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Page 1: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Biochemistry ofhuman organs and tissues

Page 2: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Organs and tissues

- digestive tract- blood and immune system- liver- adipose- kidney- muscles- connective tissues- brain, senses

Page 3: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

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)

CO2CO

2

HCO3- + H+

HCO3-

Cl–

Cl–

APT→ADP+Pi K+

H+K+

Cl–

CA

K+

Page 4: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Digestive tract

Pancreatic juice- neutralization of gastric acid (HCO

3

–)

- digestive function (trypsin, chymosin, elastase,carboxypeptidase, α-amylase, lipase, colipase, phospholipase, nucleases, ...)

lipasecolipase

triacylglycerol

di/monoacylglycerol

bile acid

Page 5: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Digestive tract

Bile - emulgation (bile acids)- neutralization of gastric acid (HCO

3

–)

Intestinal juice- digestive function (peptidases, glycosidases, lipases,

phospholipases, nucleases etc.)

fructoseglucose

glucosegalactose

Na+

APT→ADP+Pi

K+

Na+K+

Na+

fructoseglucose

Na+

Glut-5

SGLT Glut-2K+ K+

Page 6: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Lipid resorption, resynthesis, lipoproteins

Fatty acids

monoacyl-glycerol

glycerol

Fatty acids

monoacyl-glycerol

glycerol

acyl-CoA

ligase

triacylglycerols

chylomicron

chylomicron

Page 7: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Lipid resorption, resynthesis, lipoproteins

Composition: triacylglycerols, cholesterol, phospholipids,proteins (1-50 %, apoproteins)

chylomicron

intestine

chylomicronremnant

Fatty acids formuscles andadipose tissue

Liver

VLDL

IDL

HDL

Activated by HDL

Activated by HDL

Fatty acids formuscles andadipose tissue

CETP

LDL

cholesterol

Page 8: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Lipid resorption, resynthesis, lipoproteins

HDL: transports cholesterol to liver for degradation“good cholesterol”

LDL: transports cholesterol to cells“bad cholesterol”

CETP – cholesterol ester transfer proteinTorcetrapib:November 30, 2010 – "This will be one of the most important compounds

of our generation” Jeff Kindler, Pfizer’s chief executiveDecember 2, 2010 – Pfizer announces halt of phase III clinical

trials of Torcetrapib

HDL

LDL

Page 9: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Blood

Roles: - transport of oxygen, carbon dioxide, other nutrients- water distribution- acidobasic homeostasis- thermoregulation- immunity- self-protection (blood coagulation)

Composition: ~45% of cellular elements

Hematopoiesis: bone marrow, fetal spleen and liver

centrifugationcoagulation

centrifugation

blood plasma serum

Page 10: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Blood

Composition of serum:- salts (mostly Na+, Cl-, 0.15M NaCl, 0.9% NaCl)- glucose, lactate, urea, amino acids,

triacylglycerols, cholesterol- proteins 6-8%

albumin – colloidal, transport and osmotic function

+–

α1α

2β γ

albumin

sample

Page 11: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Blood

Oxygen transporthemoglobin – allosteric effect

Oxygen pressure

saturation

Page 12: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Blood

Erythrocyte metabolism

glucose

glucose

lactate

lactate

NADPH

Reduced glutathion

Reductionof ROS

NADHReducedcyt-b5

HemoglobinFe2+

2,3-bisP-glycerateweakerO

2 binding

Page 13: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Blood

Blood groups AB0

H A B

GalNAc

Gal

GlcNAc

Fru

acceptor A (anti-B) B (anti-A) AB ( - ) 0 (anti-A, anti-B) donor

A - A - AB A - - AAB A A - A0 - - - -

Page 14: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Immunity

Innate immunity vs. adaptive immunity

cellular immunity vs. humoral immunity

Innate immunity:macrophages

granulocytes

NK-cells

perforin

Fc-receptor

Page 15: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

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

Page 16: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Immunity

adaptive immunity

T-cell

antigen-presentingcell

MHC

T-cellreceptor

Page 17: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Immunity

adaptive immunity

antigen-presenting cell macrophage almost all cellsB-lymphocytes

MHC MHC class II. MHC class I.

T-lymphocyte helper cytotoxic

role activation of attacking of viral-antigen-presenting infected or cancerB-cells, production cell by perforinof soluble and granzyme,antibodies start of apoptosis

Page 18: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Liver

Function: - input of nutrients from small intestine- metabolism of saccharides, lipids, amino acids etc.- storage (glycogen, B12, iron)- detoxification- bile excretion- hormone transformation

glucose

glucose

glycogen

lipids

lipids

lipids

glucose

lactate

ketone bodiescholesterol

bile

aminoacids

urea

Page 19: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Liver

lipids

glucose

AcCoA AcAcCoA HMGCoA

AcAcOH

acetone

3-hydroxybutyrate

cholesterolfatty acids

cholesterolester

triacylglycerole

lipoproteins

+ H+

Page 20: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Liver

Cytochrom P450

R-H + O2 + NADPH + H+ → R-O-H + H

2O + NADP+

hydroxylation, epoxidation, dealkylation, oxidation of N, S, P etc.~60 isoformsCYP 3A4, 2C19, 1A2, 2A6, 2B6 are major drug metabolizessterole metabolism

NADPH

FAD

FMN

heme

NADPH

FAD

FMN

heme

FeS

Endoplasmatic reticulum mitochondria

Page 21: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Liver

ethanol metabolism

high energy inputhigh NADH/NAD+ ratiosuppression of citric acid cycle, lactate synthesis, acidosislactate in blood reduces clearance of uric acidhigh production of keton bodieshigh lipid productiondegradation of ethanol by microsomal alcohol oxidase

(one of CYP isoenzyme)

ethanol acetaldehyde acetate AcCoANADH NADH –ATP

Page 22: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Muscles

Skeletal muscles

ATP

ADPADP

ADP

acetylcholinemuscarinic receptor

import of Na+

release of Ca2+ fromsarcoplasmatic reticulum

Page 23: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Muscles

creatine

Page 24: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

glucose

glucose

NADPH AcCoAglycerol

acyl-CoA

fatty acid

albumin

lipoproteins

triacylglycerol

lipoprotein lipaseAdipose

Page 25: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

glucose

glucose

NADPH AcCoAglycerol

acyl-CoA

fatty acid

albumin

lipoproteins

triacylglycerol

lipoprotein lipase

+

+

+

–+

insulincatecholamines

Adipose

Page 26: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Adipose

Enough or too much fat Lack of fat

Productionof leptin

hypothalamus

Neuropeptide Yfeeling of hunger

Productionof leptin

hypothalamus

Neuropeptide Yfeeling of hunger

Page 27: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Adipose

Insulin resistance:obesity, high concentration of free fatty acids in blood

switch from glucose metabolism to fatty acid metabolismin many tissues

lack of absorption of glucose

high glucose concentration in blood, type II diabetes

Page 28: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Kidney

hypothalamus

vasopresin

GPCR aquaporin

water resorption

Page 29: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Kidney

renin

prorenin

cleavage

angiotensinogen angiotensin I (10 AA)

angiotensin II (8 AA)cleavage

in bloodcleavagein blood

Angiotensin-converting enzyme (ACE)

Retention of water and Na+

Vasocontriction,high blood pressure

productionof hormones

cleavagein blood

low blood pressurelow Na+ concentration

Page 30: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Nervous system

neurotransmitter

ion channel GPCRDegrading enzyme

resorption

degradation

Page 31: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Nervous system

Neurotransmitters

acetylcholine +/– M,I CNS and PNS AChEsterase

glutamate + I CNS resorptionglycine – I CNS resorptionGABA – I CNS resorption, metab.dopamine +/– M CNS and PNS resorption, metab.noradrenalin +/– M CNS and PNS resorption, metab.adrenalin +/– M CNS and PNS resorption, metab.serotonin +/– M,I CNS resorption, metab.histamine +/– M CNS resorption, metab.

endorphins, enkephalinsdynorphins – M CNS cleavage

adenosine, ATP helper M CNS resorption

+ activatin– inhibitonI ionotropic (Na+, K+, Cl–)M metabolotropic (cAMP, Ca2+)

Page 32: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Nervous system

Neurotransmitters

acetylcholine +/– M,I CNS and PNS AChEsterase

glutamate + I CNS resorptionglycine – I CNS resorptionGABA – I CNS resorption, metab.dopamine +/– M CNS and PNS resorption, metab.noradrenalin +/– M CNS and PNS resorption, metab.adrenalin +/– M CNS and PNS resorption, metab.serotonin +/– M,I CNS resorption, metab.histamine +/– M CNS resorption, metab.

endorphins, enkephalinsdynorphins – M CNS cleavage

adenosine, ATP helper M CNS resorption

+ activatin– inhibitonI ionotropic (Na+, K+, Cl–)M metabolotropic (cAMP, Ca2+)

Paralytic gassesantialzheimer

drugs

Amphetamins,antidepressants

AmphetaminsAmphetamins,kokain

antidepressants

opiates

coffein

Page 33: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Nervous system

Neurotransmitter degradersAcetylcholine esterase

acetylcholine + H2O → acetate + choline

monoamine oxidase, COMT

Page 34: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Hormones

Chemistry:- peptides, steroids, amino acid derivatives

Role:- metabolism, growth, differentiation, homoeostasis, digestion etc.

Distance of action:- endocrine, paracrine, autocrine

Page 35: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Hormones

Steroid hormones:hormone

nucleus

mRNA,protein

Page 36: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

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

Page 37: Biochemistry of human organs and tissuesold-biomikro.vscht.cz/vyuka/abio/06_tissues.pdf · 2012. 12. 18. · human organs and tissues. Organs and tissues - digestive tract - blood

Hormones

Peptide hormones:Insulin – 30+21 amino acids – glycogen metabolismGlucagon – 29 amino acids – glycogen metabolismAngiotensin II – 8 amino acids – blood pressureVasopressin – 9 amino acids – blood pressure, water resorptionOxytocin – 9 amino acids – uterine contraction, milk ejectionGrowth hormone, ACTH, Ghrelin, Neuropeptide Y, ...

Other hormones:Thyroxine – thermogenesis, basal metabolism, embryonic development