protein part two
Proteins are polymer chains made of _________ linked together by _________.
-amino acids
-peptide bonds.
Functions protein:
Antibodies
Contractile Proteins
Enzymes
Hormonal Proteins
Structural Proteins
Storage Proteins
Transport Proteins
- are specialized proteins involved in defending the body from antigens (foreign invaders). They can travel through the blood stream and are utilized by the immune system to identify and
defend against bacteria, viruses, and other foreign intruders. One way antibodies counteract antigens is by immobilizing them so that they can be destroyed by white blood cells.
Antibodies
- are responsible for movement. These proteins are involved in muscle contraction and movement. Examples include actin and myosin
Contractile Proteins
Contractile Proteins - are responsible for movement. These proteins are involved in muscle contraction
and movement. Examples include ____ and _____
actin and myosin
- are proteins that facilitate biochemical reactions. They are often referred to as catalysts because they speed up chemical reactions. Examples include the enzymes lactase and pepsin.
Lactasebreaks down the sugar lactose found in milk. Pepsin is a digestive enzyme that works in the stomach to break down proteins in food.
Enzymes
Enzymes - are proteins that facilitate biochemical reactions. They are often referred to as catalysts because they speed up chemical reactions. Examples include the enzymes _______and _______.
________ breaks down the sugar lactose found in milk.
________ is a digestive enzyme that works in the stomach to break down proteins in food.
-lactase and pepsin
-Lactase
-Pepsin
- are messenger proteins which help to coordinate certain bodily activities. Examples include insulin, oxytocin, and somatotropin. Insulin regulates glucose metabolism by controlling the blood-sugar concentration. Oxytocin stimulates contractions in females during childbirth. Somatotropin is a growth hormone that stimulates protein production in muscle cells.
Hormonal Proteins
Hormonal Proteins - are messenger proteins which help to coordinate certain bodily activities.
Examples include _____,______, and ______.
______ regulates glucose metabolism by controlling the blood-sugar concentration.
_______ stimulates contractions in females during
childbirth.
_________ is a growth hormone that stimulates protein production in muscle cells.
-insulin, oxytocin, and somatotropin
-Insulin
-Oxytocin
-Somatotropin
- are fibrous and stringy and provide support. Examples include keratin, collagen, and elastin. Keratin strengthens protective coverings such as hair, quills, feathers, horns, and beaks. Collagensand elastinprovide support for connective tissues such as tendons and ligaments.
Structural Proteins
Structural Proteins - are fibrous and stringy and provide support. Examples include _____,______and _____.
_____ strengthens protective coverings such as hair, quills, feathers, horns, and beaks.
______ and _____ provide support for connective tissues such as tendons and ligaments.
keratin, collagen, and elastin.
Keratin
Collagens and elastin
- store amino acids. Examples include ovalbumin and casein. Ovalbuminis found in egg whites and caseinis a milk-based protein
Storage Proteins
Storage Proteins - store amino acids. Examples include _______ and _____.
__________ is found in egg whites and
_____ is a milk-based protein
-ovalbumin and casein
-Ovalbumin
-casein
- are carrier proteins which move molecules from one place to another around the body. Examples include hemoglobin and cytochromes. Hemoglobin transports oxygen through the blood. Cytochromes operate in the electron transport chain as electron carrier proteins.
Transport Proteins
Transport Proteins - are carrier proteins which move molecules from one place to another around the body. Examples include ________ and _________.
_________ transports oxygen through the blood.
_________ operate in the electron transport chain as electron carrier proteins.
-hemoglobin and cytochromes
-Hemoglobin
-Cytochromes
Protein is only used as fuel when ________ and ___ resources are low
carbohydrates and lipid
Proteins working together can allow movement within the body, such as ______________ and __________through the digestive system. It provides ______ and ______ to cells and tissues, controlling biochemical reactions and aiding the immune system.
-contraction of muscles
-movement of food
-structure and strength
Common Sources of Protein:
-Animal sources of protein include meats, dairy products, fish and eggs.
-Plant sources of protein include whole grains, pulses, legumes, soy, and nuts.
Amino acids are joined linearly by __________ which are formed by a reaction called dehydration. One molecule of
H2O is produced per peptide bond formed. The peptide bond has a partial double bond character and is rigid.
peptide bonds
Amino acids are joined linearly by peptide bonds which are formed by a reaction called ___________. One molecule of
H2O is produced per peptide bond formed. The peptide bond has a _________________ and is rigid.
-dehydration
-partial double bond character
2 amino acids joined by a peptide bond are called a dipeptide; many amino acids joined by peptide bonds are called polypeptides. By convention polypeptides are written from the N-terminal to the C-terminal. (Amino end to carboxyl end – remember A before C).
PEPTIDES
PEPTIDES
2 amino acids joined by a peptide bond are called a _______; many amino acids joined by peptide bonds are called
polypeptides. By convention polypeptides are written from the N-terminal to the C-terminal. (Amino end to carboxyl
end – remember A before C).
dipeptide
WHAT ARE AMINO ACIDS?
Any of large number of compounds found in living cells that contain carbon, oxygen, hydrogen, and nitrogen, and join together to form proteins.
Amino acids are molecules containing an
amino group(NH2)
carboxylic acid group(R-C=O-OH)
side-chain ( usually denoted as R)
There are _____________ in animal metabolism, but more occur in nature. Amino acids, the building blocks of proteins, have different side chains (denoted by the letter R) which are connected to a common backbone
20 amino acids
-are what determine the function of the protein that they make up.
Side chains (R)
_______,________,_________ have aromatic side chains.
Phenylalanine, Tyrosine and Tryptophan
________ and _________ contain sulfur
Cysteine and Methionine
_______ is an imino acid and forms a ring with its own backbone.
Proline
_________ has a polar side chain but it is still somewhat hydrophobic because of its aromaticity.
Charged side chains: Aspartate (-), Glutamate (-), Lysine (+), Arginine (+), Histidine (+) may take part in ionic interactions.
Tyrosine
___________ has an imidazole ring: it also offers buffering at physiologic pH to protein. Histidine is decarboxylated to histamine (a vasodilator)
Histidine
_______ and ________ contain hydroxyl groups which can form hydrogen bonds.
Serine and threonine
The sulfhydryl group is an important part of the active site of many enzymes.
In addition, two side chains may form a covalent disulfide bond which may join two different proteins or two different regions of the same protein.
Cysteine is formed by a disulfide bond joining of two cysteine residues. Keratin contains a lot of cysteine.
Cysteine
______ has an aliphatic side chain and a highly basic amino group at physiologic pH. Blood glycoproteins in diabetics contain glucose linked to lysine.
Lysine
________ has the largest side chain; it is hydrophobic with an aromatic ring. Tryptophan deficiency can cause Hartnup disease and Pellagra. (Trp > Niacin) Tryptophan is a precursor of Serotonin (5-NT). Tryptophan is hydroxylatedto 5-Hydroxytryptophan, and decarboxylated to 5 Hydroxytryptamine
Tryptophan
________ carries nitrogen from peripheral tissues to the liver.
Alanine
________ disrupts an α-helix in a polypeptide. Proline is usually the residue at the β-turn in β-pleated sheets (see secondary structure).
Proline
______ is the phosphorylation site of enzyme modification. Serine may be dehydrated and deaminated directly. In glycoproteins, serine is often linked to the carbohydrate group.
Serine
________ is deaminated by glutaminase resulting in the formation of ammonia. It is a major carrier of nitrogen to the liver (from peripheral tissues).
Glutamine
-Dipolar ions. Amino acids have a dipolar (+ and -) charge at neutral pH. From the protonated amino group (NH3+), and
ionized carboxyl group (COO-).
ZWITTERIONS
-Polarized light passing through an optically active sample is rotated to the left or right. The alpha-carbon of all amino
acids, except glycine, is bound to 4 different groups so it is called “chiral” and this makes amino acids optically active.
OPTICAL ACTIVITY
-Amino acids are in 2 configurations: “L” or “D.” In man, they are usually L-amino acids (remember, L-amino acids and D-sugars).
[L= levorotatory; rotation to the left]
[D = dextrorotatory; rotation to the right]
Higher organisms contain only L-amino acids in their proteins, but D-amino acids do occur in the peptidoglycans of bacterial cell walls.
CONFIGURATION
-Free amino acids are present through the body, in cells, blood, and the extracellular fluids. This pool is supplied
by the following sources:
AMINO ACID POOL
AMINO ACID POOL
Free amino acids are present through the body, in cells, blood, and the extracellular fluids. This pool is supplied by the following sources:
1) Amino acids derived from degradation of body protein
2) Amino acids derived from dietary protein
3) Synthesis of non-essential amino acids from simple intermediates of metabolism
Fates of amino acids:
1) for synthesis of body protein;
2) for synthesis of other nitrogen containing compounds ( e.g. porphyrins, creatine, neurotransmitters, purines and pyrimidines)
3) source of energy or for gluconeogenesis
4) source of fatty acids, CO2 and steroids
___ essential amino acids ( ___ conditionally essential)
___nonessential amino acids
8
1
11
– must be consumed in the diet
Essential
– can be synthesized in the body
Nonessential
– cannot be synthesized due to illness or lack of necessary precursors
Premature infants lack sufficient enzymes needed to create arginine
Conditionally essential
-Proteins, like other dietary macromolecules, are broken down by hydrolysis of specific peptide bonds and hence the enzymes involved are termed ‘peptidases’
Peptidases hydrolyze proteins
Peptidases hydrolyze proteins
Proteins, like other dietary macromolecules, are broken down by ____________________________ and hence the enzymes involved are termed ‘________’
-hydrolysis of specific peptide bonds
-‘peptidases’
These PEPTIDASES can either
a. Endopeptidases
b. Exopeptidases
- cleave internal peptide bonds
Endopeptidases
- cleave off one amino acid at a time from either the –COOH or –NH2 terminal of the polypeptide ( hence,they are subclassified into carboxypeptidases , and aminopeptidases)
Exopeptidases
Exopeptidases - cleave off one amino acid at a time from either the –COOH or –NH2 terminal of the polypeptide (hence,they are subclassified into ________________ and __________)
carboxypeptidases and aminopeptidases
The endopeptidases cleave the _____________ to smaller __________, which can be acted upon by the
exopeptidases to produce the __________ of protein digestion, amino acids, di- and tripeptides, which are then absorbed by the __________
-large polypeptides
-oligopeptides
-final products
-enterocytes
Peptidases are produced by three Different organs :
1. The stomach
2. The pancreas
3. The small intestine
The digestion of proteins begins in the ________, which secretes gastric juice, a unique solution containing ____________ and the proenzyme _________
-stomach
-hydrochloric acid
-pepsinogen
secreted by parietal cells of the stomach
Creates optimal pH for pepsin
Denaturates proteins
Kills most bacteria and other foreign cells
Hydrochloric acid
Hydrochloric acid:
-secreted by __________ of the stomach
-Creates optimal pH for pepsin
-Denaturates proteins
-Kills most bacteria and other foreign cells
parietal cells
-This acid-stable endopeptidase is secreted by the chief cells as an inactive zymogen (or proenzyme), pepsinogen
-In general, zymogens contain extra amino acids in their sequences, which prevent them from being catalytically active
-Pepsinogen is activated to Pepsin either by HCL, or autocatalytically by other Pepsin molecules that have already been activated
-Pepsin releases peptides and a few free amino acids from dietary proteins
Pepsin (active form)
Pepsin (active form):
This acid-stable endopeptidase is secreted by the ________ as an ___________ (or proenzyme), pepsinogen
In general, zymogens contain extra amino acids in their sequences, which prevent them from being catalytically active
Pepsinogen is activated to ______ either by HCL, or _____________ by other Pepsin molecules that have already been activated
Pepsin releases peptides and a few free amino acids from dietary proteins
-chief cells
-inactive zymogen
-Pepsin
-autocatalytically
On entering the small intestine, large polypeptides produced in the stomach by the action of pepsin are further cleaved to _________ and ___________ by a group of _______________
-oligopeptides
-amino acids
-pancreatic proteases
The release and activation of the pancreatic zymogens is mediated by the secretion of cholecystokinin and secretin,
two polypeptide hormones of the digestive tract
Release of zymogens
Release of zymogens:
The release and activation of the pancreatic zymogens is mediated by the secretion of _____________ and _________,
two polypeptide hormones of the digestive tract
cholecystokinin and secretin
Enteropeptidase, an enzyme synthesized by and present on the luminal surface of intestinal mucosal cells of the brush border membrane, converts the pancreatic zymogen trypsinogen to trypsin by removal of a hexapeptide from the
NH2-terminus of trypsinogen
Trypsin subsequently converts other trypsinogen molecules to trypsin
Enteropeptidase thus unleashes a cascade of proteolytic activity, because trypsin is the common activator of all the pancreatic zymogens
Activation of zymogens
Activation of zymogens:
_____________, an enzyme synthesized by and present on the luminal surface of intestinal mucosal cells of the brush border membrane, converts the pancreatic zymogen __________ to ______ by removal of a hexapeptide from the NH2-terminus of trypsinogen
______ subsequently converts other trypsinogen molecules to trypsin
Enteropeptidase thus unleashes a cascade of proteolytic activity, because trypsin is the ______________ of all the pancreatic zymogens
-Enteropeptidase
-trypsinogen
-trypsin
-Trypsin
-common activator
Each of these enzymes has a different specificity for the amino acids R groups adjacent to the susceptible peptide bond.
Specificity
Specificity:
Each of these enzymes has a different specificity for the amino acids ___________ adjacent to the susceptible peptide
bond.
R groups
The luminal surface of the intestine contains ______________ that repeatedly cleaves the _____________ residue from
oligopeptides to produce free amino acids and smaller peptides
-Aminopeptidase
-N-terminal
Amino Acid Absorption
Free Amino acids and dipeptides are absorbed by the intestinal epithelial cells in which the dipeptides are hydrolyzed to amino acids in the cytosol before they enter the portal system. Thus, only free amino acids are found in the portal vein after a meal containing protein.
-Amino acids are transported to the ___ from the _______ via the portal vein
-In the liver, amino acids are:
to liver from intestines
-Used to synthesize new proteins
-Converted to energy, glucose, or fat
-Released to the bloodstream and transported to cells throughout the body
Best Sources of Protein
-Proteins are abundant in:
-Dairy foods
-Meats
-Poultry
-Meat alternatives such as dried beans, peanut butter, nuts, and soy
An essential amino acid which an organism ____________ because it is necessary for nutrition and __________________
-needs to ingest
-cannot be synthesized in the body
ESSENTIAL AMINO ACIDS
1. Phenylalanine
2. Valine
3. Tryptophan
4. Threonine
5. Isoleucine
6. Methionine
7. Leucine
8. Lysine
RELATIVELY ESSENTIAL AMINO ACIDS
1. Histidine
2. Arginine
PVT:
1. PHENYLALANINE
2. VALINE
3. THREONINE
TIM:
1.TRYPTOPHAN
2.ISOLEUCINE
3.METHIONINE
HALL:
1.HISTIDINE
2.ARGININE
3.LEUCINE
4.LYSINE
Amino acids that can be synthesized in sufficient amounts in humans or that may be made from precursors
NON-ESSENTIAL AMINO ACIDS
The relative ability of a protein source to provide all the essential amino acids. Animal sources have the highest biologic value while individual vegetable sources are lower (because they lack enough of one or more of the essential amino acids). However, combined different vegetable sources can result in meals of high biologic value that provide enough of all the essential amino acids.
BIOLOGIC VALUE
Nitrogen balance is a measure of the protein status of the
body. Most of the nitrogen in the body is from consumption
of amino acids. When not enough protein is ingested, the body breaks down its own protein and excretes more nitrogen than what is taken in; the body is in negative nitrogen balance. On the other hand, growing children with adequate protein intake will store more nitrogen in their new muscles than they excrete and will be in positive nitrogen balance.
NITROGEN BALANCE
STRUCTURE OF PROTEINS
1. PRIMARY STRUCTURE
2. SECONDARY STRUCTURE
3. TERTIARY STRUCTURE
4. QUATERNARY STRUCTURE
Sequence of amino acids in polypeptide chain, i.e.:
N-leu-met-glu-val-ala-leu-gly-gly-phe-C
The primary structure is important for deciding the higher structure of proteins. It is simply the amino acid sequence. It also determines the location of disulfide bonds.
PRIMARY STRUCTURE
If present, it is the result of hydrogen bonding between the C=O of one peptide bond and the N-H of another peptide bond. This hydrogen bonding produces regularly repeated structures, the most important of which are the α-helix and β-pleated sheets. However, these structures are not present in all polypeptides.
SECONDARY STRUCTURE
The ______ is stabilized by hydrogen bonds. Hydrogen bonds are between a carboxyl and amino group, and occur four amino acids away in the same polypeptide chain (actually 3.6 amino acids per turn). Hydrogen bonds are parallel to the axis of the helix, and the R-groups come off the sides. The α-helix is a rod-like structure and in man is usually a right-handed helix. The side chains point away from the center of the rod. An α-helix is disrupted by Proline.Regions with many charged or bulky side chains (i.e., tryptophan) can also disrupt the helix.
α-Helix
There are two types of _______ Sheets. Parallel sheets and Anti-parallel sheets. Hydrogen bonds occur between 2 different polypeptide chains or 2 regions of the same chain.
β-Pleated
There are two types of β-Pleated Sheets. __________ and ____________ sheets. Hydrogen bonds occur between 2 different polypeptide chains or 2 regions of the same chain.
Parallel sheets and Anti-parallel sheets
The overall 3-dimensional shape of protein. Most proteins are globular. Some proteins are fibrous, like collagen.
The tertiary structure is the result of the combination of the primary structure, secondary structure and the interactions
between the different side chains, i.e.:
Covalent disulfide bonds between 2 cysteine. This anchors two chains and is found in proteins designated for export.
Hydrophobic side chains are oriented to the inside of globular proteins and away from water.
Hydrogen bonds between the side chains of threonine and serine.
Ionic interactions between the charged side chains.
TERTIARY STRUCTURE
Some proteins are made up of multiple subunits, each ofwhich contain a single polypeptide chain. These subunits join to form a single protein held together by the same forces that maintain tertiary structure. The number of subunits and their spatial arrangement comprise quaternary structure. In general,
several polypeptides make a protein functional.
Examples include: Hemoglobin and Myoglobin.
QUATERNARY STRUCTURE
____________ is a globular protein made up of 4 polypeptide chains: 2 alpha and 2 beta chains
A subunit structure in adults: α2β2. Each chain contains a heme molecule. A heme molecule contains one iron
atom molecule (O2). Therefore, since there are four chains in a heme molecule, a total of 4 oxygens can be carried by
each hemoglobin. The major Hb at birth: HbF, with subunit structure α2y2. Hemoglobin F binds oxygen tighter than HbA
does. Hemoglobin can transport CO2.
Hemoglobin
Decreased affinity of hemoglobin for oxygen results from:
1. Increased levels of CO2
2. increased levels of 2,3-DPG (diphosphoglycerate) in RBC’s,
3. acidosis or lowered pH (the Bohr effect), and
4. increased temperature (all shift the oxygen-dissociation curve to the right.
concentration may be increased in patients with diabetes mellitus. The amount of glycosylated hemoglobin depends on the glucose level in the blood; a normal value is between 3 to 9% of the Hb (α2β2-glucose). The HbA1c concentration reflects the blood glucose level for the previous few months, and is helpful in assessing if the patient is compliant with insulin treatment and diabetes control.
Glycosylated Hb: HbA1c
results from substitution of valine for glutamate at position 6 on the β-chains in hemoglobin (HbS). Valine has a neutral charge, and it replaces glutamate (-1). The sickle shape favors the deoxy form and this leads to a crisis.
HbC is another hemoglobin variant that has a modified β-chain at position 6, but in HbC, lysine (+1 charge) replaces glutamate.
Sickle cell anemia