2. OVERALL METABOLISM OF PROTEINS
All proteins in the body are continuously degraded
(metabolized) and newly synthesized
Free AA from food, tissue proteins and non-
essential AA from synthesis make AA pool
AA pool is used for:
1. New body proteins
2.Specialized products (amines, porphyrines,
Nucleic Acid bases ...)
3. Catabolic proceses (energy gain)
3. In healthy, well
fed individuals,
the input to the
amino acid pool
is balanced by
the output, that
is, the amount
of amino acids
contained in the
pool is constant.
The amino acid
pool is said to
be in a steady
state.
The amino acid pool is a grand mixture of amino acids
available in the cell derived from dietary sources or the
degradation of protein. Since proteins and amino acids
are not stored in the body, there is a constant turnover of
protein.
4. 4
AA pool
Definition: AA POOL It includes the free
AAs distributed throughout the body
~ 80 % in muscles ~ 10 % in liver
~ 5 % in kidney ~ 5 % in blood
In contrast to the amount of protein in the body
(about 12 Kg in 70 Kg man), the AA. pool is small
(only 100 gm. 50% of these AAs are in the form of
glutamate & glutamine (Why?). )
AA pool is not reserve !!
There is no specific protein reserve in human body in contrast to
saccharides (liver glycogen) and lipids (adip. tissue) !!
5. Amino acid pool
Diatery proteins
Non essential a.a.s
synthesized in the body
Tissue proteins
Catabolism(Deamination)
Anabolism
a.a.s
Synthesis of
Proteins Other nitrogenous compounds
►Tissue proteins
►Plasma proteins
►Enzymes
►Some hormones
►Milk
►Aminosugars
►Nitrogenous bases
of phospholipids
►Purines & pyrimidines
►Neurotransmitters
►Niacin
►Creatine
►Heme
Fate of deamination products
α- keto acid Ammonia
glucose Ketone bodies CO2+H2O
+ENERGY
Krebs
cycle
Synthetic
pathway
Catabolic
pathway
Urea glutamine Excreted
in urine
Non essential
a.a.synthesis
SOURCES & FATE OF THE AA. POOL
6. Some protein is constantly being synthesized while
other protein is being degraded. For example, liver and
plasma proteins have a half-life of 180 days or more,
while enzymes and hormones may be recycled in a
matter of minutes or hours.
7. Nitrogen Balance
nitrogen balance is achieved by a healthy person when
the dietary intake is balanced by the excretion of urea
wastes. If nitrogen excretion is greater than the
nitrogen content of the diet, the person is said to be in
negative nitrogen balance. This is usually interpreted
as an indication of tissue destruction.
If the nitrogen excretion is less than the content of the
diet, a positive nitrogen balance indicates the
formation of protein.
8. Human proteins have very different lifetimes. Total
body protein is about 12 kg, but about 25% of this is
collagen, which is metabolically inert.
A typical muscle protein might survive for three weeks,
but many liver enzymes turn over in a couple of days.
Some regulatory enzymes have half-lives measured in
hours or minutes. The majority of the amino acids
released during protein degradation are promptly re-
incorporated into fresh proteins.
Protein turnover
9. Protein turnover
The recommended minimal protein intake required to
achieve nitrogen balance in healthy adults is about 50g
per day, although in developed countries many people
may eat double this amount. This compares with an
average daily protein turnover of about 250g per day.
Most of the ingested protein is ultimately oxidized to
provide energy, and the surplus nitrogen is excreted, a
little as ammonia but mostly as urea.
11. Soluble intracellular
proteins are tagged for
destruction by attaching
ubiquitin, a low molecular
weight protein marker.
They are then degraded in
proteasomes to short
peptides
The ATP-dependent ubiquitin-
proteasome system of the
cytosol
12. The ATP-independent degradative enzyme
system of the lysosomes. Proteasomes degrade
mainly endogenous proteins, that is, proteins that
were synthesized within the cell. Lysosomal
enzymes (acid hydrolases, degrade primarily
extracellular proteins, such as plasma proteins
that are taken into the cell by endocytosis, and
cell-surface membrane proteins that are used in
receptor-mediated endocytosis.
14. Angelman Syndrome
Angelman syndrome is a
genetic disorder that
causes developmental
disabilities and
neurological problems,
such as difficulty speaking,
balancing and walking,
and, in some cases,
seizures. Frequent smiles
and outbursts of laughter
are common for people
with Angelman syndrome,
and many have happy,
excitable personalities.
15. People with Angelman
syndrome tend to live a
normal life span. But
they may become less
excitable and develop
sleep problems that may
improve with age.
Angelman syndrome usually isn't detected until parents
begin to notice developmental delays when a baby is
about 6 to 12 months old. Seizures often begin when a
child is between 2 and 3 years old. Treatment focuses on
managing medical and developmental issues.
18. Transport of AA into cells
Amino acid uptake from the gut lumen into
enterocytes is driven by the sodium gradient.
There is a relatively high sodium concentration in the
gut and a low concentration in the enterocytes, as a
result of the sodium pump in the basolateral
membrane.
19. The concentration of free amino acids in the
extracellular fluids is significantly lower than that
within the cells of the body.
This concentration gradient is maintained because
active transport systems, driven by the hydrolysis of
ATP, are required for movement of amino acids from
the extracellular space into cells.
20. At least seven different transport systems are known that
have overlapping specificities for different amino acids
The small intestine and the proximal tubule of the kidney
have common transport systems for amino acid uptake;
therefore, a defect in any one of these systems results in
an inability to absorb particular amino acids into the gut
and into the kidney tubules
21. For example, one system is responsible for the uptake
of cystine and the dibasic amino acids, ornithine,
arginine, and lysine (represented as “COAL”).
In the inherited disorder cystinuria, this carrier
system is defective, and all four amino acids appear in
the urine
22. CYSTINURIA
occurs at a frequency of 1 in 7,000 individuals, making
it one of the most common inherited diseases, and the
most common genetic error of amino acid transport.
The disease expresses itself clinically by the
precipitation of cystine to form kidney stones
(calculi), which can block the urinary tract.
Oral hydration is an important part of treatment for
this disorder.
23. HARTNUP DISEASE
Is also referred to as Hartnup disorder. It’s a hereditary
metabolic disorder. It makes it difficult for body to
absorb certain amino acids from intestine and reabsorb
them from kidneys.
In most people, body absorbs specific amino acids into
intestines and then reabsorbs them in kidneys. If you
have Hartnup disease, you can’t properly absorb certain
amino acids from small intestine. Also they can’t be
reabsorbed from kidneys. As a result, an excessive
amount of amino acids exits from body through
urination.
24. As a result of excessive loss of amino acids from body
through urination. This leaves the body with an
insufficient amount of these amino acids.
Without enough tryptophan, body can’t produce
enough niacin. A niacin deficiency can cause to develop
Pellagra like symptoms which include dermatitis( a sun-
sensitive rash) diarrhea and dementia.
25. Entry of Amino acid in cell
The sodium-amino acid carrier system involves the
uptake by the cell of a sodium ion and an amino acid
by the same carrier protein (cotransporter) on the
luminal surface of the intestine. There are at least
seven different carrier proteins that transport different
groups of amino acids. The sodium ion is pumped
from the cell on the serosal side (across the basolateral
membrane) by the Na+ - K+ ATPase in exchange for
K+, providing the driving force for transport of amino
acids into the intestinal epithelial cells.
30. The amino acid travels down its concentration
gradient into the portal blood, crossing the basal
epithelial membrane via a facilitated transporter.
Genetic defects in genes encoding the carrier proteins
can result in abnormal amino acid uptake from the
intestines, leading to amino acid deficiency. (e.g.
Hartnup disease, in which neutral amino acids are
neither transported normally across the intestinal
epithelium nor reabsorbed normally from the kidney
glomerular filtrate, leading to hyperaminoacidurea;
hypercystinurea, high urine cysteine, occurs with a
frequency of approximately 1 per 7000 live births
worldwide and may cause renal caliculi - kidney
stones).
31. Amino acids enter cells from the blood principally by
Na+-dependent cotransporters and, to a lesser extent,
by facilitated transporters. The Na+-dependent
transport in liver, muscle, and other tissues allows
these cells to concentrate amino acids from blood.
These transport proteins are encoded by different
genes and have different specificities than those
encoded by the genes specifying the luminal
membrane amino acid transporters of the intestinal
epithelia. They also differ somewhat between tissues
(e.g., the transport system for glutamine uptake present
in liver is either not present in other tissues or is
present as an isoform with different properties).
