrimental neurologic
consequences associated with it
 Treatment
• Many
• Medication
• Hemodialysis
• Diet
 MNT
• Treatment is similar for all of the disorders.
• For mildly affected infants a standard infant formula can be
diluted to 1 to 1.5 g protein per kilogram of body weight per
day.
• The energy, vitamin, and mineral concentrations can be
brought up to recommended intake levels with the addition of
a protein-free formula.
• However, for most individuals, specialized
formulas are needed to adjust protein composition
in an effort to limit ammonia production.
 Protein Restricted Diets
• In general, low-protein or restricted-protein food patterns can
be formulated from readily available, lower protein infant,
toddler, and table foods.
Gout
• Gout is a common and complex form of arthritis that can
affect anyone. It's characterized by sudden, severe attacks of
pain, swelling, redness and tenderness in the joints, often the
joint at the base of the big toe

• Left untreated, gout can cause irreversible joint damage,

kidney problems, and tophi
 Gout
• The most common cause of inflammatory arthritis in adults
• Prevalence is greater in men t than women
• Prevalence has increased by 1.2% points over the past 2
decades
• Incidence of gout 2x greater among black men than white men
• Men with gout have been shown to have an increased risk of
all-cause mortality and cardiovascular disease mortality
• Caused by the deposition of monosodium urate crystals in
tissues
• Uric acid is a metabolic by-product of purine catabolism
• Purineshypoxanthinexanthineuric acid
• Reaction catalyzed by xanthine oxidase, found in the liver

• Purine precursors come from exogenous sources or

endogenous metabolism (synthesis and cell turnover
• When the balance of dietary intake, synthesis and rate of
excretion are disrupted, hyperuricemia results
o Overproduction (10%)
o Underexcretion (90%)
• Results in arthritis, soft tissue masses, nephrolithiasis
and urate nephropathy

• Nephrolithiasis (kidney stones) is a disease affecting

the urinary tract. Kidney stones are small deposits that
build up in the kidneys, made of calcium, phosphate and
other components of foods
• Acute uric acid nephropathy (AUAN, also acute urate
nephropathy) is a rapidly worsening (decreasing) kidney
function (renal insufficiency) that is caused by high levels
of uric acid in the urine (hyperuricosuria)
Pathophysiology
• Seafood high in purines: anchovies, herring, sardines, mussels,
scallops, trout, haddock, mackerel and tuna.
 Renal Complications
• Nephrolithiasis
o Risk factors: increase uric acid excretion, reduced urine volume, and low urine pH

• Chronic urate nephropathy

o Urate crystals can deposit in renal medullary interstitium producing inflammatory
changes and fibrosis
o Clinical features are non specific: renal function impairment, bland urinary sediment,
mild proteinuria and serum urate concentrations often higher than expected for the degree
of renal impairment.
o Biopsy confirms diagnosis