BIOCHEMISTRY

METABOLISM IN THE URINARY SYSTEM

Dr. Dra. TRINI SURYOWATI, MS

 Objectives :

• Metabolic function of the kidney

-- Renal gluconeogenesis
-- Role of the kidneys in amino acid metabolism

• Indocrinal function of the kidney

-- Calcitriol hormone synthesis
-- Eritropoetin hormone synthesis
-- Renin hormone synthesis
Amino acid
FUNCTION
An Introduction to the Urinary System
UREA DALAM URIN
Function of the Urinary System
• Excretion & Elimination:
removal of organic wastes products from body
fluids (urea, creatinine, uric acid)
• Homeostatic regulation:
• Water -Salt Balance
• Acid - base Balance
• Endocrine function:
• Hormones
KREATININ DALAM URIN
The main roles of the kidney

• Participation in amino acid / nitrogen metabolism

• Excretion of water, salts, and waste products (urea,
uric acid…)
• Regulation of electrolyte and acid-base balance
(homeostasis)
• Participation in biosyntheses (creatine, carnitine,
glucose, AA)
• Participation in hormonal regulation
FUNGSI GINJAL
• Ekskresi dan homeostatis berada di bawah kontrol
hormon
• Ginjal berperan pada pembentukan beberapa
hormon.
• Ginjal juga mengambil alih fungsi metabolisme
intermedier, terutama pada pemecahan asam
amino dan pada glukoneogenesis.
METABOLIK GINJAL
AA/nitrogen metabolism during fasting

• During fasting, AA are released from skeletal muscle: Ala,

Gln
• Sk. muscle oxidizes Val, Ile, Leu to produce energy and
Gln
• The amino groups of Val, Ile, Leu, Asp, and Glu are
transferred out of skeletal muscle in Ala and Gln

• Ala supplies gluconeogenesis in the liver

• Gln is taken up by the kidney and gut
METABOLISM
 The composition in
ultrafiltration, secretion and resorption
AA/nitrogen metabolism during fasting

Ala supplies gluconeogenesis in the liver, Gln

is taken up by the kidney and gut
Branched-chain AA
Branched-chain AA
BCAA are the major AA that can
be oxidized in tissues other than
liver

α- keto acids of the BCAA are

either released into the blood
and taken up by liver, or
oxidized to CO 2, or converted
to Gln
 Gln and Ala as nitrogen carriers
• Gln is generated mainly in the skeletal muscle from Leu, Ile, Val, and
also by the lungs and brain from the removal of NH 4 + :
Glu + ATP + NH 4 + -> Gln + H 2 O + ADP + P

• The kidney, the gut, and cells with rapid turnover rate (e.g. cells of the
immune system) are the major sites of Gln uptake

• Gln serves as a fuel and a nitrogen donor for syntheses;

• In the kidney, the glutaminase reaction is particularly important

• Much of the unused nitrogen from Gln is built into Ala which carries the
nitrogen to the liver where it is converted to urea
Ammonia release in the kidney
• 1) By glutaminase

• 2) By glutamate dehydrogenase α -ketoglutarate is used as a fuel by

the kidney:
oxidized to CO 2 or converted to glucose
Glutamine as a fuel for the
kidney
• The carbon skeleton of Gln
forms α- ketoglutarate, which
is oxidized to CO 2, converted
to Glc, or released as S or A
• Glucose is used principally by
the cells of the renal medulla
• Lactate is oxidized in renal
cortical cells which have a
higher mitochondrial capacity
and a greater blood supply
Ammonium is excreted into the urine
Creatinin excretion

Creatine phosphate can readily

Creatine phosphate is unstable and
regenerate ATP
spontaneously cyclizes, forming
creatinine, which is excreted in the
urine
FUNGSI HORMONAL GINJAL
FUNGSI HORMONAL GINJAL
ERITROPOIETIN
SISTEM RENIN
RENIN ANGIOTENSIN SYSTEM
RENIN ANGIOTENSIN SYSTEM
AKTIVITAS VITAMIN D (KALSIFEROL)
NORMAL VITAMIN D METABOLISM
VITAMIN D DEFICIENCY
METABOLISME INTERMEDIER
• Urin yang mengalami pemekatan/ terkonsentrasi
dan transportasi menembus membran adalah proses yang
memerlukan banyak energi, karena itu banyak memerlukan ATP

Pada tubuli proksimal diperlukan ATP yang berasal dari proses oksidatif
asam lemak, benda keton dan beberapa jenis asam amino. -
METABOLISME INTERMEDIER
• Perlu laktat, gliserol dan asam lemak, dalam jumlah lebih sedikit.
• Pada tubuli distalis dan ansa Henle, glukosa merupakan sumber
utama energi untuk keperluan metabolisme.
• Sel indotel dari tubuli proksimal mempunyai kemampuan untuk
berlangsungnya jalur glukoneogenesis, untuk ini diperlukan substrat
dari karboksilat dari asam amino
METABOLISME INTERMEDIER
• Gugus amino diperlukan dalam bentuk ammonia untuk proses buffer
pada urin
• Enzim untuk degradasi peptida dan katabolisme asam amino
mempunyai aktivitas yang tinggi pada ginjal
• (mis : amino acid oksidase, amin oksidase dan glutaminase
GLUCONEOGENESIS
 GLUCONEOGENESIS
• Medula ginjal mempunyai banyak mitokondria sehingga glikolisis
banyak berlangsung
• Ginjal mempunyai cukup enzim gliserolkinase, fosfoenolpiruvat
karboksilase maka glikoneogenesis merupakan proses utama yang
mempergunakan laktat dan gliserol.

• Disamping hati, ginjal adalah satu satunya organ yang mempunyai

enzim glukosa 6-fosfatase yang menghirolisa glukosa 6 fosfat dan
melepaskan glukosa ke darah (meninggikan glukosa darah) untuk
sampai kejaringan lain.
 DIET FOR DELAY DIALISIS
• Bakteri usus dapat memecah urea menjadi ammonia, yang dengan
asam keto (intermediate TCA) , hati mensintesanya menjadi asam
amino non esensial.

• Diet karbohidrat dalam jumlah yang secukupnya dan asam amino

dibatasi sedapat mungkin hanya asam amino esensial dapat
menurunkan sintesa aa non esensial (cara ini merupakan dasar untuk
memperlambat dialisis).
NUTRITION ON KIDNEY DISEASE
NUTRITION ON KIDNEY DISEASE
METABOLISM
SYMPTOMS OF HIGH CREATININ
Feeling Dehydrated
Fatigue
Nausea
Swelling
Breathlessness
Muscle Cramps
Loss Of Libido
Visual Disturbances

Foods to avoid.
FOODS TO ENJOY...AND REDUCE
CREATININ
GOUT DIETARY and LIFESTYLE
GUIDELINES

Advice for people with gout generally consist of the following, but
consult your doctor for individual guidance
LIFESTYLE GUIDELINES
CONTROL URIC ACID
LIFESTYLE GUIDELINES
CONCLUSION
• Renal endocrinal function :
-- The kidneys synthesize Calcitriol, a hormone crucial for
calcium homeostasis
-- The kidnyes synthesize EPO, a hormone crucial for
Erytropoesis
-- The kidnyes synthesize Renin, a hormone crucial for
maintaining blood pressure through the renin angiotensin
system
CONCLUSION
• Renal metabolic function :

-- The kidneys are involved in gluconeogenesis

-- The kidneys are involved in amino acid metabolism

REFERENCES
• 1. Thomas M Devlin, Text book of Biochemistry With Clinical
Correlation Sixth Edition, Wiley Liss 2006
• 2. J.Koolman, Colour Atlas of Biochemistry, Large 2006 3.Stefan
Silbernagel. Colour Atlas of Pathophisiology, New York. Thieme 2000
REFERENCES
Good luck