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MindMap Gallery Biochemistry and Molecular Biology - Biochemistry of the Liver
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Biochemistry and Molecular Biology - Biochemistry of the Liver
Biochemistry mind map of the liver in Chapter 19 of "Biochemistry and Molecular Biology" published by People's Medical Publishing House, including the structural characteristics of the liver, the role of the liver in material metabolism, the metabolism of bile pigments and jaundice, and the relationship between bile and bile acids. Metabolism etc.
Edited at 2023-11-03 15:26:50
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Biochemistry and Molecular Biology - Biochemistry of the Liver
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- Outline
Liver Biochemistry
Structural characteristics of the liver
Has dual blood supply from hepatic artery and portal vein
hepatic artery
Obtained from lungs and other tissues
oxygen
Metabolites
portal vein
obtained from the intestines
various nutrients
There are dual output channels of hepatic veins and biliary system
hepatic vein
connected to systemic circulation
Excrete metabolites or metabolic intermediates
biliary system
connected to the intestines
Excrete some metabolic waste
Excrete bile into the intestines
Rich liver sinusoids
Full material exchange between liver cells and blood
Liver cells are rich in organelles
Rich enzyme system
The role of liver in substance metabolism
Keep blood sugar levels relatively stable
Regulates glycogen synthesis and breakdown
synthesis
hexokinase
Phosphorylation of glucose to glucose-6-phosphate
Glucose-6-phosphate further synthesizes glycogen
break down
Glucose-6-phosphatase (muscle tissue🈚)
Convert glucose-6-phosphate directly to glucose
Glucose-6-phosphate comes from the breakdown of glycogen in the liver
gluconeogenesis pathway
The kidneys also perform gluconeogenesis
raw material
glycogenic amino acids
lactic acid
glycerin
Main path conditions
chronic starvation
Glycolysis pathway
aerobic oxidation of sugar
pentose phosphate pathway
Provides NADPH for liver biotransformation
Plays a central role in lipid metabolism
Oxidation of fatty acids
Synthesis and esterification of fatty acids
The production of ketone bodies
Intrahepatic Ketogenic External Hepatic Use
Cholesterol synthesis and transformation
The bile duct is almost the only way the body excretes cholesterol and its conversion products.
Hepatic synthesis of bile acids is the most important pathway for cholesterol degradation
Synthesis of lipoproteins and apolipoproteins
Heparin synthesis disorder
Affects the synthesis and secretion of VLDL
Impediment in intrahepatic fat transport and accumulation in the liver
One of the mechanisms of fatty liver disease
degradation of lipoproteins
The liver is the main organ that degrades LDL
Protein synthesis and metabolic breakdown are active
plasma protein metabolism
Synthesis and secretion of more than 90% of plasma proteins (except γ-globulin - from plasma cells)
Albumin
clotting factor
Severe liver cell damage may lead to prolonged coagulation time and bleeding tendency.
apolipoprotein
Clearance of plasma proteins (except albumin)
Amino acid metabolism
Breakdown and transformation of all amino acids except branched chain amino acids (leucine, isoleucine, valine)
Transamination
deamination
decarboxylation
Transmethylation
Detoxify ammonia
Ornithine cycle to synthesize urea
Severe liver disease, elevated blood ammonia, ammonia poisoning - leading to hepatic encephalopathy
Ammonia is converted to glutamine
Biotransformation of amines
Targeted
Aromatic amines such as phenethylamine and tyramine produced by decarboxylation of aromatic amino acids
mechanism
Oxidized and cleared by hepatic monoamine oxidase
In severe liver disease, aromatic amines enter the brain tissue through the blood-brain barrier and are hydroxylated to form phenylethanolamine and octamine (structures similar to catecholamines) - pseudoneurotransmitters - abnormal suppression of the brain - hepatic encephalopathy
Metabolism of multiple vitamins and coenzymes
Absorption of fat-soluble vitamins
Liver synthesis and secretion of bile acids
ADEK
vitamin storage
AEKB12
transport of vitamins
Retinol transport
Retinol is a type of vitamin A
维生素A1
视黄醇
维生素A2
3-脱氢视黄醇
Synthesis of retinol-binding protein
Vitamin D transport
Synthesis of Vitamin D Binding Protein
conversion of vitamins
carotene
Vitamin A
Vitamin PP
Coenzyme I (NAD) and coenzyme II (NADP)
Pantothenic Acid (Vitamin B5)
Coenzyme A (CoA)
Vitamin B1
Thiamine pyrophosphate (TPP)
Vitamin D3
25-hydroxyvitamin D3
Inactivation of multiple hormones
When liver cells are severely damaged, the hormone inactivation function is reduced, and the levels of estrogen, aldosterone, antidiuretic hormone, etc. in the body increase
疾病
男性乳房女性化
蜘蛛痣
肝掌（雌激素使局部小动脉扩张）
水钠潴留
water soluble hormone
Binds to specific receptors on the cell membrane and is internalized into liver cells for metabolic transformation.
fat soluble hormone
diffusion
Inactivated after combining with intrahepatic glucuronic acid or active sulfuric acid, etc.
Bile and bile acid metabolism
bile
Classification
liver bile
gallbladder bile
Liver bile is concentrated in the gallbladder
Main organic ingredients
Bile salts (highest content)
cholesterol
bile pigment
Various enzymes
bile acid
Classification
by structure
free bile acids
Cholic acid, chenodeoxycholic acid, deoxycholic acid, lithocholic acid
conjugated bile acids
Free amino acids glycine or taurine
Glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid
by source
primary bile acids
Bile acids directly synthesized in liver cells from cholesterol as raw materials, including cholic acid, chenodeoxycholic acid and their combination products with glycine or taurine
secondary bile acids
Under the action of intestinal bacteria, the bile acid generated by the deoxygenation of the alpha hydroxyl at position 7 of primary bile acid is called secondary bile acid, which mainly includes deoxycholic acid and lithocholic acid and their combination products with glycine or taurine respectively in the liver.
Main physiological functions
Promote the digestion and absorption of lipids (main function)
The three-dimensional configuration of bile acids - hydrophilic and hydrophobic sides, gives bile acids strong interfacial activity and becomes a strong emulsifier
Reduce the interfacial tension between oil and water phases
Maintain the dissolved state of cholesterol in bile to inhibit cholesterol precipitation (avoiding the formation of gallstones)
Whether cholesterol precipitates from bile depends primarily on the appropriate ratio of bile salts and lecithin to cholesterol in the bile
肝合成胆汁酸或卵磷脂的能力下降
消化道丢失胆汁酸过多
胆汁酸肠肝循环减少
排入胆汁中的胆固醇过多（高胆固醇血症）
Decreased ratio of bile acids and lecithin to cholesterol in bile (less than 10:1)
Cholesterol precipitation
gallstones
Bile acid metabolism and enterohepatic circulation of bile acids
Bile acid metabolism
Synthesis of primary bile acids
parts
In the cytosol and microsomes of liver cells
raw material
Cholesterol (main)
Glycine
Taurine
key enzyme
Cholesterol-7α-hydroxylase
Bile acid synthesis, a key enzyme for cholesterol breakdown
Synthesis
secondary bile acids
parts
Lower small intestine and large intestine
Synthesis
Enterohepatic circulation of bile acids
concept
After bile acids are discharged into the intestinal lumen with bile, about 95% can be reabsorbed into the liver through the portal vein, converted into conjugated bile acids in the liver, and then discharged into the intestinal lumen again through the biliary tract.
physiological significance
The limited bile acid pool (bile acid pool) (about 3 to 5 grams) is recycled to meet the body’s need for Physiological requirements for bile acids
Two modes of reabsorption of bile acids
What is not reabsorbed is derived into a variety of cholanic acids and is excreted in the feces.
conjugated bile acids
Actively reabsorbed in the ileum
free bile acids
Passively reabsorbed in various parts of the small intestine and large intestine
liver biotransformation
Overview of biotransformation
Biotransformation definition
The body metabolizes xenobiotics and some endogenous metabolites or biologically active substances to increase its water content. Soluble and polar, easily excreted from the body in the urine or bile
Biotransformation objects
Xenobiotic
Drugs, poisons, food additives, environmental pollutants, products of bacterial action in the intestine, etc.
endogenous substances
Hormones, neurotransmitters and other biologically active substances and their toxic metabolites
Main site of biotransformation
Liver - Mainly
Kidneys, lungs, gastrointestinal tract and skin
The meaning of biotransformation
Inactivate or detoxify (although poisoning is also possible)
Increase water solubility and polarity
Easily excreted from the body in urine or bile
Phase I biotransformation
reaction type
Oxidation
The monooxygenase system is the most important enzyme for oxidizing xenobiotics
Cytochrome P450 monooxygenase (CYP) system
又称羟化酶或混合功能氧化酶
目前已知底物最广泛的生物转化酶类
at least two components
Cytochrome P450 (heme protein)
NADPH-cytochrome P450 reductase
Flaviase with FAD as prosthetic group
position
Hepatocyte microsomes (smooth endoplasmic reticulum)
product
Hydroxide or epoxide
substrate
fat soluble substrate
Source of oxygen atoms
oxygen
Combined with clinical
Aflatoxin B1 is an important risk factor for primary liver cancer
Aflatoxin B1 generates aflatoxin 2, 3 epoxide through CYP action, which can be separated from DNA. guanine in the molecule binds, causing DNA mutations
Monoamine oxidase (MAO)
position
liver cell mitochondria
Catalytic reaction type
oxidative deamination
substrate
Aliphatic and aromatic amines
product
Aldehydes
Further oxidized to acid in the cytosol catalyzed by aldehyde dehydrogenase
Alcohol dehydrogenase and aldehyde dehydrogenase
Alcohol dehydrogenase (ADH)
position
hepatocyte cytoplasm
coenzyme
NAD
substrate
Alcohols
product
Aldehydes
Aldehyde dehydrogenase (ALDH)
position
mitochondria or cytoplasm
substrate
Aldehydes
product
Acids
reduction
enzyme
nitroreductase
azoreductase
product
Amines
substrate
Nitro compounds
Such as: nitrobenzene
Azo compounds
Such as: diazobenzene
hydrolysis
enzyme
Esterase
Hydrolysis of ester bonds
amidase
Hydrolysis of amide bonds
Glycosidase
Hydrolyze glycosidic bonds
Product features
Usually further transformation reactions are required before it can be excreted from the body.
substrate
ester
Amide
Glycoside
Phase II biotransformation
reaction type
binding reaction
Glucuronic acid conjugation (most important and common)
enzyme
UDP-glucuronosyltransferase (UGT)
position
liver microsomes
Direct donor of glucuronide group
Uridine diphosphate glucuronide (UDPGA)
source
substrate
Uridine diphosphate glucose (UDPG)
enzyme
UDPG dehydrogenase (NAD)
Combined with clinical
Glucuronolactone (Gantalox) treats liver disease
As a glucuronic acid preparation that increases hepatic biotransformation
Combine objects
Bilirubin, steroid hormones, morphine, and phenobarbiturates
sulfuric acid combination
enzyme
Sulfate transferase (SULT)
Cytoplasm
sulfate donor
3'-Phosphoadenosine-5'-phosphoryl sulfate (PAPS)
Example
Inactivation of estrone
Acetylation
Combine objects
Aromatic amines
enzyme
acetyltransferase
Cytoplasm
acetyl donor
Acetyl CoA
clinical
Isoniazid (anti-tuberculosis drug): cleared by acetylation inactivation catalyzed by intrahepatic acetyltransferase
glutathione binding
Combine objects
Halogenated, epoxide
enzyme
Glutathione S-transferase (GST)
Cytoplasm
significance
Important defense responses against electrophilic xenobiotics
GSH (Glutathione)
anti-oxidation
detoxification
Bind oxidative modification products to reduce their cytotoxicity
methylation reaction
Combine objects
Compounds containing nucleophilic groups such as oxygen, nitrogen, and sulfur
Enzymes (cases)
Catechol-O-methyltransferase (COMT)
Catalyzes the hydroxymethylation of catechols and catecholamines
active
Involved in the inactivation of dopamine
Methyl donor
S-adenosylmethionine (SAM)
Glycine
Combine objects
Carboxyl-containing compounds
Example
Hippuric acid production
Combine objects
Anything containing hydroxyl, carboxyl or amino groups
Characteristics of biotransformation reactions
Continuity of transformation reactions
Variety of reaction types
The duality of detoxification and detoxification
Factors affecting biotransformation
Age, gender, nutrition, disease and genetics have a significant impact on biological transformation
Human liver biotransformation enzymes have a developmental process
The biotransformation capacity of the liver in the elderly is still normal
Sex differences in certain biotransformation reactions
Nutritional status also affects biotransformation
Disease can affect liver biotransformation
Many xenobiotics induce biotransformation enzymes
Many xenobiotics can induce the synthesis of some biotransformation enzymes, while accelerating their own metabolic transformation. can also affect the biotransformation of other xenobiotics
Bile pigment metabolism and jaundice
Bile pigment metabolism
bile pigment
definition
Major catabolites of iron porphyrin compounds in the body
iron porphyrin compounds
hemoglobin
Myoglobin
Cytochrome
Catalase
peroxidase
type
biliverdin
Bilirubin
center of bile pigment metabolism
Main pigment in bile
orange yellow
lipophilic hydrophobic
ridge-like rigid folds
Powerful endogenous antioxidant, major component of antioxidant activity in serum
biliverdin reductase cycle
cholinogen
Bile hormone
Bilirubin metabolism
Bilirubin is mainly derived from the destruction of aging red blood cells
Degradation of hemoglobin
heme
Bilirubin is produced by degradation by cells of the mononuclear phagocytic system
globin
Decompose into amino acids for reuse
Production of bilirubin
enzyme
Heme oxygenase (HO)
position
Mononuclear phagocytic system cell microsomes
substrate
heme
product
biliverdin
3 isoenzymes
HO-1
The most inducible enzyme known to date
important cell protection mechanism
Diversity of inducing factors
HO-2
Induced only by glucocorticoids
HO-3
biliverdin reductase
position
Cytoplasm
hydrogen donor
NADPH
substrate
biliverdin
product
Bilirubin
Transport of bilirubin
Transportation form
Bilirubin-albumin complex
Competitive binding agents: sulfa drugs, salicylic acid, bile acids, etc.
Combine features
non-specific
non-covalent reversibility
significance
Increases the water solubility of bilirubin and improves plasma's transport capacity for bilirubin
temporary detoxification
Limits the free penetration of bilirubin through various cell membranes, avoiding its toxicity to tissue cells
Classification Bilirubin
conjugated bilirubin
unconjugated bilirubin
definition
Bilirubin is bound to albumin and transported in plasma without hepatic conjugation and conversion.
Features
There are intramolecular hydrogen bonds
Production and secretion of conjugated bilirubin
raw material
Bilirubin
generate
ingest
Bilirubin can freely and bidirectionally penetrate the surface of hepatic cell membranes in liver sinusoids and enter hepatocytes. The rate depends on the rate of albumin-bilirubin release and the ability of the liver cells to process bilirubin
transport
Binds to ligand protein (Y protein or Z protein, mainly Y protein) in the cytoplasm
Combined transformation
Production of bilirubin glucuronide
Each molecule of bilirubin contains 2 carboxyl groups and can be combined with up to 2 molecules of glucuronic acid.
excretion
Conjugated bilirubin is secreted from liver cells into bile canaliculi and then excreted into the intestine with bile.
transporter protein
multidrug resistance-like protein 2 (MRP2)
Features
Active transport process against concentration gradient
Hepatic secretion of bilirubin into bile canaliculi is the rate-limiting step in liver metabolism of bilirubin
Bilirubin is converted into cholinogen and cholin in the intestine
Bilibinogen is a product of conjugated bilirubin produced by enterobacteria
Remove glucuronic acid group and reduce
d-urobilinogen
Mesocholinogen
Further restoration
fecal bilinogen
The general name of the three substances is cholinogen
Oxidation of cholinogen to produce cholin
d-urobilin
i-urobilin
stercobilin
The three substances are collectively called bile
Bile hormone is yellowish brown and becomes the main color of feces
When the bile duct is completely obstructed, the feces will appear gray or white in color.
The intestinal bacteria of infants are sparse, and bilirubin that has not been acted upon by bacteria is excreted with the feces and appears orange.
Enterohepatic circulation of cholinogen
Minor part - urobilinogen
尿三胆
尿胆素原
尿胆素
尿胆红素
正常人尿中检测不到
There is a small amount of bilibinogen in the intestine that can be reabsorbed by intestinal mucosal cells and enter the liver through the portal vein. Most of the reabsorbed bilibinogen is then excreted into the intestine with bile.
Hyperbilirubinemia and jaundice
Normal human serum bilirubin content is very small
80% unconjugated bilirubin
20% conjugated bilirubin
Binds to albumin for temporary detoxification; binds to glucuronic acid for fundamental detoxification
Normal human liver has a strong ability to process bilirubin
jaundice
Hemolytic jaundice (prehepatic jaundice)
reason
Because red blood cells are destroyed too much in the monocyte-phagocytic system, more than liver cells The ability of uptake, conjugation, transformation and excretion results in excessive serum free bilirubin concentration.
Biochemical test characteristics
Increased plasma total bilirubin and unconjugated bilirubin levels
Urinary bilirubin negative
The levels of urobilinogen and urobilin increased, and the levels of urobilinogen and urobilin also increased.
hepatocellular jaundice
reason
Due to damage to liver cells, their ability to uptake, combine, transform and excrete bilirubin is reduced. Caused by low
Biochemical test characteristics
Serum unconjugated bilirubin and conjugated bilirubin were both elevated
Urinary bilirubin positive
Urobilinogen increases, but if the bile canaliculi are severely blocked, urobilinogen decreases instead
Fecal bilinogen levels are normal or reduced
obstructive jaundice
reason
Bile excretion channels are blocked due to various reasons, causing internal pressure in bile canaliculi and capillaries. Increased force ruptures, causing conjugated bilirubin to flow back into the bloodstream, causing an increase in serum bilirubin.
Biochemical test characteristics
Conjugated bilirubin was significantly elevated
Urinary bilirubin is positive, and the color of urine becomes darker, which may be the color of tea leaves.
Decreased fecal bilinogen and bile levels. Complete obstruction of the patient's stool turns gray or white clay color