Transcript Biochemistry of the liver - Univerzita Karlova v Praze

Biochemistry of the liver
Vladimíra Kvasnicová
The figure was adopted from http://faculty.washington.edu/kepeter/119/images/liver_lobule_figure.jpg (April 2007)
The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_003.jpg (April 2007)
The figure is from: Color Atlas of Biochemistry / J. Koolman, K.H.Röhm. Thieme 1996. ISBN 0-86577-584-2
Central position in energy and
intermediary metabolism
• regulation of blood concentration of many
metabolites
• regulation of storage and production of energy
• synthesis of molecules for other tissues
• interconversion of nutrients
• storage of some substances
• formation and secretion of bile
Glucose in the liver can be
a) transformed to fatty acids
b) stored in glycogen molecules
c) oxidized to acetyl-CoA
d) used for production of NADPH
Metabolism of saccharides
• glucostatic function of the liver
• glycogen synthesis, glycolysis
• glycogen degradation, gluconeogenesis
• glucokinase, glc-6-phosphatase
• pentose cycle
• Cori cycle and glucose-alanine cycle
Metabolism of saccharides (II)
• excess of glucose  FFA  TAG
• transformation of saccharides to glucose
• metabolism of fructose (fructokinase)
• synthesis of amino saccharides
• synthesis of uronic acids
• degradation of insulin and glucagon
The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_004.jpg (April 2007)
Fatty acids entering the liver can be
a) used for synthesis of TAG
b) transformed to glucose
c) transformed to ketone bodies
d) oxidized to CO2 and H2O
Metabolism of lipids
• liver controls blood FFA concentration
• energy is produced mainly by -oxidation
• synthesis of ketone bodies
• synthesis of TAG (from FFA, glc, AA)
• synthesis of cholesterol
• synthesis of bile acids
• synthesis of phospholipids
• synthesis of VLDL and HDL
• degradation of plasma lipoproteins
The figure is from: Color Atlas of Biochemistry / J. Koolman, K.H.Röhm. Thieme 1996. ISBN 0-86577-584-2
The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_006.jpg (April 2007)
Choose the correct statement(s) about
the metabolism of lipoproteins in the
liver:
a) the hepatocyte synthesizes
chylomicron particles
b) triacylglycerols leave the liver
incomporated in VLDL
c) apoproteins are synthesized in the
liver
d) LDL transports cholesterol from
peripheral tissues to the liver
Amino acids in the liver can be
a) used for synthesis of clotting factors
b) used for synthesis of immunoglobulins
c) transformed to glucose (only glucogenic
amino acids)
d) decomposed, urea is one of the main
products
Metabolism of N-containing compounds
• synthesis of plasma proteins (except Ig)
• synthesis of coagulation factors
• synthesis of acute phase reactants
• degradation of amino „N“ (urea, Gln)
• synthesis of nonessential amino acids
• metabolism of aromatic AAs
• degradation of purines to uric acid
• synthesis of creatine
• conjugation and excretion of bilirubin
The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_005.jpg (April 2007)
HOOC
COOH
N
H
N
H
Bilirubin
O
N
H
N
H
O
a) belongs among linear tetrapyrrols
b) is excreted mainly with bile
c) is soluble in water after its
conjugation, e.g. with glucuronic acid
d) is called „direct bilirubin“ if it is
bound to albumin
The figure is from: Color Atlas of Biochemistry / J. Koolman, K.H.Röhm. Thieme 1996. ISBN 0-86577-584-2
excretion
The figure was adopted from http://connection.lww.com/Products/porth7e/documents/Ch40/jpg/40_007.jpg (April 2007)
Causes of
hyperbilirubinemia
1) increased bilirubin
formation
2) decreased bilirubin
uptake by hepatocyte
3) deficit in conjugation
4) defect of active
transport to bile
5) biliary obstruction
The figure was adopted from the book: Klinická biochemie - požadování a hodnocení BCH vyšetření /
J. Masopust (Karolinum 1998)
cause
jaundice
BILI in
serum
prehepatic
hemolytic
 indirect
no


liver
 both:
indirect
and direct
yes


 direct
yes
no
no
hepatic
posthepatic obstructive
BILI in
urine
UBG in
urine
UBG in
feaces
indirect = unconjugated = insoluble in water (= fat soluble) = bound to albumin
direct = conjugated = soluble in water
Metabolism of vitamins
• provitamins vitamins, storage of vitamins
• carotenes  vitamin A
• 25-hydroxylation of provitamin D (→ calcidiol)
• cleavage of side chain of vitamin K
• storage of vitamin B12
• synthesis of nicotinic acid from Trp
• formation of coenzymes from B vitamins
Metabolism of minerals
• storage of iron (ferritin)
• storage and metabolism of other trace elements
(Cu, Mn, Co, Mo, Zn,..)
• synthesis of transport proteins
(transferrin, ceruloplasmin)
• deiodation of thyroidal hormones → I- (iodide)
Metabolism of hormones
• degradation and excretion
(see 3rd semester)
Metabolism of xenobiotics
• see next seminar
Metabolic
pathways in
different zones
of the liver
lobule
The figure was adopted from
http://www.tharu.com/academic/html/newcastle/liver.htm
(April 2007)
a) periportal hepatocytes - higher pO2:
• more mitochondria, less ER
• blood contains a lot of O2 and nutriens
• more of oxidative reactions
• antioxidative defense (glutathion)
• CC, RCH, oxidative phosphoryl., -oxidation
• urea synthesis
• glukoneogenesis
• cholesterol synthesis
• proteosynthesis
b) perivenous hepatocytes - lower pO2:
• blood contains few O2 and nutriens
• more of reductive reactions
• synthesis of lipids
• glycogen synthesis
• ketogenesis
• biotransformation of xenobiotics (sm. ER)
• detoxification of NH3: synthesis of Gln
Glutamine
cycle
in the liver
The figure was adopted from: Devlin, T. M. (editor): Textbook of Biochemistry with Clinical Correlations, 4th ed. Wiley-Liss, Inc.,
New York, 1997. ISBN 0-471-15451-2
Choose the mtb pathway(s) proceeding
only in the liver:
a) gluconeogenesis
b) ketogenesis
c) synthesis of urea
d) synthesis of bile acids
Choose correct statement(s) about
enzymes of hepatocytes
a) ALT participates in a metabolism
of amino acids
b) ALP belongs among esterases
c) LD needs NADH as a coenzyme
d) AST catalyzes one of reactions
of a pentose cycle
Liver tests
•
total bilirubin (‹ 22 M)
•
ALT (‹ 0,75 kat/L)
•
AST (‹ 0,75 kat/L)
•
ALP (‹ 2,29 kat/L)
•
GMT (men: 0,25-1,77, women: 0,17-1,10 kat/L)
the values are used in FNKV