Lectures 27/28: Amino Acid Metabolism Flashcards Preview

Biochemistry 2300 > Lectures 27/28: Amino Acid Metabolism > Flashcards

Flashcards in Lectures 27/28: Amino Acid Metabolism Deck (79):
1

Nitrogen

Essential element found in amino acids, nitrogenous bases and many other molecules
Biologically available nitrogen is scarce

2

Nitrogen Fixation

Reduction of N2 by prokaryotic microorganisms to form NH3
Often rate limiting factor in plant growth
High energy requirement
Nitrogen often rate limiting factor in plant growth
Conversion into amide group of glutamine
Catalyzed by nitrogenase complex

3

Free-living cyanobacteria

Most prominent nitrogen-fixing species

4

Symbiotic bacteria

Most prominent nitrogen-fixing species

5

Nitrogen assimilation

Incorporation of inorganic nitrogen compounds into organic molecules
Roots in plants
NH4+ or NO3- incorporated into amino acids

6

NO3

As nitrogen source, two step reaction is used to convert it to NH4+ by nitrite reductase

7

Glutamine synthetase

Catalyzes ATP-dependent reaction of glutamate with NH4+ to form glutamate
Found in all organisms
Entry point in microorganisms for fixed nitrogen
Uses ATP
Glutamate + ammonium to glutamine: formation of irreversible amide bond

8

Phytoplankton bloom

Can trigger dead zone formation
Decomposition carried out by aerobic bacteria: increased oxygen use by bacteria, O2 levels drop, hypoxic conditions for fish

9

Glutamate synthase

Produces glutamate from glutamine and alpha-ketoglutarate
Only bacteria and plants
Together with glutamine synthase leads to assimilation
Does not use ATP
2 Glutamate yield: Can enter glutamine synthetase reaction
Only in plants and microorganisms

10

Glutamine

Acts as amino group carrier
Synthesis in peripheral tissues and transport to liver also transports amino groups

11

Amino acids

Protein monomeric units
Energy metabolites: can be converted into pyruvate, oxaloacetate, or TCA intermediates
Some can only be converted into acetyl CoA, ketone bodies or fatty acids
Precursors for many biologically active nitrogen-containing compounds
Signalling molecules
Essential and non-essential

12

Essential amino acids

Must be taken up with diet

13

Non-essential amino acids

Can be synthesized by body
Plants and microorganisms have enzymes for the synthesis of all 20 amino acids

14

Transamination

Catalyzed by aminotransferase (transaminase)
Reaction with alpha-ketoacid to yield another amino acid and alpha-ketoglutarate

15

Transaminase

All have pyridoxal phosphates as prothetic group

16

Pyritical phosphate

Derived from pyridoxine VitB6

17

Aspartate aminotransferase

alpha-ketoglutarate + aspartate = glutamate + oxaloacetate

18

Malate-Asparate shuttle

Relies on transamination of aspartate and oxaloacetate
Indirectly transfers NADH into mitochondrial matrix
Malate in exchange for KG, Asp in exchange for Glu

19

Amination/deamination

Catalyzed by glutamate dehydrogenase in mitochondrial matrix
Degradation of amino acid to give KG: reversible
Direction determined by reactant concentrations

20

Amidation

Formation of amide bond: irreversible
Glutamine synthetase converts glutamate + NH4+ to glutamine
Costs ATP

21

Deamidation

Catalyzed by glutaminase
Conversion of glutamine to glutamate
Reverse of glutamine syntheses reaction

22

Amino acid synthesis

Animals synthesize from intermediates of glycolysis and citric acid cycle
Bacteria and plants synthesize with sulfur, branched chains, aromatic groups, histidine, lysine and threonine

23

Cysteine synthesis

Can be made from methionine
Not sufficient: essential aa

24

Glutamate formation

From KG by reductive lamination or transamination
Neurotransmitter in brain: conversion to glutamine prevents overstimulation and neurotoxicity

25

Glutamine-glutamate shuttle

In brain
Neurons secrete glutamate as NT: too much extracellular is toxic
Astrocytes (surrounding neutrons) take up glutamate and convert it to glutamine
Glutamine is secreted and taken up by neurons and converted back

26

Aspartate

Synthesized from oxaloacetate by transamination
Asparagine, methionine, threonine, lysine and isoleucine are synthesized from aspartate

27

Asparagine synthetase

Synthesizes aspartate into asparagine

28

Serine

Derives carbon skeleton from glycolytic intermediate 3-phosphoglycerate
Served from 3-phosphoglycerate via dehydration, transamination and hydrolysis
Precursor for sphingolipids and phospatidylserine
Enantiomer D-serine is neuromodulator

29

Glycine

Hydromethyl group transfer reaction from serine
Neurotransmitter

30

Cysteine

Serine plus sulphur group from another amino acid
Thiol group is redox active
Precursor for glutathione

31

Glutathione

Antioxidant
Tripeptide of glutamate of cysteine and glycine
Cysteine is lease abundant: supply is rate limiting
reacts with peroxide to give non-reactive thiols
GSSG in oxidized form

32

One-Carbon metabolism

Describes metabolic pathways that are connected to reactions involving the transfer of single carbons: methyl groups of different oxygen states equivalent of methanol, formaldehyde and formate
Includes folate metabolism, methylation cycle and transsulfuration
Most important carriers of 1-C groups: folic acid and S-adenosylmethionine

33

Folic Acid

B vitamin (B9)
Once absorbed by the body, converted to tetrahydrofolate (THF)
One of most important carriers of 1-C groups
Very important during development
Decreased prevalence of neural tube defects following folate fortification of flour

34

S-adenosylmethionine

Derivative methionine
One of most important carriers of 1-C groups

35

Tetrahydrofolate

Synthesized from folic acid/folate/vitamin B9, requires NADPH
Carrier of 1-C units in several reactions of amino acids and nucleotide metabolism: carrier of methyl groups in different oxidation states
Accepts methyl group from serine to convert serine to glycine

36

Serine hydroxymethyltransferase

Catalyzes transfer of methyl-group from serine to tetrahydrofolate to convert serine to glycine

37

Folate metabolism

Required for serine to indirectly supply methyl groups for methionine synthesis, B6 and B12 are also required
Methylation requires 3 phosphates

38

Methionine synthase

Works with B12
Synthesizes methionine from homocysteine by taking methyl group from 5-methyl-THF to convert it to THF

39

Methionine

Converted from homocysteine by accepting methyl group from 5-methyl-THF
Converted into S-adenosyl-methionine by using 3 phosphates

40

S-adenosyl-methionine

Converted from methionine
Methylated into S-adenosyl-homocysteine

41

S-adenosyl-homocysteine

Addition of H2O and release of adenosine to give homocysteine

42

DNA methylation

Methylation of cytosine to 5-methyl cytosine
Catalyzed by DNA transferases
Regulates transcription without changes in DNA sequence

43

Epigenetics

DNA methylation

44

Importance of methylation reactions

DNA methylation (epigenetic)
Phosphatidylcholine synthesis (from phosphatidylethanolamine)
Thymidine synthesis (dTMP from dUMP)
Purine synthesis
Synthesis of carnitine, creatine, epinephrine and other products

45

Amino acids and signalling molecules

Glutamate and glycine as neurotransmitters
Other neurotransmittedrs/neuromodulators derived form amino acids
Catecholamines
Nitric oxide

46

GABA

NT derived from glutamate

47

Dopamine

From tyrosine

48

Serotonin

From tryptophan

49

Melatonin

From tryptophan

50

D-Serine

NT
By racemizaton of L-serine

51

D-aspartate

NT
By racemizaton of L-aspartate

52

Catecholamines

Epinephrine, norepinephrine, dopamine
Derivatives of tyrosine

53

Nitric Oxide

From precursor arginine

54

Nitric oxide synthase

Reacts with arginine and NADPH and oxygen to citrulline, NO, NADP+ and water

55

Purine synthesis

AMP and GMP
Requires glutamine, glycine, aspartate, bicarbonate and methyl groups
ATP promotes GMP synthesis
GTP promotes AMP synthesis: two purine will be present in roughly equal amounts

56

Pyrimidine synthesis

UMP and CMP
Requires glutamine, aspartate, bicarbonate
dUMP is methylated to generate dTMP
CTP inhibits pyrimidine synthesis (negative feedback)
ATP is feedforward activator for pyrimidine synthesis

57

Deoxyribonucleotide synthesis

ATP, GTP, CTP and UTP are dephosphorylated, then reduced to deoxyribonucleotides by ribonucleotide reductase and phosphorylated again: requires NADPH

58

Ribonucleotide reductase

Reduces dephosphorylated ATP, GTP, CTP and UTP to deoxyribonuceotides
Two regulatory sites: 1 to regulate overall activity, and one to regulate substrate specificity (overall synthesis and relative amount of the different dNTP)
Activated by ATP
dATP decreases activity
Binding of purine ATP: reductase prefers pyrimidines
Binding of pyrimidine dTTP: reductase prefers purine GDP

59

Protein degradation

By proteasome or lysosomal proteases
Each protein has a biological half-life
Most amino acids are degraded to precursors for gluconeogenesis: carbon skeleton of amino acids resemble energy metabolites and can be oxidized for energy

60

Lysosomes

Internal vesicular organelles that have very low pH
Contain many different proteases
Usually takes place after endocytosis of extracellular and membrane material
Intracellular material and whole organelles can also be packaged into large double-membrane vesicles which fuse with lysosomes for degradation: autophagy

61

Autophagy

Intracellular material and whole organelles can be packaged into large double-membrane vesicles which fuse with lysosomes for degradation

62

Proteasomal degradation

Breaks down single proteins
Proteins are tagged with small 76aa protein ubiquitin and degraded by large multi protein complex proteasome
Important quality control mechanism: breaks down misfiled and damaged proteins

63

Both glycogenic and ketogenic amino aicds

Isoleucine
Phenylalanine
Threonine
Tryptophan
Tyrosine

64

Ketogenic amino acids

Leucine
Lysine

65

Branched chain amino acids catabolism

First two steps for all are transamination and decarboxylation
BCKD

66

Maple Urine Syrup Disease

Caused by defects in BCKD

67

Degradation of aa carbon skeleton

Carbon skeleton of glycogenic amino acids are used for pyruvate of TCA cycle intermediates: useful for anaplerosis and glucogneogenesis
Of ketogenic amino acids: converted to acetyl-CoA energy substrate but not for gluconeogenesis or anapldrotic reactions

68

Negative N balance

Nin less than Nout
Starvation
Serious illness
Insufficient essential amino acids

69

Postitive N balance

Nin less than Nout
Growth
Pregnancy
Recovery illness or starvation

70

Excretion of excess nitrogen

Amino acid transamination does not eliminate nitrogen form the body
Some reactions set free ammonium, which can be directly eliminated form the body
High ammonium concentrations are cytotoxic (especially for the brain)
Terrestrial animal secrete nearly 80% excess N as urea
Some eliminated as ammonium salts or uric acid
Purines are broken down to uric acid

71

Lysine

Only amino acid that cannot be transaminated

72

Urea

Highly water soluble
Non-Toxic
pH neutral
Eliminates two amino groups per molecule urea
Highly efficient nitrogen disposal
Terrestrial animal secrete nearly 80% excess N as urea
Direct precursor is arginine

73

Arginine

Direct precursor of urea
Intermediate in urea cycle

74

Direct substrates of urea cycle

Aspartate and carbamoyl phosphate

75

Products of urea cycle

Urea and fumarate
Fumarate is covered to oxaloacetate through TCA cycle reactions

76

Carbamoyl phosphate synthesis

Investment of energy to generate a transferable amino group
Controls urea production

77

Carbamoyl phosphate synthetase

Controls the urea cycle and is activated by N-acetylglutamate: controls urea production

78

N-acetylglutamate

Allosteric activator
Formed when degradation of amino acids lead to high concentration of acetyl-CoA and glutamate

79

Urea

Formed from cyclic pathway in liver
Intermediates are not used up
One amino group stamps from ammonia, one from aspartate, carbon comes from bicarbonate
Enters blood stream and is filtered out by kidney into urine: requires large quantities of water to be excreted