Download MBBS (Bachelor of Medicine, Bachelor of Surgery) 1st year (First Year) Biochemistry ppt lectures Topic 40 Catabolism Of Carbon Skeletons Of Amino Iii 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.
Catabolism of Carbon Skeletons of amino
acids and related disorders-III
Specific Learning Objectives
Integrate aa synthesis with specific precursors from glycolysis, citric acid
cycle and pentose phosphate pathway
List which aa are precursors to citric acid cycle intermediates and identify
specific intermediates (in addition to Acetyl-CoA and Acetoacetyl-CoA)
Catabolic pathways of seven aa to Acetyl-CoA
Summary of Amino acid Catabolism
Fig18.15: Lehninger Principles of Biochemistry by David L Nelson
Introduction
Carbon skeletons are generally conserved as:
Carbohydrate, via gluconeogenesis
Fatty acid via fatty acid synthesis pathways
These pathways converge to form seven intermediate products:
Oxaloacetate, -ketoglutarate, pyruvate, fumarate, succinyl coenzyme A
(CoA) , acetyl CoA, and acetoacetate
Cont--
These products directly enter pathways of intermediary metabolism:
Resulting either in synthesis of glucose or lipid or in production of
energy through their oxidation to CO2 and water by citric acid cycle
Catabolic pathways of six aa to Pyruvate
Fig18.19: Lehninger Principles of Biochemistry by David L Nelson
Cont--
Glycine cleavage system is multienzyme complex: It consists of four proteins:
1. PLP-dependent glycine decarboxylase (P-protein)
2. Lipoamide-containing aminomethyl carrier (H-protein), which carries
aminomethyl group remaining after glycine decarboxylation
3. N5,N10-methylene-THF synthesizing enzyme aminomethyltransferase (AMT)
(T-protein), which accepts a methylene group from aminomethyl carrier, amino
group is released as ammonia
4. NAD+-dependent, FAD-requiring dihydrolipoyl dehydrogenase (L-protein), a
protein shared by and known as E3 in pyruvate dehydrogenase complex
https://www.slideshare.net/ashokktt/metabolism-of-glycine
Disorder related to glycine
Non-ketotic hyperglycinemia (NKH)
Humans with serious defects in glycine cleavage system activity due
to absence of one of components of glycine cleavage system
Elevated serum levels of glycine, leading to mental retardation and
death in very early childhood
Cont--
In one of glycine degradation pathway, glycine is converted into
glyoxylate by D-amino acid oxidase
Glycine is precursor of glyoxalate, which can be transaminated back to
glycine or oxidized to oxalate by lactate dehydrogenase
Excessive production of oxalate forms the insoluble calcium oxalate
salt, lead to kidney stones.
Two pathways catabolize cysteine
Fig 29.9: Harper's Illustrated Biochemistry 30th Edition
Disorders related to Cysteine
Cystinuria is caused by mutations in SLC3A1 and SLC7A9 genes.
These defects prevent reabsorption of basic positively charged aa
(Cysteine, lysine, ornithine and arginine)
Under normal condition, these proteins allow certain aa including cysteine
to be reabsorbed into blood from filtered fluid that wil become urine
Mutations in either of these genes disrupt ability of this transporter protein
exist in kidney tubules to reabsorb these aa, allowing them to excretion of
these aa in urine
Cystinosis
Cystinosis is a lysosomal storage disease in which abnormal
accumulation of cystine, leads to intracellular crystal formation throughout
body. Cystine: It is formed from oxidation of two cysteine molecules, via formation of a
disulfide bond)
Cystinosis is most common cause of Fanconi syndrome in pediatric age
group
Fanconi syndrome occurs when function of cells in renal tubules is
impaired, leading to abnormal amounts of carbohydrates and amino acids
in urine, excessive urination, and low blood levels of potassium and
phosphates
Catabolic pathway of Hydroxyproline
Harper's Illustrated Biochemistry 30th Edition
Disorders related to Hydroxyporoline
Type II hyperprolinemia: A defect in 4-hydroxyproline dehydrogenase results
in hyperhydroxyprolinemia, an excess of free hydroxyproline in plasma and
urine
Associated with mental retardation
Type II hyperprolinemia: A defect in glutamate--semialdehyde
dehydrogenase/ 1-pyrroline-3-hydroxyl-5-carboxylate dehydrogenase
Type II hyperprolinemia is a rare form of disorder may appear benign at
time but often involves seizures, convulsions and intellectual disability
Catabolic pathways of seven aa to Acetyl-CoA
Fig18.21: Lehninger Principles of Biochemistry by David L Nelson
Cont--
Tryptophan breakdown is most complex of all pathways of aa
catabolism in animal tissues
Portions of tryptophan (four of its carbons) yield acetyl-CoA via
acetoacetyl CoA
Some of intermediates in tryptophan catabolism are precursors for
tsynthesis of other biomolecules, including nicotinate, a precursor of
NAD and NADP, serotonin
Catabolism of Tryptophan to -Ketoadipate
Fig 29.16. Harper's Illustrated Biochemistry 30th Edition
Disorder related to Tryptophan
Hartnup disease: In catabolism of Typ, kynureninase requires PLP (active
form of vit B6), acts on 3-L hydroxylkynurenine
Defect in kynureninase limits tryptophan availability for niacin
biosynthesis, cause reduced synthesis of NAD+ and NADP+ leads to
pellagra-like signs and symptoms.
Due to lack of PLP, Kynureninase reaction blocked and 3-L
hydroxylkynurenine is diverted and form xanthurenate catalyzed by
Kynurenine transferases
Cont--
Elevated levels of xanthurenate shows vit B6 deficiency
Hartnup disease reflects impaired intestinal and renal transport of
tryptophan and other neutral aa
Indole derivatives of unabsorbed tryptophan formed by intestinal
bacteria are excreted
Catabolic pathways of seven aa to Acetyl-CoA
Threonine yield some acetyl CoA also
Fig18.21: Lehninger Principles of Biochemistry by David L Nelson
Saccharopine lysine catabolism pathway
First two steps of saccharopine
pathway are catalysed by bifunctional
enzyme,-aminoadipic semialdehyde
synthase (AASS), which possess
both lysine-ketoglutarate reductase
(LKR)
and
saccharopine
dehydrogenase (SDH) activities
https://en.wikipedia.org/wiki/Lysine
Disorder related to Lysine
Hyperlysinemia: is an autosomal recessive inborn error of L-lysine degradation in liver
and production of acetyl-CoA
? lysine and -ketoglutarate are converted into saccharopine by lysine-ketoglutarate
reductase
? Saccharopine is then oxidized to -aminoadipic semialdehyde and glutamate by
saccharopine dehydrogenase
Both enzyme activities are catalyzed by a single mitochondrial bifunctional enzyme
named -aminoadipic semialdehyde synthase (AASS) which is encoded by gene
AASS
One mutation in AASS, cause hyperlysinemia, along with mental and physical
retardation
Catabolism of Asparagine and Aspartate to Oxaloacetate
Fig18.29: Lehninger Principles of Biochemistry by David L Nelson
Cont--
L-asparaginase is an effective chemotherapeutic agent in treatment of
cancers that must obtain asparagine from blood, particularly acute
lymphoblastic leukemia
26
Reference Books
1) Lehninger Principles of Biochemistry
2) Harper's Il ustrated Biochemistry-30th edition
3) Biochemistry, Lippincott's Il ustrated Reviews, 6th Ed
4) Biochemistry, Donald Voet and Judith G. Voet, 4th Ed.
5) Gregory S. Ducker and Joshua D Rabinowitz. Cel Metab. 2017 Jan 10;25(1):27-
42
Two Clinical-cases discussed
Thank you
This post was last modified on 05 April 2022