‫پروتئین ها‬
‫‪1‬‬
‫اسیدهای آمینه و پروتئین ها‬
.‫پلیمرهای زیستی که واحد سازنده آنها اسیدهای آمینه است‬
.‫ترکیبات آلی که در ساختمان آنها حداقل یک عامل کربوکسیل و یک عامل آمین وجود دارد‬
•
•
.‫ اسید آمینه حاصل می شود‬20 ‫• از هیدرولیز پروتئینهای بدن حدود‬
Proteins are associated with all forms of life, and
much of the effort to determine how life
began has centered on how proteins were first
produced
The largest source of protein in higher animals
resides in muscle
Protein on average is 16% by weight N
2
Proteins are polymer chains made of amino acids linked
together by peptide bonds. Proteins and carbohydrates
contain 4 kcal per gram as opposed to lipids which
contain 9 kcal per gram.
Amino acids can be divided into either essential amino
acids or non-essential amino acids. The essential amino
acids, which must be obtained from food sources, are
leucine, isoleucine, valine, lysine, threonine, tryptophan,
methionine, phenylalanine and histidine. On the other
hand, non-essential amino acids can be made by the body
from other amino acids. The non-essential amino acids are
arginine, alanine, asparagine, aspartic acid, cysteine,
glutamine, glutamic acid, glycine, proline, serine, and
tyrosine
3
.
‫ساختار اسیدهای‬
‫آمینه‬
‫در ساختار اسیدهای آمینه حداقل یک عامل‬‫کربوکسیل و یک عامل آمین وجود دارد‪.‬‬
‫‪ -‬اگر عامل کربوکسیل و عامل آمین بر روی‬‫اولین کربن فرار گرفته باشد آن را آلفا آمینو‬
‫اسید می گویند‪.‬‬
‫‪ -‬بقیه مولکول اسید آمینه را ریشه یا ‪R‬‬‫می نامند‪.‬‬
‫‪ -‬کربوکسیل اسیدهای آمینه می تواند با از‬‫دست دادن پروتون به صورت یون ‪ coo-‬و‬
‫عامل آمین آنها با گرفتن پروتون به صورت‬
‫یون ‪ NH3+‬درایند‪.‬‬
‫‪ -‬بنابراین اسیدهای آمینه می توانند به حالت‬‫بافری دربیایند‪.‬‬
‫‪4‬‬
The Chemist’s View of Proteins
5
‫انواع اسیدهای آمینه بر اساس گروه ‪R‬‬
‫‪6‬‬
‫پروتئین ها‬
‫• پروتئین ها مهمترین دسته مواد شیمیایی در بدن هستند‪.‬‬
‫• پروتئین ها از اتصال اسیدهای آمینه با پیوند پپتیدی تشکیل‬
‫می شود‪ .‬پیوند پپتیدی از اتصال گروه کربوکسیل یک اسید‬
‫آمینه با گروه آمین اسید آمینه دیگر به وجود می آید‪.‬‬
‫‪7‬‬
The Chemist’s View of Proteins
8
‫دو اسید امینه = دی پپتید‬‫‪ 2‬تا ‪ 10‬اسید آمینه = الیگوپپتید‬‫ ‪ 10‬تا ‪ 50‬اسید امینه = پلی پپتید‬‫ بیش از ‪ 50‬اسید آمینه و وزن‬‫مولکولی بیش از ‪ = 50‬پروتئین‬
‫نکته‪ :‬در تشکیل پیوند ریشه ‪R‬‬‫دخالت ندارد‪.‬‬
‫هر زنجیره یک انتهای آمینی و‬‫یک انتهای آزاد دارد‪.‬‬
‫‪9‬‬
‫ساختمان پروتئین ها‬
‫• اختالف پروتئین ها در ‪ :‬تعداد اسیدهای آمینه‪ ،‬ترتیب قرار‬
‫گرفتن آنها و ساختمان فضایی آنها است‬
‫‪10‬‬
‫چهار سطح ساختمان‬
‫پروتئین‬
‫ساختمان دوم‪:‬زنجیره پلی پپتیدی یک‬
‫محور فرضی پیچیده و ساختمان‬
‫فضایی (هلیکس)پیدا می کند‪.‬پیوند‬
‫هیدروژنی بین ‪ co‬از یک پیوند پپتیدی‬
‫و ‪ NH‬از پیوند پپتیدی دیگر سبب‬
‫ایجاد و استحکام ساختمان دوم می‬
‫شود‪.‬مثل‪ :‬کالژن‬
‫ساختمان سوم‪ :‬طویل شدن زنجیره‬
‫پپتیدی و وجود اسید آمینه پرولین سبب‬
‫خمیده شدن و تشکیل ساختمان کروی‬
‫می شود‪.‬میوگلوبین‬
‫ساختمان چهارم‪:‬انصال دو یا چند‬
‫زنجیره پلی پپتیدی با ساختمان سوم به‬
‫یکدیگر‪ :‬هموگلوبین‬
‫‪11‬‬
‫طبقه بندی پروتئینها بر اساس عملکرد زیستی آنها‬
‫نوع‬
‫آنزیمها‪ ،‬کاتالیز کردن واکنشهای بیولوژیکی‬
‫انتقال دهنده و ذخیره کننده‬
‫حرکت‬
‫پروتئین های ایمنی‬
‫عملکرد ایمنی درون سلول‬
‫‪Example:‬‬
‫‪ß-galactosidase‬‬
‫‪Hemoglobin‬‬
‫‪Actin‬‬
‫‪And Myosin in muscles‬‬
‫‪Immunoglobulins‬‬
‫)‪(antibodies‬‬
‫‪Transeription Factors‬‬
‫هورمونها‬
‫‪Insulin‬‬
‫‪Estrogen‬‬
‫ساختاری‬
‫‪Collagen‬‬
‫‪12‬‬
TURNOVER OF PROTEINS IN THE BODY
proteins in the body are not static. Just as every protein is
synthesized, it is also degraded. The concept that proteins are
continually made and degraded in the body at different rates
We now know that the rate of turnover of proteins in the body
spans a broad range and that the rate of turnover of individual
proteins tends to follow their function in the body; that is, those
proteins whose concentrations need to be regulated (e.g., enzymes)
or that act as signals (e.g., peptide hormones) have relatively high
rates of synthesis and degradation as a means of regulating
concentrations. Conversely, structural proteins such as collagen
and myofibrillar proteins or secreted plasma proteins have
relatively long lifetimes
13
However, there must overall be a
balance between synthesis and
breakdown of proteins. Balance in
healthy adults who are neither
gaining or losing weight will be
that the amount of N consumed as
protein in the diet will match the
amount of N lost in urine, feces,
and other routes
14
‫دناتوره شدن پروتئین ها چیست؟‬
‫• به هم خوردن شکل فضایی پروتئین‬
‫• عوامل‪ :‬حرارت‪ ،‬اشعه‪ ،‬اسید و باز‪،‬‬
‫حاللها‪ ،‬شوینده ها‬
‫‪15‬‬
Roles of Proteins
• Growth and maintenance
– Building blocks for most body structures
• Collagen
– Replacement of dead or damaged cells
• Enzymes
– Break down, build up, and transform substances
– Catalysts
16
Roles of Proteins
• Hormones
– Messenger molecules
– Transported in blood to target tissues
• Regulators of fluid balance
– Edema
• Acid-base regulators
– Attract hydrogen ions
• Transporters – specificity
17
Roles of Proteins
• Antibodies
– Defend body against disease
– Specificity
• Immunity – memory
• Energy and glucose
– Starvation and insufficient carbohydrate intake
• Other roles
18
Preview of Protein Metabolism
 Protein turnover & amino acid pool
 Continual production and destruction
 Amino acid pool pattern is fairly constant
 Used for protein production
 Used for energy – if stripped of nitrogen
 Nitrogen balance
 Zero nitrogen balance or equilibrium
 Positive and negative nitrogen balance
19
Preview of Protein Metabolism
• Making other compounds
– Neurotransmitters
– Melanin
– Thyroxin
– Niacin
• Energy and glucose
– Wasting of lean body tissue
• Adequate intake of carbohydrates and fats
20
Preview of Protein Metabolism
• Making fat
– Energy and protein exceed needs
– Carbohydrate intake is adequate
– Can contribute to weight gain
• Deaminating amino acids
– Stripped of nitrogen-containing amino group
• Ammonia
• Keto acid
21
Preview of Protein Metabolism
• Make proteins & nonessential amino acids
– Breakdown of proteins
– Keto-acids
– Liver cells and nonessential amino acids
• Converting ammonia to urea
– Liver – ammonia and carbon dioxide
– Dietary protein
22
‫سوخت اسیدهای آمینه‬
‫•‬
‫•‬
‫•‬
‫•‬
‫از دست دادن آمین (ترانس آمیناسیون و دز آمیناسیون) و‬
‫تبدیل به کتواسید و ورود به سیکل کربس‬
‫اسیدامینه های گلیکوژنیک‬
‫اسیدامینه های کتوژنیک‬
‫سرنوشت عامل آمین‪ -1 :‬آمونیاک(انتقال با گلوتامین به کبد‬
‫و تبدیل به اسیدگلوتامیک و تبدیل به اوره و دفع ‪ ،‬کلیه و‬
‫دفع به شکل کلرور آمونیوم در کلیه)‬
‫‪23‬‬
24
AMINO ACID CATABOLISM
• The other biological fuels discussed
(carbohydrates & fats) contain only the elements
carbon, hydrogen and oxygen. Amino acids
contain nitrogen as well. The first step in amino
acid catabolism is the removal of the nitrogen (the
amino group).
25
DEAMINATION
The removal of the amino groups of all twenty amino acids
begins with the transfer of amino groups to just one amino acid glutamic acid (or glutamate ion). This is catalysed by
transaminase enzymes which transfer the amino group from
amino acids to a compound called alpha-ketoglutarate. The
product is an alpha-keto acid formed from the amino acid and
glutamate (formed from the addition of the amino group to alphaketoglutarate.
Once the amino groups have all been "collected" in the form of
the one amino acid, glutamate, this amino acid has its amino
group removed (termed "oxidative deamination"). This reaction
reforms alpha-ketoglutarate with the other product being
ammonia (NH4 +).
26
27
28
AMMONIA AND UREA
Ammonia is toxic to the nervous
system and its accumulation rapidly
causes death. Therefore it must be
detoxified to a form which can be
readily removed from the body.
Ammonia is converted to urea, which
is water soluble and is readily excreted
via the kidneys in urine.
29
AMINO ACID CARBON SKELETONS
The remainder of the amino acid is referred to as the "carbon
skeleton". Depending on the particular amino acid being
catabolised, its carbon skeleton will be converted to :
acetyl CoA
Those carbon skeletons which end up as acetyl CoA are
committed to energy production. They will either be
immediately oxidised via the citric acid cycle or they may be
converted to ketone bodies. Because the amino acids whose
carbon skeletons yield acetyl CoA are potentially a source of
ketone bodies they are referred to as ketogenic amino acids.
30
or pyruvate or a citric acid cycle intermediate
The carbon skeletons which end up as either
pyruvate or a citric acid cycle intermediate may
be used for energy production or they may be
used to synthesis glucose by the pathway known
as gluconeogenesis. Because the amino acids
whose carbon skeletons yield pyruvate or a citric
acid cycle intermediate are potentially a source
of glucose they are referred to as glucogenic
amino acids.
31
Loss of more than about 30% of body
protein results in reductions in muscle
strength for breathing, immune
function, and organ function and,
ultimately, in death. Hence, the body
must adapt to fasting by conserving
protein, as is seen by a dramatic
decrease in N excretion within the first
week of onset of starvation
32
‫گلوکونئو ژنزوکتو ژنز‬
‫•‬
‫•‬
‫•‬
‫•‬
‫•‬
‫اسکلت کربنی اسیدهای آمینه می توانند به عنوان منبع سوختی در‬
‫متابولیسم اکسیداتیو مورد استفاده قرار گیرندواز نقاط مختلفی وارد‬
‫مسیر اکسیداتیو شوند‪.‬همینطور برای سنتز گلوکز یا اجسام کتونی‬
‫براساس سرنوشت اسیدهای آمینه به اسید های آمینه گلوکوژنیک‬
‫وکتوژنیک طبقه بندی می شوند‪.‬‬
‫همه اسیدهای آمینه به جز لوسین و لیزین که به استیل‪-‬کو‪A‬تبدیل‬
‫میشوند میتوانند در فرایند گلوکونئو ژنز شرکت کنند‪.‬‬
‫گلوکونئوژنز به طور عمده در کبد وتا حدی در کلیه ها رخ می دهد‪.‬‬
‫آالنین وگلوتامین اسید های آمینه کلیدی در انتقال نیتروژن بین بافت‬
‫ها به شمار می روند‪.‬‬
‫‪33‬‬
Protein Metabolism
34
Nitrogen Pool
35
Urea Cycle
36
Protein Quality
• Two factors
– Digestibility
• Other foods consumed
• Animal vs. plant proteins
– Amino acid composition
• Essential amino acid consumption
• Nitrogen-containing amino groups
• Limiting amino acid
37
Protein functions in body
Protein is a nutrient needed by the human body for growth
and maintenance. Aside from water, protein is the most
abundant molecule in the body. Protein is found in all
cells of the body and is the major structural component of
all cells in the body, especially muscle. This also includes
body organs, hair and skin. Proteins also are utilized in
membranes, such as glycoproteins. When broken down
into amino acids, they are used as precursors to nucleic
acid and vitamins. Hormones and enzymes are also
formed from amino acids in which they help regulate
metabolism, support the immune system and other body
functions. Finally, protein is needed to form blood cells
38
Sources
There are many different sources of
protein including whole protein foods
(such as milk, meat, fish, egg, and
vegetables)
39
Protein quality
Different proteins have different levels of biological availability
(BA) to the human body. Many methods have been introduced to
measure protein utilization and retention rates in humans. They
include biological value, net protein utilization, and PDCAAS
(Protein Digestibility Corrected Amino Acids Score) which was
developed by the FDA as an improvement over the Protein
Efficiency Ratio (PER) method. These methods examine which
proteins are most efficiently used by the body. The PDCAAS
rating is a fairly recent evaluation method; it was adopted by the
US Food and Drug Administration (FDA) and the Food and
Agricultural Organization of the United Nations/World Health
Organization (FAO/WHO) in 1993 as "the preferred 'best'"
method to determine protein quality. These organizations have
suggested that other methods for evaluating the quality of protein
are inferior
40
Digestion
Most proteins are decomposed to single amino acids in digestion.
Digestion typically begins in the stomach when pepsinogen is converted to pepsin by
the action of hydrochloric acid, and continued by trypsin and chymotrypsin in the
intestine Before the absorption in the small intestine, most proteins are already
reduced to single amino acid or peptides of several amino acids Most of peptides
longer than 4 amino acids are not absorbed Absorption into the intestinal absorptive
cells is not the end.There most of peptides are broken into single AA
Absorption of the amino acids and their derivatives into which dietary protein is
degraded is done by the gastrointestinal tract. The absorption rates of individual
amino acids are highly dependent on the protein source; for example, the
digestibilities of many amino acids in humans, the difference between soy and milk
proteins and between individual milk proteins, beta-lactoglobulin and casein. For
milk proteins, about 50% of the ingested protein is absorbed between the stomach
and the jejunum and 90% is absorbed by the time the digested food reaches the
ileum. Biological value (BV) is a measure of the proportion of absorbed protein from
a food which becomes incorporated into the proteins of the organism's body
41
Newborn
Newborns of mammals are exceptional in
protein digestion and assimilation in that
they can absorb intact proteins at the small
intestine. This enables passive immunity
from milk
42
Dietary requirements
The amount of protein required in a person's diet is
determined in large part by overall energy intake, the
body's need for nitrogen and essential amino acids,
body weight and composition, rate of growth in the
individual, physical activity level, individual's energy
and carbohydrate intake, as well as the presence of
illness or injury. Physical activity and exertion as
well as enhanced muscular mass increase the need
for protein. Requirements are also greater during
childhood for growth and development, during
pregnancy or when breast-feeding in order to nourish
a baby, or when the body needs to recover from
malnutrition or trauma or after an operation
43
If enough energy is not taken in through
diet, as in the process of starvation, the
body will use protein from the muscle mass
to meet its energy needs, leading to muscle
wasting over time. If the individual does
not consume adequate protein in nutrition,
then muscle will also waste as more vital
cellular processes (e.g. respiration
enzymes, blood cells) recycle muscle
protein for their own requirements
44
Recommended Dietary Allowance for Protein
Grams of protein
needed each day
Children ages 1 – 3
13
Children ages 4 – 8
19
Children ages 9 – 13
34
Girls ages 14 – 18
46
Boys ages 14 – 18
52
Women ages 19 – 70+
46
Men ages 19 – 70+
56
45
Excessconsumption
When a high dietary protein intake is consumed, there is
an increase in urea excretion, which suggests that amino
acid oxidation is increased. As a result, oxidation is
facilitated, and the amino group of the amino acid is
excreted to the liver. This process suggests that excess
protein consumption results in protein oxidation and that
the protein is excreted. The body is unable to store excess
protein. Protein is digested into amino acids, which enter
the bloodstream. Excess amino acids are converted to
other usable molecules by the liver in a process called
deamination. Deamination converts nitrogen from the
amino acid into ammonia, which is converted by the liver
into urea in the urea cycle.
46
Excretion of urea is performed by the kidneys. These
organs can normally cope with any extra workload, but,
if a kidney disease occurs, a decrease in protein will
often be prescribed. Furthermore, as noted, protein
provides the body with 4 calories per gram, and when
there is excess protein intake, the body will utilize as
much of it for energy as possible. After that stage, the
body will produce fat from the excess protein, turning it
into fat cells. On the other hand, if people do not eat
enough calories, body protein and protein from the food
will be utilized for energy. This is not ideal as the main
function of protein is to maintain Muscle Mass.
47
Finally, when food protein intake is
periodically high or low, the body tries
to keep protein levels at an equilibrium
by using the “labile protein reserve",
which serves as a short-term protein
store to be used for emergencies or
daily variations in protein intake.
However, that reserve is not utilized as
longer-term storage for future needs.
48
Many researchers have also found that excessive
intake of protein increases calcium excretion in
urine. It has been thought that this occurs to
maintain the pH imbalance from the oxidation of
sulfur amino acids.
Another issue arising from overconsumption of
protein is a higher risk of kidney stone formation
from calcium in the renal circulatory system. It has
been found that high animal protein intake in
healthy individuals increases the probability of
forming kidney stones by 250 percent
49
Food allergies
Specific proteins found in certain food items are
often the cause of allergies and allergic reactions.
This is because the structure of each form of
protein is slightly different; some may trigger a
response from the immune system while others
remain harmless. Many people are allergic to
casein, the protein in milk; gluten, the protein in
wheat and other grains; the particular proteins
found in peanuts; or those in shellfish or other
seafoods. Food allergies should not be confused
with food intolerance
50
Deficiency in developing countries
Protein deficiency is a serious cause of ill health and death in
developing countries. Protein deficiency plays a part in the disease
kwashiorkor. Famine, overpopulation and other factors can increase
rates of malnutrition and protein deficiency. Protein deficiency can
lead to reduced intelligence or mental retardation
In countries that suffer from widespread protein deficiency, food is
generally full of plant fibers, which makes adequate energy and
protein consumption very difficult. Protein deficiency is generally
caused by lack of total food energy, making it an issue of not getting
food in total. Symptoms of kwashiorkor include apathy, diarrhea,
inactivity, failure to grow, flaky skin, fatty liver, and edema of the
belly and legs. This edema is explained by the normal functioning of
proteins in fluid balance and lipoprotein transport
51