Download MBBS Biochemistry PPT 35 Biochemistry II Lecture Notes

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Department of Biochemistry

Learning Objectives

? Fates of Amino Acids

? Sources of Amino Acids

? Amino Acid Utilization

? Nitrogen Balance

? Amino-group metabolism

? Transamination

? Deamination

? Transdeamination

? Transamidation
? Decarboxylation

? Transmethylation
Role of Glutathione in Amino Acid Absorption

? Meister proposed that glutathione participates in an active

group translocation of L-amino acids (except L-Pro) into cells of

small intestine, kidneys, seminal vesicles, and brain.

? He proposed a "cyclic" pathway/-glutamyl cycle in which

Glutathione is regenerated again

? -glutamyl transferases (GGT) plays a key role in this cycle, a

pathway for synthesis and degradation of glutathione and drug

and xenobiotic detoxification

-glutamyl/Meister cycle

Fig.26.1: Text Book of Medical Biochemistry by Chatterjee & Rana Shinde, 8th Ed
Disorder related to aa transporter

Hartnup disease: Defect in SCL6A19 gene, it is a sodium-

dependent and chloride independent neutral aa transporter,

expressed in kidneys and intestine

? This gene controls the absorption of certain aa from intestine

and reabsorption of those aa in kidneys

? Person with Hartnup disease cannot absorb aa properly from

intestine and cannot reabsorb them from tubules in kidneys

Cont--

? Resulting excessive amount of aa such as Trp excreted in urine

? Due to inadequate amount of Trp, body not able to make sufficient

amount of niacin (vit B3), which is necessary component of NAD+

? Pellagra, a similar condition, is also caused by low nicotinamide; this

disorder results in dermatitis, diarrhea, and dementia
Cont--

? Cystinuria: Dibasic (diamino aa) transporter Lys, Arg, Ornithine

and Cys. If there is any defect in this transport system, it leads

to Cystinuria

? In medicine, Garrod's tetrad is a term named for British

physician Archibald Garrod, who introduced the phrase "inborn

errors of metabolism" in a lecture in 1908

? Tetrad comprises four inherited metabolic diseases: albinism,

alkaptonuria, Cystinuria and pentosuria

Fates of Amino Acids

? For Protein synthesis

? For synthesis of other nitrogen containing compounds (heme,

creatine, purines, pyrimidines, choline, neurotransmitters)

? For the 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 the only aa are ketogenic,

giving rise only to acetylCoA or acetoacetylCoA, neither of which

can bring about net glucose production. Ex. Leu and Lys

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

Sources of Amino Acids

? Ingested dietary proteins is hydrolysed to aa and absorbed from

the intestine

? Breakdown of tissue/body proteins

? Glycolysis and citric acid cycle

? Synthesis of non-essential aa
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 the resulting energy production or

energy storage

b) Amino nitrogen atom is removed and

converted to ammonium ion, which

ultimately is excreted from the body as

urea.

Nitrogen Balance

Nitrogen balance occurs when synthesis of body protein equals

degradation.

? Amount of nitrogen excreted in the urine each day equals the

amount of nitrogen ingested each day

Positive nitrogen balance occurs when synthesis of body protein

excess compare to degradation.

? Less nitrogen is excreted than ingested (growth, e.g. growing

infants and children, pregnant women, tissue repair)
Cont--
Negative nitrogen balance occurs when synthesis of body protein

lesser compare to degradation.

? More nitrogen is excreted than ingested (malnutrition, absence

of one or more essential aa in diet)

? It occurs in injury, stress response, malnutrition of essential aa

Amino-group metabolism

? -amino group is the 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--
? Transfer of an -amino group from one aa to an

-keto acid in a reversible reaction

? 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 then functions as excretion pathways that lead to the

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 the donor aa and -

ketoglutarate is the recipient ketoacid resulting

in formation of pyruvate and glutamate.

? During amino acid catabolism, this enzyme

functions in the direction of glutamate synthesis.

Aspartate aminotransferase
? In this Aspartic acid is the donor amino acid and

-ketoglutarate is the recipient ketoacid.

? During aa catabolism, this enzyme transfers

amino groups from glutamate to oxaloacetate,

forming aspartate, which is used as a source of

Fig 19.8. Lippincott's Illustrated Reviews, Biochemistry, 6th Ed

nitrogen in the urea cycle.

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
Deamination

? In oxidative deamination reactions result in the

liberation of the amino group as free ammonia

? Amino groups from many of the -aa are collected

in the liver in the form of the amino group of L-

glutamate molecules

? These amino groups must next be removed from

L-Glutamate semialdehyde

glutamate to prepare them for excretion

? In hepatocytes, glutamate is transported from the

cytosol into mitochondria, where it undergoes

oxidative deamination catalyzed by L-glutamate

Fig18.7: Lehninger Principles of Biochemistry by David L Nelson

dehydrogenase

Cont--

? It is the only enzyme that can use either NAD+ or NADP+ as the

acceptor of reducing equivalents

? This oxidative deamination of glutamate is the main mechanism for

release of aa nitrogen as ammonia (NH +) in a reversible reaction.

4

? Location: Mitochondria of hepatocytes

? Allosteric regulation of oxidative deamination: High energy state

inhibits the GDH and low energy state stimulates the enzyme.
Transdeamination

? Transfer of amino nitrogen to -ketoglutarate forms l-

glutamate.

? Hepatic l-glutamate dehydrogenase (GDH), which can use

either NAD+ or NADP+, releases this nitrogen as ammonia

? Conversion of -amino nitrogen to ammonia by the 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

? The -ketoglutarate formed from glutamate deamination can be

used in the citric acid cycle and for glucose synthesis
Transamidation

? Transamidation involves transfer of ?NH2 from a

carboxamide group to a suitable acceptor

? Formation of glucosamine-6-P:The amide-N of glutamine

can be transferred to a ketogroup

? If transferred to a Keto group of fructose-6-P, it forms

Glucosamine-6-P by a transamidation reaction from

Glutamine as the 1st step of hexosamine biosynthesis

pathway

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

Decarboxylation

? Reaction by which CO2 is removed

from the COOH group of an aa as a

result an amine is formed

? This reaction is catalysed by

decarboxylase,

which

requires

pyridoxal-P (B6-PO4) as coenzyme

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

? The enzyme removes CO2 from COOH

gr.

and

converts

the

aa

to

corresponding amine
Cont--

? End-product of this pathway is UDP-GlcNAc, used to make

glycosaminoglycans, proteoglycans and glycolipids

? The catalysing enzyme is L-glutamine-D-fructose-6-P

transamidase

Cont--

? This is mostly a process confined to putrefaction in intestines

and produces amines

? Ex. Threonine is converted into Propanol amine (Constituent of

Vit B12)

? Isoleucine undergoes transamination, followed by oxidative

decarboxylation of resulting -keto acid
Transmethylation

? Transmethylation Certain compounds of

the body, with structures containing

CH3 group attached to an atom other

than carbon can take part in enzymatic

reactions

? Whereby these ?CH3 groups are

transferred to a suitable "acceptor",

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

which have no ?CH3 group

Cont--

? Such reactions are termed as "transmethylation reaction", and

the substrate, i.e. the ?CH3 donor is said to possess biologically

labile ?CH3 group"

? Most important compounds with biologically labile methyl group

are active methionine
Transmethylation reactions

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

Group Discussion

? Subtopics of previous class discussed in groups.
Reference Books

1) Text Book of Medical Biochemistry by Chatterjee & Rana

Shinde, 8th Ed

2) Biochemistry, Lippincott's Il ustrated Reviews, 6th Ed
3) Harper's Il ustrated Biochemistry-30th Ed
4) Lehninger Principles of Biochemistry

33

Thank you

This post was last modified on 05 April 2022