Chapter 1 Structure and function of proteins
Peptide unit (plane) 肽单元（平面）
An amide plane consists of six atoms ,Cα1, C, O, N, H, Cα2 on the same plane.
The partial double-bond character of the peptide bond makes Cα1, C, O, N, H, Cα2 six atoms coplanar, Cα1 and Cα2 are trans to each other, this semi-rigid plane composed of those six atoms is termed as peptide unit.
Primary structure 一级结构
From N to C terminus, The linear sequence (orarrangement ) of amino acidsthat are covalently linked bypeptide bonds.It also includes the locationsof -S-S- bonds
The AA sequence from N end to C end in the polypeptide chain(s) of a protein
Numbering AA sequence from N to C end
Forces that stabilize the primary structures are covalent bonds— peptide bonds and disulfide bonds (if present).
The AA sequence of a protein is determined by its gene
Secondary structure 二级结构
the localized folding segments of the polypeptide backbone
Common secondary structures:
α-helix (α螺旋)
β- pleated sheet (β折叠)
random coil (无规卷曲)
β –turn(bend)(β转角)
Forces: hydrogen bonds
Tertiary structure 三级结构
the spatial, three-dimensional arrangement of all atoms in a polypeptide chain, resulting from the interactions between the R groups of protein chains. A functional structure of protein that consists of one peptide chain.
Quaternary structure 四级结构
(1) Proteins contain two or more separate polypeptide chains. Each folded to a complete tertiary structure is called subunit.
(2) Association of two or more subunits to form a functional protein
(3) Subunits may be identical or not
Motif (模体)
Motifs are the assembling of more than 2 secondary structural elements that fold to near each other in space and have special functions.
Domain 结构域
The tertiary structure of some proteins can be divided into 2 or more relatively independent compact regions that may be joined by a flexible segment of the chain, and have special functions. These compact units called domains
Isoelectric point(pI)---等电点
pI is the pH at which protein molecular becomes electrically neutral, has no net electric charge
Denaturation of protein 蛋白质变性
Protein spatial structure is sensitive to denaturing agents, these agents result in unfolding and disorganization of protein spatial structure without change in primary structure, and associate with loss of biological activity.
Denatured proteins:
no peptide bond broken
biological activity is partially or completely lost, sensitive to protease effect
physical and chemical properties changed
usually the solubility is reduced
Chapter 2 Enzymes
Enzyme (酶)
Enzymes are highly efficient biocatalysts which are involved in almost all biological reaction.
Enzymes are proteins in chemical nature. They have special conformation and can be denatured.
Some RNA/DNA has enzyme activity, which are called Ribosome
Active center of enzyme (酶的活性中心)
Active site is a three-dimensional, local region of the enzyme, the region is composed of several essential groups of AAs, that has special spatial structure which specifically binds substrate and catalyzes it to become product. Coenzymes or prosthetic groups can be involved in active site.
Allosteric regulation of enzyme (酶的变构调节)
Binding of allosteric effector to allosteric site can change the E conformation and activity (activation or inhibition), and allosteric regulation is a fast effect. An allosteric activator increases the enzyme activity, while an allosteric inhibitor decreases the activity of an enzyme.
Covalent modification of enzyme (酶的共价修饰)
The structure and activity of many enzymes can be altered reversibly through covalent modification by another enzyme.
the most common modification: phosphorylation / dephosphorylation--- addition and removal of a phosphate group.
Fast control of enzyme activity.
Zymogen and activation of zymogen (酶原及酶原激活)
Some enzymes are synthesized and secreted as large inactive precursors called zymogens or proenzymes.
Zymogens are activated by the irreversible hydrolysis one or more peptide bonds and forming or exposing the active site in the E molecule
Isozymes (同工酶)
One group of enzymes catalyze the same reaction.
Have different protein structure, physicochemical and immunological properties
Present in the same species, the same individual body or same cell, encoded by the same gene or different genes.
Competitive inhibition 竞争性抑制作用
the inhibitor(I) structure is similar to S
The I reversibly competitively binds to the active site of E
I only binds to free E and competes with S
Vmax: unchanged
apparent Km (Kmapp,表观Km): increased affinity of E for S is decreased
Inhibition is reversible as high[S] competes for I
Noncompetitive inhibition 非竞争性抑制作用
the I binds reversibly at a site other than the active site, the binding of I by E has no effect on the binding of S by E.
The I binds at a different site to the S
Vmax: decreased
apparent Km (Kmapp,表观Km): unchanged
affinity of E for S is unchanged
Inhibition cannot overcome by increasing [S]
Chapter 3 Metabolism of carbohydrates
Glycolysis (糖酵解) : An anaerobic oxidation from G to Pyruvate and then to lactate.
Glycolytic pathway (糖酵解途径)：oxidation from G to Pyruvate is same in both aerobic oxidation (有氧氧化)and anaerobic oxidation (无氧分解).
Tricarboxylic acid cycle,TCA (Citric acid cycle / Krebs cycle)
include 8 reactions Oxaloacetate + acetyl-CoA and then
4 dehydrogen reactions 2 decaboxylation reactions 1 substrate-level phosphorylation
And at last Oxaloacetate is reformed.
Gluconeogenesis(糖异生)
The glucose or glycogen molecules can be produced in liver from non-carbohydrate such as lactate, pyruvte, amino acid and glycerol largely through reverse pathway of glycolysis .
blood glucose（血糖）
Blood sugar is referred to the concentration of glucose in the blood. Normal value of blood glucose is 3.89-6.11 mmol/L
Substrate-level phosphorylation (底物水平磷酸化)
The transfer of the high-energy phosphoryl group of high- energy substrate (eg. glycerate-1,3-bisphosphate) to ADP, then ATP is formed.
Lactate cycle (Cori cycle ) (乳酸循环)
Cori cycle is a mechanism for meeting the glucose needs at exercise. Muscles at work produce lactate from glycolysis when oxygen becomes limiting. Lactate is transported from the muscles to the liver via the bloodstream. In the liver, lactate is converted (gluconeogenesis) back to glucose, where it is dumped back into the bloodstream for transport to muscle.
Chapter4 Metabolism of Lipids
Essential Fatty Acids（必需脂肪酸）
Essential means that animals cannot synthesize it in a sufficient level to meet their requirement
Must be supplied in the diet
Be necessary for normal functions of the body:
As component of the phospholipids in cell membranes, Precursor for prostaglandins and other important metabolic regulator
e.g. linoleic acid, linolenic, arachidonic acid
Mobilization of triacylglycerol（脂肪动员）
Triacylglycerols stored in adipose tissue are hydrolyzed, the products glycerol and fatty acid are transported to the tissues, in which fatty acids can be oxidized for energy production. The principal enzyme in mobilizing stored fat is triglyceride lipase, which is hormone-sensitive TG lipase(HSL).
b-Oxidation of fatty acids（脂肪酸的b氧化）
In the matrix of mitochondrion, fatty acyl-CoAs are oxidized in a series of cycles that each cycle release two carbons from the carboxyl in the form of acetyl-CoA. Each cycle involves four reactions-dehydrogenation, hydration, dehydrogenation, and thiolytic cleavage.
Ketone body（酮体）
Ketone bodies include acetoacetate, acetone, and β-hydroxybutyrate. They are intermediates of FA oxidation, formed in mitochondria of liver and exported to extrahepatic tissues to be oxidized and utilized.Overproduction results in ketoacidosis.
Citrate pyruvate cycle（柠檬酸- 丙酮酸循环）:
to transport acetyl-CoA from mitochondrial matrix to cytosol.
Reverse cholesterol transport, RCT(胆固醇的逆向转运)
HDL transports cholesterol from tissues & other lipoproteins to the liver, which can excrete excess cholesterol as bile acids.
The cholesterol is scavenged from cell surfaces & from other lipoproteins with the help of ABCA1 (ATP-binding cassette transporter A1) .
Formation of CE in HDL by LCAT and transfer of CE from HDL to other lipoproteins by CETP.
Cholesterol-rich lipoprotein can be taken up by liver & degraded.
Chapter 5 Biological Oxidation
Biological oxidation(生物氧化)
The oxidation take place in organism is termed biological oxidation. It mainly refers to the enzymatic steps in the oxidative degradation of carbohydrates, fats, and amino acids to CO2 , H2O and energy. Some of the energy is used for the generation of ATP from ADP and Pi, and the other is released as heat energy.
Respiratory chain ( electron transport chain)（呼吸链）
The mitochondrial respiratory chain consists of a series of enzymes with prosthetic groups capable of accepting and donating either one or two electrons, most of which are membrane-bonded proteins. Each component of the chain can accept electrons from the preceding carrier and transfer them to the following one, in a specific sequence.
Oxidative phosphorylation （氧化磷酸化）
The process of the enzymatic phosphorylation of ADP to ATP coupled to electron transfer from a substrate to molecular oxygen is termed Oxidative phosporylation.
P/O ratio（磷/氧比值）
When isolated mitochondria are suspended in a buffer containing ADP, Pi, and an oxidizable substrate, oxygen and Pi are consumed at the same time.
In Oxidative phosphorylation, when consume one mole O, the mole consuming Pi is the P/O ratio. That is the number of ATP from consuming one O.
Chapter 6 Metabolism of amino acids
One carbon unit （一碳单位）
Some of reaction in amino acids catabolism can produce one-carbon group, that include:
methyl (-CH3) group
methylene (-CH2-) group
methenyl (-CH=) group
formyl ( -CHO) group
formimino (-CH=NH) group
they can not exist freely, and must be carried by tetrahydrofolate (THF, or FH4).
One-carbon units are used as the precursors for purine and pyrimidine synthesis.
Putrefaction of protein（蛋白质的腐败作用）
The proteins of undegestion and the products residue are acted by intestinal bacterial in the large intestine. most of putrefaction products are toxic. Most of them are excreted in feces , less get into liver through portal vein.
Alanine-glucose cycle （丙氨酸-葡萄糖循环）
To transport NH3 in the nontoxic forms of alanine from muscles to liver.
Essential amino acids（必需氨基酸）
Some of amino acids that can not be synthesized by human , must be obtained in the diet to meet body’s metabolic. (8 kinds )
Val Leu Ile Thr Lys Ser Phe Met
Chapter 7 Metabolic interrelationships and regulation
The allosteric regulation of key enzymes(变构调节)
small allosteric effectors, which generally have little or no structural similarity to the substrate, binding to allosteric site of the enzyme by non-covalent bonds triggers changes in enzyme conformation that alter the catalytic capacity of the enzyme. An allosteric activator increases the enzyme activity, while an allosteric inhibitor decreases the activity of an enzyme.
The regulation of chemical modification of enzymes（化学修饰）
Some groups on apoenzyme can be catalyzed by other enzymes, occuring reversible covalent modification then change the enzyme activity.
phosphorylation and dephosphorylation
Methylation and demethylation
Acetylation or deacetylation
Adenylation or deadenylation
SH or -S-S
Allosteric enzymes（变构酶）
It is a kind of enzymes with allosteric regulation, and most of allosteric E have several subunits （multiple subunits）.The regulatory (allosteric) site and the catalytic site are on separate or same subunits
limiting velocity enzymes(限速酶)
In a group of reactions, the lowest step is the limiting velocity step, the key step. Its regulation can affect the whole reactions, and this enzyme is limiting velocity enzyme.
Chapter 8 Hemal biochemistry
Porphyria (卟啉症)
Disorders that arise from defects in the enzymes of heme biosynthesis.
The intermediates content in heme synthesis elevate in the serum and urine.
The porphyria are both inherited and acquired disorders(lead or drugs toxicosis).
Chapter 9 liver biochemistry
Biotransformation(生物转化)
The nonnutritional substances are converted to more polar metabolites by various chemical reaction ,and promoted their excretion from body.
exogenous compounds: drugs,food additives, toxicity,and environmental pollutants etc.
endogenous compounds: hormone, neurotransmitter, amines,ammonia，putrefactional
products etc.
Phase II reaction: conjugation reaction（第二相反应）
In phase 2, the hydroxylated or other compounds produced in phase 1 are convened by specific enzymes to various polar metabolites by conjugation.
Most of these enzymes are in the cytosol.
Generally occur at a higher rate than phage I reaction.
conjugation reaction (-OH,COOH,NH3)with Glucuronic acid,sulfate, acylation, Glutathione (GSH) , Methylation
bile acid(胆汁酸)
accoding to the Source: Primary bile acid - synthesis in liver
Secondary bile acid - synthesis in intestine
accoding to the Structure: Cholic acid GlycoCholic acid
TauroCholic acid
Chenodeoxycholic acid Taurochenodeoxycholic acid
Glycochenodeoxycholic acid
Enterohepatic circulation of bile acid（胆汁酸的肠肝循环）
Bile acids is secreted from the liver through bile ducts into the intestine, where they aid the emulsification of dietary lipids. then bile acids are reabsorbed (passive and active) in the lower small intestine, and reabsorpted to the liver through the portal vein for reuse.
