Chem 45 Biochemistry: Stoker chapter 26 Protein Metabolism

Chapter 26
Table of Contents
Copyright © Cengage Learning. All rights reserved 2
26.1 Protein Digestion and Absorption
26.2 Amino Acid Utilization
26.3 Transamination and Oxidative Deamination
26.4 The Urea Cycle
26.5 Amino Acid Carbon Skeletons
26.6 Amino Acid Biosynthesis
26.7 Hemoglobin Catabolism
26.8 Interrelationships Among Metabolic Pathways
26.9B-Vitamins and Protein Metabolism

Section 26.2
Amino Acid Utilization
Nitrogen Balance
• The state that results when the amount of nitrogen taken into the
human body as protein equals the amount of nitrogen excreted from
the body in waste materials.
• Two types of nitrogen imbalance can occur in human body.
– Negative nitrogen imbalance: Protein degradation exceeds
protein synthesis
• Amount of nitrogen in urine exceeds nitrogen consumed
• Results in tissue wasting
– Positive nitrogen imbalance: Rate of protein synthesis
(anabolism) is more than protein degradation (catabolism)
• Results in large amounts of tissue synthesis
• During growth, pregnancy, etc.

Protein Digestion and Absorption
Section 26.1
• Protein digestion (denaturation and hydrolysis) starts in the stomach:
– Dietary protein in stomach promotes release of Gastrin hormone which promotes secretion
of pepsinogen and HCl; HCl in stomach has 3 functions:
• Gastric acidity denatures protein thereby exposing peptide bonds
• Gastric acidity (pH of 1.5-2.0) kills most bacteria
• Activates pepsinogen (inactive) to pepsin (active)
– Enzyme pepsin hydrolyzes about 10% peptide bonds
• Large polypeptide chains pass from stomach into small intestine:
– Passage of acidified protein promotes secretion of “Secretin” hormone which stimulates:
• Bicarbonate (HCO3
-
) production which in turn helps neutralize the acidified gastric
content
• Promotes secretion of pancreatic digestive enzymes trypsin, chymotrypsin and
carboxypeptidase in their in active forms
• Protein digestive enzymes in Intestine:
– Enzymes (Trypsin, chymotrypsin carboxypeptidase , and aminopeptidase) are produced in
inactive forms called zymogens and are activated at their site of action.
– Trypsin, chymotrypsin and carboxypeptidase in pancreatic juice released into the small
intestine help hydrolyze proteins to smaller peptides
– Aminopeptidase secreted by intestinal mucosal membrane further hydrolyze the small
peptides to amino acids
• Amino acids liberated are transported into blood stream via active transport process

Protein Digestion and Absorption
Section 26.1

Section 26.2
Amino acid pool
• Amino acids formed through digestion process enters
the amino acid pool in the body:
– Amino acid pool: the total supply of free amino acids
available for use in the human body.
• The amino acid pool is derived from 3 sources:
– Dietary protein
– Protein turnover: A repetitive process in which the
body proteins are degraded and resynthesized
– Biosynthesis of amino acids in the liver
– only non-essential amino acids are synthesized

Section 26.2
Amino Acids
Amino acids from the body's amino acid pool are used in four different ways:
1. Protein synthesis:
• About 75% of amino acids go into synthesis of proteins that is needed
continuous replacement of old tissues (protein turnover) and to build
new tissues (growth).
2. Synthesis of non-protein nitrogen-containing compounds:
• Synthesis of purines and pyrimidines for nucleic acid synthesis
• Synthesis of heme for hemoglobin, neurotransmitters and hormones
3. Synthesis of nonessential amino acids:
• Essential amino acids can’t be synthesized because of the lack of
appropriate carbon chain
4. Production of energy
• Amino acids are not stored in the body, so the excess is degraded
• Each amino acid has a different degradation pathway

Section 26.2
Degradation Pathways
• Degradation of an amino acid
takes place in two stages:
̶ The removal of the -amino
group and
̶ The degradation of the
remaining carbon skeleton
• The amino nitrogen atom is
removed and converted to
ammonium ion, which ultimately
is excreted from the body as
urea.
• The remaining carbon skeleton
is then converted to pyruvate,
acetyl CoA, or a citric acid cycle
intermediate, depending on its
makeup, with the resulting
energy production or energy
storage.

Section 26.3
Transamination and Oxidative Deamination
• Removal of amino group is a two step
process: transamination and oxidative
deamination
• Transamination - an enzyme
-catalyzed biochemical process in
which the amino group of an alpha-
amino acid is transferred to an alpha-
keto acid.
- There are at least 50
transaminase enzymes
associated with transamination
reactions
• Oxidative deamination- an amino
acid is converted into the
corresponding keto acid by the
removal of the amine functional group
as ammonia and the ammonia
eventually goes into the urea cycle.

Section 26.3
• By
transamination,
the body can
manufacture
the amino acids
that it needs
but does not
have
• an essential
part of the
active site of
transaminases
is pyridoxal
phosphate
(PLP), the
coenzyme form
of Vit B6

Section 26.3
Oxidative Deamination
• Oxidative deamination is a
catabolic reaction whereby
the α-amino group of an
amino acid is removed,
forming an α-keto acid and
ammonia
• occurs primarily in the liver
and the kidneys through the
activity of the enzyme amino
acid oxidase
• Two amino acids, serine and
threonine, undergo direct
deamination by dehydration-
hydration process rather
than oxidative deamination
a-Glutamate + H2O a-Ketoglutarate + NH4
+
NADH + H+
NAD+
Glutamate
Dehydrogenase

Section 26.4
The Urea Cycle
• The ammonium ion produced by oxidative deamination is a toxic substance,
so it is quickly converted to carbomyl phosphate and then to urea via the
urea cycle in mammals
• in the conversion of ammonia to urea, three different amino acids are
involved: arginine, citrulline, and ornithine; the pathway is called urea cycle
or Krebs Ornithine Cycle
• the blood picks up the urea from the liver and carries it to the kidneys where
it is excreted in the urine.
• urea is the principal end product of protein metabolism and contains a large
percentage of the total nitrogen excreted by the body
• the urea cycle is the only means the body has of removing ammonia; failure
of any part of this cycle leads to an accumulation of ammonia with severe
retardation or death

Section 26.4
The Urea Cycle
• Stage 1: Carbomyl group transfer
– The carbamoyl group of carbamoyl
phosphate is transferred to
ornithine to form citrulline
• Stage 2: Citrulline-aspartate
condensation
– Citrulline is transported into the
cytosol, citrulline reacts with
aspartate to produce
argininosuccinate utilizing ATP
• Stage 3: Argininosuccinate cleavage:
– Argininosuccinate is cleaved to
arginine and fumarate by the
enzyme argininosuccinate lyase
• Stage 4: Hydrolysis of urea from
arginine:
– Hydrolysis of arginine produces
urea and regenerates ornithine -
one of the cycle’s starting materials

Section 26.4
The Urea Cycle
Linkage Between the Urea and Citric Acid Cycles
• Fumarate from the urea cycle enters the citric acid
cycle, and aspartate produced from oxaloacetate of
the citric acid cycle enters the urea cycle.

Section 26.5
Amino Acid Carbon Skeletons
• Each of 20 amino acid carbon skeletons undergo a different
degradation process
• 7 Degradation products are pyruvate, acetyl CoA, acetoacetyl CoA,
alpha-ketoglutarate, succinyl CoA, fumarate, and oxaloacetate
– Last four are intermediates in the citric acid cycle
• The amino acids converted to citric acid cycle intermediates can
serve as glucose precursors (glucogenic amino acids).
– Glucogenic amino acid: An amino acid that has a carbon-
containing degradation product that can be used to produce
glucose via gluconeogenesis.
• The amino acids converted to acetyl CoA or acetoacetyl CoA can
serve as precursors for fatty acids and/or ketone body synthesis
(ketogenic amino acids)
– Ketogenic amino acid: An amino acid that has a carbon-
containing degradation product that can be used to produce
ketone bodies

Section 26.5
• even though acetyl CoA can enter
the TCA cycle, there can be no net
production of glucose from it; acetyl
groups are C2 species and such
species only maintain the carbon
count in the cycle, because 2 CO2
molecules exit the cycle. Thus, amino
acids that are degraded to acetyl
CoA (or acetoacetyl CoA) are NOT
glucogenic.
• amino acids that are degraded to
pyruvate can be either glucogenic
or ketogenic; pyruvate can be
metabolized to either oxaloacetate
(glucogenic) or acetyl CoA
(ketogenic)
• only two (2) amino acids are purely
ketogenic: Leu & Lys; nine (9) amino
acids are both glucogenic and
ketogenic (those degraded to
pyruvate) as well as Tyr, Phe, & Ile
(which have two degradation
products); the remining nine (9)
amino acids are purely glucogenic

Section 26.5
• Non essential amino acids are
synthesized in 1-3 steps
• Essential amino acids are
synthesized in 7-10 steps
• three of the nonessential amino
acids (ala, asp, and glu) are
biosynthesized by transamination
of the appropriate α-keto acid
starting material
• the nonessential amino acid tyr is
obtained from the essential
amino acid phe in a one-step
oxidation that involves molecular
O2, NADPH, and the enzyme
phenylalanine hydroxylase;
• lack of this enzyme causes the
metabolic disease
phenylketonuria (PKU)
Summary of the Starting Materials for the Biosynthesis of the 11
Nonessential Amino Acids

Section 26.5

Section 26.7
Hemoglobin Catabolism
• Red blood cells (RBCs) are highly specialized cells whose primary
function is to deliver oxygen to cells and remove carbon dioxide
from body tissues
• Hemoglobin is a conjugated protein with two parts:
– Protein portion is globin
– Prosthetic group is heme
• Iron atom interacts with oxygen forming a reversible complex
(oxygen can come on and out) with it
• Mature red blood cells have no nucleus or DNA -- filled with red
pigment hemoglobin
• Red blood cells are formed in the bone marrow
– ~ 200 billion new red blood cells are formed daily
• The life span of a red blood cell is about 4 months

Section 26.7
• Old RBCs are broken down in the spleen (primary site)
and liver (secondary site):
• Degradation of hemoglobin
– Globin protein part is converted to amino acids and
are put in amino acid pool
– Fe atom becomes part of ferritin -- an iron storage
protein -- saves the iron for use in biosynthesis of
new hemoglobin molecules
– The heme (tetrapyrrole) is degraded to bile pigments
and eliminated in feces or urine.

Section 26.7
Bile Pigments
• Bile pigments: The tetrapyrrole degradation products secreted via the bile.
• There are four bile pigments:
– Biliverdin - green in color
– Bilirubin - reddish orange in color.
– Stercobilin – brownish in color (gives feces their characteristic brown
color).
– Urobilin - yellow in color and present in urine (gives characteristic
yellow color to urine).
• Daily normal excretion of bile pigments: 1–2 mg in urine and 250–350 mg in
feces.
• Jaundice: Results from liver, spleen and gallbladder malfunction.
– Results in higher than normal bilirubin levels in the blood and gives the
skin and white of the eye yellow tint.

Section 26.8
Interrelationships Among Metabolic Pathways
• The metabolic pathways of
carbohydrates, lipids, and proteins
are integrally linked to one another.
− A change in one pathway can
affect many other pathways.
• Examples:
− Feasting (over eating):
Causes the body to store a
limited amount as glycogen
and the rest as fat.
− Fasting (no food ingestion):
The body uses its stored
glycogen and fat for energy.
− Starvation (not eating for a
prolonged period):
− Glycogen stores are
depleted,
− Body protein is broken
down to amino acids to
synthesize glucose.
− Fats are converted to
ketone bodies.

Section 26.8

Section 26.9
B-Vitamins and Protein Metabolism
• Structurally modified B-
vitamins function as
coenzymes in protein
metabolism as well
• All 8 B-Vitamins participate
in various pathways of
protein metabolism:
– Niacin – NAD+ and
NADH – oxidative
deamination reactions
– PLP – transamination
reactions
– All 8 B-vitamins –
Degradation and
biosynthesis of amino
acids

Chem 45 Biochemistry: Stoker chapter 26 Protein Metabolism

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