Amino Acid Metabolism

Front 1

Dietary protein contains _____ standard amino acids and several non-standard amino acids that are mostly derived by ________ modification such as hydroxyproline, gamma-hydroxylysine and gamma-carboxy-glutamate.

Back 1

20 standard amino acids

post-translational modifiation

Front 2

Standard amino acids from the diet are used in what 2 ways?

Back 2

1) Protein synthesis

2) energy metabolism

Front 3

___ of 20 standard amino acids are ______, which means they must be supplied in the diet.

Back 3

10

essential

Front 4

____________ gets rid of the alpha amino group. ________ is often used - it accepts the alpha-amino group from other acids and donates its keto group, producing glutamate and an alpha-keto acid.

Back 4

Transamination

alpha-ketoglutarate

Front 5

__________ facilitates deprotonation of the alpha-carbon by resonance stabilization of the _______.

Back 5

pyridoxal-phosphate (PLP)

stabilizes the carbanion

Front 6

________ mediates the transfer of nitrogen between various amino/alpha-keto acids.

Back 6

Glutamate

Front 7

______ prevents depletion of alpha-ketoglutarate.

Back 7

Glutamate dehydrogenase

Front 8

________ scavenges residual ammonia before blood re-enters general circulation following the urea cycle.

Back 8

glutamine synthetase

Front 9

Serine dehydratase removes ______, NOT water.

Back 9

ammonia

Front 10

Phenylketonuria results from a homozygous defect of ________.
The phenylalanine makes _______, which has neurotoxic metabolites.

Back 10

phenylalanine hydroxylase

phenylpyruvate

Front 11

Doctors used to test babies for phenylketonuria with the _____ Test. This test used PHE- ___ bacteria that could only grow when Phe was present in the blood sample.

Back 11

Guthrie test

PHE- E. coli

Front 12

2 amino acids that act as transmitters.

Back 12

Glycine

Glutamate

Front 13

Some amino acid derivatives acts are transmitters or hormones. Name 4 key amino acids transmitters can be derived from.

Back 13

Tyrosine
Glutamate
Histidine
Tryptophan

Front 14

Name the transmitters/hormones that can be derived from the following amino acids:

Tyrosine

Glutamate

Histidine

Tryptophan

Back 14

Tyrosine - dopamine, NE, E, triiodothyronine, tetraiodothyronine (catecholamines)

Glutamate - GABA (gamma-aminobutyrate)

Histidine - Histamine

Tryptophan - serotonin (5-HT), melatonin

Front 15

Evolutionary perspective on hormones and transmitters:

Need for hormones and transmitters arose with the development of ______. Communication needs a sending and _______ end. Sensory systems for amino acids were already in place and were used from comunication. The ______ was varied to separate roles in communication and in metabolism.

Back 15

multicellular organisms

communication needs a sending and sensing (receiving) end

chemical structure was varied

Front 16

Functions and locations of catecholamines:

dopamine and NE are _____ in the _____

epinephrine and NE are _____ in the ______

Back 16

dopamine and NE are neurotransmitters in the nervous system

NE and E are hormones in the suprarenal gland

Front 17

Effects of catecholamine hormones on circulation:

Heart rate _______.

Heart contractility ________.

Arterial blood pressure ______.

Blood from redistributed from ______ to ______.

Back 17

Heart rate increases.

Heart contractility increases.

BP increases.

Blood flow redistributed from visceral organs to muscle.

Front 18

Effects of catecholamine hormones on metabolism:

Glycogen breakdown ____, synthesis ______.

Gluconeogenesis ____.

TAG breakdown _____.

Back 18

Increased glycogen breakdown, slowed synthesis.

Increase gluconeogenesis.

Increased TAG breakdown.

Front 19

Degeneration of ___ nerve cells in the _______ is responsible for Parkinson's disease. ______ is used for therapy since dopamine itself can't enter the brain from the blood.

Back 19

dopaminergic nerve cells

brain stem

L-DOPA

Front 20

4 locations of amino acid and peptide transporters are?

Back 20

1) in the intestine (from food)
2) kidney (re-uptake from primary filtrate)
3) brain (traversal of the blood brain barrier)
4) any body cell (from interstitial fluid)

Front 21

Kidney _________ gets rid of excess protons. There are ____ and ____ transporters in kidney tubules.

Back 21

kidney glutaminase

Na+ and NH4+ transporters in tubular epithelial cells

Front 22

What is the main site of amino acid metabolism?

Back 22

The liver.

Front 23

How can glutamate and aspartate be synthesized?

Back 23

From their widely distributed a-keto acid precursors by simple 1-step transamination reactions.

These are catalyzed by glutamate dehydrogenase and aspartate aminotransferase respectively.

Aspartate is also derived from asparagine through the action of asparaginase.

Front 24

What is the purpose of the glucose alanine cycle?

Back 24

The urea cycle happens in the liver but the skeletal muscle is also very active in degrading amino acids. Alanine carries nitrogen from the skeletal muscle to the liver to get rid of it.

Front 25

Alanine is formed from _____ by ______ in the _____ tissues. It travels through the blood to the liver, where the nitrogen is abstracted by _______ back to _____, which then enters ________ to regenerate glucose to be sent back to the periphery.

Back 25

pyruvate;
transamination;
peripheral tissues;
transamination;
pyruvate;
gluconeogenesis

Front 26

Contrast the glucose alanine cycle and nitrogen transport via glutamine in terms of energy costs.

Back 26

Transport by glutamine doesn't cost any ATP . The glucose alanine cycle is costly - for every nitrogen transported, 2 ATP are used since 4 moles of ATP are consumed in gluconeogenesis and glycolysis.

Front 27

How is glutamine produced in the peripheral tissues?

What is the second product of this reaction?

Back 27

Conversion from glutamate by GOGAT - glutamine oxoglutarate gamma-aminotransferase (aka glutamate synthase)

This enzyme produces an amide group, not an amine.

The second product is alpha-ketoglutarate, which can then be transaminated.

Front 28

What happens to glutamine produced in the periphery?

Back 28

It travels through the blood to the liver, where the amido group is released as ammonia by glutaminase. The glutamate that results goes back to the periphery.

Front 29

Alanine, aspartate and glutamate all require _________ to become 'mainstream' metabolites.

Back 29

transamination

Front 30

Glutamine and asparagine must be ______ by ______ and ______ respectively, then transaminated.

Back 30

deamidated
glutaminase, asparaginase

Front 31

The formation of ________ occurs in the degradation of serine.

Back 31

Glycine

Front 32

Degradation of ____ and ____, both non-essential amino acids, is the prime source of _________ in metabolism. They are bound to _______, which donates them for use in rxns like the biosynthesis of _______.

Back 32

glycine and serine

single-carbon units (C1-units)

coenzyme tetrahydrofolic acid

nucleotides.

Front 33

3 routes of serine degradation.

Back 33

1) conversion to pyruvate by serine/threonine dehydratase in the liver

2)cleavage into glycine and formaldehyde by serine hydroxymethyltransferase

3)transamination to hydroxypyruvate, which is reduced to glycerate and phosphorylated to 3-phosphoglycerate

Front 34

What coenzyme does serine/threonine dehydratase use to degrade serine? What enzymes is its mechanism similar to?

Back 34

pyridoxalphosphate (PLP) - same as the transaminases

transaminases

Front 35

Why is it preferable for serine degradation by serine/threonine dehydratase to occur in the liver?

Back 35

because ammonia is released as ammonia but not by transamination - the liver can dispose of the ammonia

Front 36

What happens to the formaldehyde that results from serine hydroxymethyltransferase cleavage of serine?

Back 36

It's highly reactive so it is not released but immediately fixed onto coenzyme tetrahydrofolic acid.

Front 37

What is the advantage of the pathway involving transamination of serine to hydroxypyruvate?

Back 37

The 3-phosphoglycerate that is produced can serve as substrates for gluconeogenesis with the advantage that no free ammonia is released.

Front 38

All three routes of serine degradation involve ______ as the coenzyme. In all cases, the reversible transfer of _______ to the coenzyme stabilizes the substrate; the particular bond to be broken is determined by the point of attack of side chains in the enzyme's ________.

Back 38

PLP - pyridoxalphosphate

an electron

active site

Front 39

How can glycine serve as a substrate in gluconeogenesis?

How many glycines for one molecule of pyruvate?

Back 39

The serine degradation reaction with serine hydroxymethyltransferase is reversible, so glycine can be converted to pyruvate or 3-phosphoglycerate via serine. This requires N,N'-methylene-THF to be provided by the glycine cleavage system, so a total of 2 glycine molecules would be required to give one molecule of pyruvate.

Front 40

___________ breaks down glycine completely, using PLP in its catalytic mechanism. One methylene groups is extracted as ________________.

Back 40

Glycine cleavage system

N,N'-methylene-THF

Front 41

Where does most of the degradation of leucine, isoleucine and valine occur?

What's a collective term for these three a.a.s?

Back 41

In the skeletal muscle.

Branched-chain amino acids.

Front 42

6 steps in leucine degradation.

Back 42

1)transamination by branched chain amino acid (BCAA) transaminase to yield alpha-ketoisocaproate

2)decarboxylation & dehydrogenation of alpha-ketoisocaproate by BCAA dehydrogenase to produce isovaleryl-CoA

3)isovaleryl-CoA is similar to fatty acyl-CoA & undergoes FAD-dependent dehydrogenation to yield isopentenyl-CoA

4) Biotin-dependent carboxylation to methylglutaconyl-CoA

5)hydration by methylglutaconyl-CoA hydratase to HMG-CoA

6) HMG-CoA is plit by HMG-CoA lyase to acetyl-CoA and acetoacetate (as in ketone body synthesis)

Front 43

Pyruvate dehydrogenase, BCAA dehydrogenase, and alpha-ketoglutarate dehydrogenase all use the same ____________.

Back 43

E3 subunit

Front 44

6 step degradation of phenylalanine/tyrosine. (know the first 2 and last step)

Back 44

1)hydroxylation to tyrosine by phenylalanine hydroxylase

2)transamination of tyrosine to p-hydroxyphenylpyruvate

3)change of hydroxyphenylpyruvate to homogentisate using vitamin C as a cofactor

4)ring cleavage using 3rd O to maleylacetoacetate

5)maleylacetoacetate is cis-trans isomerized to fumarylacetoacetate

6) fumarylacetoacetate is hydrolyzed to fumarate and acetoacetate

fumarate is Kreb's intermediate, acetoacetate is a ketone body

Front 45

Hydroxylation of phenylalanine to tyrosine by phenylalanine hydroxylas is disrupted in ____.

Back 45

Phenylketonuria

Front 46

Where does the O2 go in the hydroxylation of phenylalanine?

Back 46

One O is part of the -OH on tyrosine, the other is released as water. The H in the water came from the redux cosubstrate Biopterin-H4.

Front 47

What is a Schiff base?

Back 47

A functional group that contains a carbon-nitrogen double bond where the N is connected to an alkyl or aryl group but not H.

Schiff intermediates are formed by PLP in transamination - they allow α-amino groups to be shuttled between amino acids and ketoacids by resonance stabilizing the carbanion.