Download MBBS Biochemistry PPT 33 Amino Acid Oxidation Lecture Notes

Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 33 Amino Acid Oxidation Notes. - biochemistry notes pdf, biochemistry mbbs 1st year notes pdf, biochemistry mbbs notes pdf, biochemistry lecture notes, paramedical biochemistry notes, medical biochemistry pdf, biochemistry lecture notes 2022 ppt, biochemistry pdf.


Amino-acid Oxidation

Department of Biochemistry

Specific Learning Objectives

Fates of Amino Acids
Amino Acid Utilization
Amino-group metabolism
Explain role of transamination reactions in aa synthesis and identify vitamin

essential for this reaction (tie in to urea cycle)

Describe interconversion between ketoacids and aa, including requirement of

pyridoxal phosphate (PLP) as a cofactor

Outline formation and transport of ammonia
Describe importance of reactions catalyzed by glutamine synthetase, glutaminase,

and glutamate dehydrogenase

Ammonia Intoxication
List causes for hyperammonemia, its consequences, and treatments to reduce

blood ammonia levels
Overview of AA catabolism

Fig18.1: Lehninger Principles of Biochemistry by David L Nelson, 6th Ed

Amino Acid oxidative degradation

It occurs in three metabolic circumstances:
1. During normal synthesis and degradation of Proteins (Protein turnover)
? Some aa released from proteins breakdown and not needed for new protein

synthesis

2. If diet is rich in protein and ingested aa exceeds the body needs for protein

synthesis, in this case surplus catabolized

2. During starvation or in uncontrolled diabetes, when carbohydrates either

unavailable or not properly utilized, in this case cellular proteins are used as a

fuel
Cont--

Under all above conditions, aa lose their amino groups to form -keto acids and

also form carbon skeletons of aa:

? -keto acids undergo oxidation to CO and H O

2

2

? 3-4 carbon units its converted into glucose by gluconeogenesis, fuel for brain,

skeletal muscel and other tissues

Four aa plays imp role in nitrogen metabolism: Glutamate, Glutamine, (both

converted to -ketoglutarate), Alanine (to pyruvate) and Aspartate (to

oxaloacetate)

Fates of Amino Acids

For Protein synthesis
For synthesis of other nitrogen containing compounds (heme, creatine,

purines, pyrimidines, choline, neurotransmitters)

For gluconeogenesis
Energy source from glucogenic aa and ketogenic aa

Glucogenic aa: Give rise to a net production of pyruvate or TCA cycle

intermediates, such as -ketoglutarate , succinyl CoA, Fumarate and

oxaloacetate, all of which are precursors to glucose via gluconeogenesis.

Ex. Ala & Arg
Cont--

Ketogenic aa: Lysine and leucine are only aa are ketogenic, give rise to

acetyl-CoA or acetoacetyl-CoA, neither of which can bring about net

glucose production

Glucogenic and Ketogenic aa: Small group of aa comprised of Ile, Phe,

Thr, Trp, and Tyr give rise to both glucose and fatty acid precursors and

characterized as glucogenic and ketogenic

Steps for Amino group catabolism

In cytosol of liver cells, amino groups from most aa transferred to -

ketoglutarate to form glutamate, which enters mitochondria and gives up its

amino group to form ammonia

Excess ammonia generated in most tissues converted to amide nitrogen of

glutamine, which passes to liver, then into liver mitochondria

In skeletal muscle, excess amino groups are transferred to pyruvate to form

alanine

Aspartate come into play in metabolic processes that occur once amino

groups delivered to liver
Amino group catabolism

Fig18.2 (a): Lehninger Principles of Biochemistry by David L Nelson, 6th Ed

Amino Acid Utilization

Degradation of an aa in two stages:

a) Carbon skeleton, is then converted to

pyruvate, acetyl CoA, or citric acid cycle

intermediate, depending on its makeup,

with resulting energy production or

energy storage

b) Amino nitrogen atom is removed and

converted to ammonium ion, which

ultimately excreted from body as urea.
Amino-group metabolism

? -amino group is nitrogen source during aa

metabolism

? Nitrogen is removed from aa as a ammonia, which

needs to be detoxified to urea

Three steps involved in flow of nitrogen from aa to

urea:
(1) Transamination (amino group transferred to

glutamate),

(2) Oxidative deamination of glutamate (removal of

amino group),

(3) Synthesis of Urea

Fig 19.15. Lippincott's Illustrated Reviews, Biochemistry, 6th Ed

Transamination

? -NH2 group of one aa is transferred

to a -ketoacid resulting in formation

of a new aa and a new ketoacid

? Donor aa (I) becomes a new ketoacid

(I) after losing the -NH2 group, and

recipient ketoacid (II) becomes a new

aa (II) after receiving the NH2 group

Text Book of Medical Biochemistry by Chatterjee & Rana Shinde, 8th Ed
Cont--

? -amino group from L-amino acid is

transferred to -carbon atom of -

ketoglutarate, produced -keto acid and

glutamate

? Transfer of amino groups from one carbon

skeleton to another is catalyzed by

aminotransferases

? Al aminotransferases have prosthetic group,

which is pyridoxal phosphate (PLP),

coenzyme form of pyridoxine or vitamin B

Fig18.4: Lehninger Principles of Biochemistry by David L Nelson

6

Cont--

? PLP participates in transfer of -amino groups to -

ketoglutarate

? Location: cytoplasm of all cells

? Enzyme: Transaminases (aminotransferases)

? Co-factor: Pyridoxal phosphate (PLP), derivative of

vitamin B6

? Common donor/acceptor pair: -ketoglutarate and

glutamate
Cont--

Glutamate function as excretion pathways that lead to elimination of

nitrogenous waste products

Al aa except lysine and threonine participate in transamination in

their catabolism but they undergo deamination reaction

Two aminotransferase reactions are catalyzed by alanine

aminotransferase (ALT ) and aspartate transferases (AST)

Cont--

Alanine aminotransferase: In this alanine is donor aa and

-ketoglutarate is recipient ketoacid resulting in formation

of pyruvate and glutamate.
? During aa catabolism, this enzyme functions in direction

of glutamate synthesis.

Aspartate aminotransferase: In this Aspartic acid is donor

aa and -ketoglutarate is recipient ketoacid.
? During aa catabolism, this enzyme transfers amino

groups from glutamate to oxaloacetate, forming

aspartate, which is used as a source of nitrogen in urea

cycle.

Fig 19.8. Lippincott's Illustrated Reviews, Biochemistry, 6th Ed
Diagnostic value of plasma aminotransferases

Alanine aminotransferase
Normal enzyme activity is 3 to 15 IU/L
It is entirely cytoplasmic
Increases in viral hepatitis, diabetes, congestive heart failure, liver

damage

Aspartate aminotransferase
Normal enzyme activity is 4 to 17 I.U/L
It is cytoplasmic and also mitochondrial
Increases in Liver diseases, muscular dystrophies, acute pancreatitis,

leukaemias, acute haemolytic anaemia

Oxidative Deamination

? Glutamate releases its amino group as ammonia in

Liver

? Amino groups from many of -aa are collected in liver

in form of amino group of L-glutamate molecules

L-Glutamate semialdehyde

? These amino groups must next be removed from

glutamate to prepare them for excretion

? In hepatocytes, glutamate is transported from cytosol

into mitochondria, where it undergoes oxidative

deamination

catalyzed

by

L-glutamate

Fig18.7: Lehninger Principles of Biochemistry by David L Nelson, 6th Ed

dehydrogenase
Cont--

It is only enzyme that can use either NAD+ or NADP+ as acceptor of

reducing equivalents

Oxidative deamination of glutamate is main mechanism for release of

aa nitrogen as ammonia (NH4+) in a reversible reaction.

Location: Mitochondria of hepatocytes

Al osteric regulation of oxidative deamination: High energy state inhibits

GDH and low energy state stimulates enzyme.

Transdeamination

Transfer of amino nitrogen to -ketoglutarate forms l-glutamate by

glutamate aminotransferases

Hepatic l-glutamate dehydrogenase (GDH), which can use either NAD+ or

NADP+, convert glutamate to -ketoglutarate, releases this nitrogen as

ammonia, this -ketoglutarate used in TCA cycle and glucose synthesis

Conversion of -amino nitrogen to ammonia by coordinated action of

glutamate aminotransferase and GDH is "transdeamination"
Cont--

Liver GDH activity is allosterically inhibited by ATP, GTP, and NADH,

and is activated by ADP

GDH reaction is freely reversible, and also functions in aa

biosynthesis

-ketoglutarate formed from glutamate deamination can be used in

citric acid cycle and for glucose synthesis

Clinical-cases discussed
Thank you

This post was last modified on 05 April 2022