Download Biochemistry of human organs and tissues

Biochemistry of
human organs and tissues
Organs and tissues
- digestive tract
- blood and immune system
- liver
- adipose
- kidney
- muscles
- connective tissues
- brain, senses
Digestive tract
Saliva - digestive function (α-amylase)
- protective function (antibodies, lysozyme)
- other functions (mucin – rheological properties)
Gastric acid - digestive function (HCl, pepsin, chymosin, lipase)
- absorption of nutrients (haptocorrin, intrinsic factor)
- other functions (mucin)
CO2
CO2
CA
Cl–
HCO3-
Cl–
HCO3- + H+
K+
APT→ADP+Pi
K+
H+
K+
Cl–
Digestive tract
Pancreatic juice
- neutralization of gastric acid (HCO3–)
- digestive function (trypsin, chymosin, elastase,
carboxypeptidase, α-amylase, lipase, colipase,
phospholipase, nucleases, ...)
colipase
lipase
bile acid
di/monoacylglycerol
triacylglycerol
Digestive tract
Bile
- emulgation (bile acids)
- neutralization of gastric acid (HCO3–)
Intestinal juice
- digestive function (peptidases, glycosidases, lipases,
phospholipases, nucleases etc.)
fructose
glucose
glucose
galactose
Na+
Glut-5
SGLT
fructose
glucose
Na+
APT→ADP+Pi
K+
Na+
Na+
K+
K+
K+
Glut-2
Lipid resorption, resynthesis, lipoproteins
Fatty acids
Fatty acids
acyl-CoA
monoacylglycerol
glycerol
ligase
chylomicron
monoacylglycerol
chylomicron
glycerol
triacylglycerols
Lipid resorption, resynthesis, lipoproteins
Composition: triacylglycerols, cholesterol, phospholipids,
proteins (1-50 %, apoproteins)
intestine
LDL
chylomicron
Activated by HDL
cholesterol
Liver
IDL
chylomicron
remnant
Fatty acids for
muscles and
adipose tissue
VLDL
CETP
Activated by HDL
Fatty acids for
muscles and
adipose tissue
HDL
Lipid resorption, resynthesis, lipoproteins
HDL: transports cholesterol to liver for degradation
HDL
“good cholesterol”
LDL: transports cholesterol to cells
“bad cholesterol”
CETP – cholesterol ester transfer protein
Torcetrapib:
LDL
November 30, 2010 – "This will be one of the most important compounds
of our generation” Jeff Kindler, Pfizer’s chief executive
December 2, 2010 – Pfizer announces halt of phase III clinical
trials of Torcetrapib
Blood
Roles: - transport of oxygen, carbon dioxide, other nutrients
- water distribution
- acidobasic homeostasis
- thermoregulation
- immunity
- self-protection (blood coagulation)
Composition: ~45% of cellular elements
blood
centrifugation
plasma
coagulation
centrifugation
Hematopoiesis: bone marrow, fetal spleen and liver
serum
Blood
Composition of serum:
- salts (mostly Na+, Cl-, 0.15M NaCl, 0.9% NaCl)
- glucose, lactate, urea, amino acids,
triacylglycerols, cholesterol
- proteins 6-8%
sample
β γ
α
α
albumin 1 2
–
albumin – colloidal, transport and osmotic function
+
Blood
Oxygen transport
hemoglobin – allosteric effect
saturation
Oxygen pressure
Blood
Erythrocyte metabolism
glucose
Reduced glutathion
glucose
Reduction
of ROS
NADPH
2,3-bisP-glycerate
lactate
NADH
lactate
Reduced
cyt-b5
weaker
O2 binding
Hemoglobin
Fe2+
GalNAc
Blood
Gal
Blood groups AB0
GlcNAc
Fru
H
acceptor
donor
A
B
AB
0
A
B
A (anti-B)
B (anti-A)
AB ( - )
0 (anti-A, anti-B)
A
A
-
A
A
-
-
A
A
A
-
Immunity
Innate immunity vs. adaptive immunity
cellular immunity vs. humoral immunity
Innate immunity:
macrophages
granulocytes
Fc-receptor
NK-cells
perforin
Blood
Immune system
Antibodies
IgA – mostly in intestinal fluid and other secrets
IgD – B-lymphocyte receptor
IgE – allergy-related
IgG – ~75 % of all Igs in blood
IgM
T-cell
Immunity
adaptive immunity
MHC
T-cell
receptor
antigenpresenting
cell
Immunity
adaptive immunity
antigen-presenting cell
macrophage
B-lymphocytes
almost all cells
MHC
MHC class II.
MHC class I.
T-lymphocyte
helper
cytotoxic
role
activation of
antigen-presenting
B-cells, production
of soluble
antibodies
attacking of viralinfected or cancer
cell by perforin
and granzyme,
start of apoptosis
Liver
Function: - input of nutrients from small intestine
- metabolism of saccharides, lipids, amino acids etc.
- storage (glycogen, B12, iron)
- detoxification
- bile excretion
glucose
- hormone transformation
lipids
urea
glycogen
glucose
lipids
amino
acids
lactate
glucose
lipids
bile
ketone
bodies
cholesterol
Liver
glucose
AcCoA
AcAcCoA
HMGCoA
+ H+
lipids
AcAcOH
fatty acids
cholesterol
acetone
cholesterol
ester
triacylglycerole
3-hydroxybutyrate
lipoproteins
Liver
Cytochrom P450
R-H + O2 + NADPH + H+ → R-O-H + H2O + NADP+
NADPH
NADPH
FAD
FAD
FMN
FMN
FeS
heme
Endoplasmatic reticulum
heme
mitochondria
hydroxylation, epoxidation, dealkylation, oxidation of N, S, P etc.
~60 isoforms
CYP 3A4, 2C19, 1A2, 2A6, 2B6 are major drug metabolizes
sterole metabolism
Liver
ethanol metabolism
ethanol
NADH
acetaldehyde
NADH
acetate
–ATP
AcCoA
high energy input
high NADH/NAD+ ratio
suppression of citric acid cycle, lactate synthesis, acidosis
lactate in blood reduces clearance of uric acid
high production of keton bodies
high lipid production
degradation of ethanol by microsomal alcohol oxidase
(one of CYP isoenzyme)
Muscles
acetylcholine
muscarinic receptor
Skeletal muscles
import of Na+
release of Ca2+ from
sarcoplasmatic reticulum
ATP
ADP
ADP
ADP
Muscles
creatine
Adipose
lipoprotein lipase
albumin
glucose
lipoproteins
triacylglycerol
fatty acid
NADPH
acyl-CoA
glucose
glycerol
AcCoA
Adipose
lipoprotein lipase
albumin
insulin
catecholamines
glucose
lipoproteins
+
triacylglycerol
+
+
–
fatty acid
glucose
+
NADPH
acyl-CoA
glycerol
AcCoA
Adipose
Enough or too much fat
Production
of leptin
Lack of fat
Production
of leptin
hypothalamus
hypothalamus
Neuropeptide Y
feeling of hunger
Neuropeptide Y
feeling of hunger
Adipose
Insulin resistance:
obesity, high concentration of free fatty acids in blood
switch from glucose metabolism to fatty acid metabolism
in many tissues
lack of absorption of glucose
high glucose concentration in blood, type II diabetes
Kidney
hypothalamus
vasopresin
GPCR
aquaporin
water resorption
low blood pressure
low Na+ concentration
Kidney
prorenin
cleavage
Angiotensin-converting
enzyme (ACE)
renin
angiotensinogen
cleavage
in blood
Retention of water
and Na+
angiotensin I
(10 AA)
production
of hormones
cleavage
in blood
cleavage
in blood
angiotensin II
(8 AA)
Vasocontriction,
high blood pressure
Nervous system
degradation
neurotransmitter
resorption
ion channel
GPCR
Degrading enzyme
Nervous system
Neurotransmitters
acetylcholine
+/–
M,I
CNS and PNS
AChEsterase
glutamate
glycine
GABA
dopamine
noradrenalin
adrenalin
serotonin
histamine
+
–
–
+/–
+/–
+/–
+/–
+/–
I
I
I
M
M
M
M,I
M
CNS
CNS
CNS
CNS and PNS
CNS and PNS
CNS and PNS
CNS
CNS
resorption
resorption
resorption, metab.
resorption, metab.
resorption, metab.
resorption, metab.
resorption, metab.
resorption, metab.
M
CNS
cleavage
helper M
CNS
resorption
endorphins, enkephalins
dynorphins
–
adenosine, ATP
+ activatin
– inhibiton
I ionotropic (Na+, K+, Cl–)
M metabolotropic (cAMP, Ca2+)
Nervous system
Neurotransmitters
Paralytic gasses
antialzheimer
AChEsterase
drugs
acetylcholine
+/–
M,I
CNS and PNS
glutamate
glycine
GABA
dopamine
Amphetamins,
noradrenalin
antidepressants
adrenalin
serotonin
histamine
+
–
–
+/–
+/–
+/–
+/–
+/–
I
I
I
M
M
M
M,I
M
CNS
resorption
CNS
resorption
CNS
resorption, metab.
CNS and PNS
resorption, metab.
Amphetamins
CNS and PNSAmphetamins,
resorption, metab.
CNS and PNS kokain
resorption, metab.
CNS
resorption, metab.
antidepressants
CNS
resorption, metab.
M
CNS
cleavage
helper M
CNS
resorption
endorphins, enkephalins
opiates
dynorphins
–
coffeinATP
adenosine,
+ activatin
– inhibiton
I ionotropic (Na+, K+, Cl–)
M metabolotropic (cAMP, Ca2+)
Nervous system
Neurotransmitter degraders
Acetylcholine esterase
acetylcholine + H2O → acetate + choline
monoamine oxidase, COMT
Hormones
Chemistry:
- peptides, steroids, amino acid derivatives
Role:
- metabolism, growth, differentiation, homoeostasis, digestion etc.
Distance of action:
- endocrine, paracrine, autocrine
Hormones
hormone
Steroid hormones:
nucleus
mRNA,
protein
Hormones
Steroid hormones:
Corticosteroids – produced by adrenal cortex
- cortisol – lipolysis, proteolysis, gluconeogenesis,
immunosuppressive
- aldosterone – function of kidney, reabsorption of Na+
Sexual steroids:
♂ Androgens – testosterone
♀ Estrogens – estradiol
♀ Gestagens – progesterone
Hormones
Peptide hormones:
Insulin – 30+21 amino acids – glycogen metabolism
Glucagon – 29 amino acids – glycogen metabolism
Angiotensin II – 8 amino acids – blood pressure
Vasopressin – 9 amino acids – blood pressure, water resorption
Oxytocin – 9 amino acids – uterine contraction, milk ejection
Growth hormone, ACTH, Ghrelin, Neuropeptide Y, ...
Other hormones:
Thyroxine – thermogenesis, basal metabolism, embryonic
development