MSLSC2001C04 Course Instructor Dr. Gautam Kumar · Dr. Gautam Kumar Dr.Gautam Kr. Dept. of Life Sc....

Metabolism MSLSC2001C04

Course Instructor Dr. Gautam Kumar

Dr.Gautam Kr. Dept. of Life Sc. 1

Cell Receptors

Antibodies Dr.Gautam Kr. Dept. of Life Sc.

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Biosynthesis of Amino Acids


*

*

• Biosynthetic pathways is to group them into six families corresponding to their metabolic precursors

• 5-phosphoribosyl-1- pyrophosphate (PRPP)

• Intermediate in several pathways of amino acid and nucleotide synthesis it is synthesized from ribose 5-phosphate derived from the pentose phosphate pathway

* A.A. that are essential for infants


Overview of amino acid biosynthesis


• Plants and Bacteria synthesize all 20 common amino acids.

• Mammals can synthesize about half; the others are required in the diet (Essential amino acids).

• Reductive amination of α-keto acids

• Formation of the amides of aspartic and glutamic acids

Ammonium ions incorporated into a.a. By two principles


• α-Ketoglutarate Gives Rise to Glutamate, Glutamine, Proline, and Arginine

• Serine, Glycine, and Cysteine Are Derived from 3-Phosphoglycerate

• Three Nonessential and Six Essential Amino Acids Are Synthesized from Oxaloacetate and Pyruvate

• Chorismate, an intermediate in the synthesis of aromatic amino acids in bacteria and plants.

• Plants and bacteria produce the reduced sulfur required for the synthesis of cysteine (and methionine, from environmental sulfates


• Chorismate Is a Key Intermediate in the Synthesis of Tryptophan, Phenylalanine, and Tyrosine

• Phosphoribosyl pyrophosphate is a precursor of tryptophan and histidine.


Amino acid derivatives • Glycine Is a Precursor of Porphyrins

Porphyrin nucleus in Heme proteins such as hemoglobin and the cytochromes

• In mammals and other higher eukaryotes, δ-aminolevulinate is synthesized from glycine and succinyl-CoA.

• In bacteria and plants, the precursor of δ–aminolevulinate is glutamate.


• Creatine and Phospocreatine is synthesized from glycine and arginine

• Glutathione (GSH), present in plants, animals, and some bacteria, often at high levels. It is derived from glycine, glutamate, and cysteine

• Phosphocreatine, derived from creatine, is an important energy buffer in skeletal muscle

To remove toxic peroxides formed in the normal course of growth and metabolism under aerobic conditions

• D-Amino Acids Are Found Primarily in Bacteria cell wall and peptide antibiotics

Bacterial peptidoglycans contain both D-alanine and D-glutamate

L-fluoroalanine and Cycloserine are D- amino acid use in tuberculosis

Dr. Gautam Kr. Dept. of Life Sc. 11

Aromatic Amino Acids Are Precursors of Many Plant Substances

The rigid polymer lignin, derived from phenylalanine and tyrosine

Tryptophan is also the precursor of the plant growth hormone indole-3-acetate, or auxin

Phenylalanine and tyrosine also give rise to many commercially significant natural products, including the tannins, morphine, flavoring of cinnamon oil (Cinnamate), nutmeg, cloves, vanilla, cayenne pepper, and other products

• Many important neurotransmitters are primary or secondary amines, derived from amino acids

• Polyamines such as spermine and spermidine, involved in DNA packaging, are derived from methionine and ornithine

• Arginine Is the Precursor for Biological Synthesis of Nitric Oxide


• PLP-dependent decarboxylation


AMINO ACID OXIDATION

• Carnivores can obtain up to 90% of their energy requirements from amino acid oxidation, whereas herbivores may fill only a small fraction of their energy needs by this route


• Amino acid concentrations in plant tissues are carefully regulated to just meet the requirements for biosynthesis of proteins, nucleic acids, and other molecules needed to support growth.

Carnivores plants


Dietary Protein Is Enzymatically Degraded to Amino Acids

Trypsinogen, Chymotrypsinogen, and Procarboxypeptidases A and B, the zymogens of trypsin, chymotrypsin, carboxypeptidases A and B, are synthesized and secreted by the exocrine cells of the pancreas

Blood vessels


• All these metabolic conditions, amino acids lose their amino groups to form α-keto acids, the “carbon skeletons” of amino acids.

• The α-keto acids undergo oxidation to CO2 and H2O or, often more importantly, provide three and four-carbon units that can be converted by gluconeogenesis into glucose, the fuel for brain, skeletal muscle, and other tissues.

• Most amino acids are metabolized in the liver

• Ammonia generated in this process is recycled and used in a variety of biosynthetic pathways; the excess is either excreted directly or converted to urea or uric acid for excretion, depending on the organism


• The first step in the catabolism of most L-amino acids, once they have reached the liver

• Removal of the α- amino groups, promoted by enzymes called aminotransferases or transaminases.

Transamination

Glutamate then functions as an amino group donor for biosynthetic pathways

There is no net deamination (loss of amino groups) in these reactions because the α-ketoglutarate becomes aminated as the α-amino acid is deaminated.

To collect the amino groups from many different amino acids in the form of L-glutamate.

All aminotransferases have pyridoxal phosphate (PLP) as cofactor.

• Glutamate Releases Its Amino Group as Ammonia in the Liver

liver


Ammonia transport in the form of glutamine

• Excess ammonia in tissues is added to glutamate to form glutamine, a process catalyzed by glutamine synthetase.

• After transport in the bloodstream, the glutamine enters the liver and NH+

4 is liberated in mitochondria by the enzyme glutaminase.

• Glutamate Releases Its Amino Group as Ammonia in the Liver

urea cycle


• In ureotelic organisms, the ammonia deposited in the mitochondria of hepatocytes is converted to urea in the urea cycle.

• Carbamoyl phosphate required in urea synthesis is made in mitochondria matrix by Carbamoyl phosphate synthetase -I


Urea cycle and reactions that feed amino groups into the cycle

• Ammonia is highly toxic to animal tissues. In the urea cycle, ornithine combines with ammonia, in the form of carbamoyl phosphate, to form citrulline. Dr.Gautam Kr. Dept. of Life Sc.

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Links between the urea cycle and citric acid cycle

• The urea cycle results in a net conversion of oxaloacetate to fumarate, both of which are intermediates in the citric acid cycle. The two cycles are thus interconnected.


Alanine Transports Ammonia from Skeletal Muscles to the Liver

• Alanine also plays a special role in transporting amino groups to the liver in a nontoxic form, via a pathway called the glucose-alanine cycle

• In muscle and certain other tissues that degrade amino acids for fuel, amino groups are collected in the form of glutamate by transamination

• Glutamate can be converted to glutamine for transport to the liver, as described above, or it can transfer its -amino group to pyruvate, a readily available product of muscle glycolysis, by the action of alanine aminotransferase


The carbon skeletons are diverted to gluconeogenesis or ketogenesis or are completely oxidized to CO2 and H2O.

• All or part of the carbon skeletons of seven amino acids are ultimately broken down to acetyl-CoA

• Some Amino Acids Are Converted to Glucose, Others to Ketone Bodies

• Alanine, glycine, serine, cysteine, tryptophan, and threonine: Pyruvate

• Tryptophan, lysine, phenylalanine, tyrosine, leucine, and isoleucine: Acetyl-CoA

• Arginine, histidine, glutamate, glutamine, and proline: α-Ketoglutarate

• Methionine, isoleucine, threonine, and valine: Succinyle CoA

• Asparagine and Aspartate Are Degraded to Oxaloacetate Dr.Gautam Kr. Dept. of Life Sc.

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Genetic Disorders Affecting Amino Acid Catabolism


• Branched-Chain Amino Acids Are Not Degraded in the Liver: Valine, isoleucine, and leucine

• Branched side chains (leucine, isoleucine, and valine) are oxidized as fuels primarily in muscle, adipose, kidney, and brain tissue. These extrahepatic tissues contain an aminotransferase, absent in liver


Summary of amino acid catabolism


MSLSC2001C04 Course Instructor Dr. Gautam Kumar · Dr. Gautam Kumar Dr.Gautam Kr. Dept. of Life Sc....

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