Chem 45 Biochemistry: Stoker chapter 26 Protein Metabolism

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+

GlutamateDehydrogenase

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 26.8



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


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Chem 45 Biochemistry: Stoker chapter 26 Protein Metabolism

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