SYLLABUS 14: Amino Acid Metabolism - General Introduction

Question 1

recommended amt of protein in the human diet?

Answer 1

75-2100 g/day

= 300-400 Kcal of energy/day

= 15-20% of our caloric intake

Question 2

where does protein digestion occur

Answer 2

begins in the stomach, is completed in the GI tract

Question 3

essential vs non essential amino acids?

Answer 3

essential: those that can’t be synthesized by us and most mammals; must be provided in the diet

nonessential: can be synthesized by us, from carbohydrate precursors and a source of nitrogen - ammonia or alpha amino group of other amino acids

Question 4

name the essential amino acids

Answer 4

*PVT TIM HALL *

P: Phenylalanine

V: Valine

T: Tryptophan

T: Threonine

I: Isoleucine

M: Methionine

H: Histidine

A: Arginine (children/growth!)

L: Lysine

L: Leucine

Question 5

name the non-essential amino acids

Answer 5

Glut

Gln

Ala

Gly

Ser

Asp

Asn

Pro

Tyr* (comes from Phe)

Cys* (comes frm Met & Ser)

Question 6

what is nitrogen balance?

Answer 6

if amount of nitrogen consumed, mainly in form of protein = amount of nitrogen excreted, mainly as urea

Question 7

when does positive vs negative nitrogen balance occur?

Answer 7

POSITIVE balance: Dietary N > Excreted N; growth - childhood, pregnancy

NEGATIVE balance: Dietary N < Excreted N; illness, infection, catabolic stress, inadequate intake of protein in the diet, or intake of protein diet deficient in essential amino acids

Question 8

what’s unique about Tyr and Cys?

Answer 8

they’re nonessential amino acids made from essential amino acids

Tyr is from Phe

Cys is from Met & Ser

Question 9

functions of amino acids?

Answer 9

1. synthesis of new protein for growth and repair
2. replace damaged protein
3. synthesize regulatory enzymes per metabolic conditions

Question 10

what sorts of metabolites do amino acids produce?

Answer 10

near all nitrogenous metabolites found in the body, including:

purine and pyrimidine rings of the ntds

heme

GSH

hormones

neurotransmitters

creatine

Question 11

what do amino acids in excess provide/become?

Answer 11

energy

per degredation to pyruvate, acetyl CoA, TCA cycle intermediates, ketone bodies

Question 12

how do amino acids interact w/ gluconeogenesis and FA metabolism?

Answer 12

aa are a critical source of carbon for gluconeogenesis

aa can be used to produce fatty acids

Question 13

do we have a storage form of aa?

what is result of this?

Answer 13

no

excess aa are made into C atoms which acn be stored as triglycerides or glycogen

however aa also have Nitrogen, amino, group - which become NH4+, ammonia, which is v. toxic

thus must get rid of ammonia, which is via urea, excreted in urine via urea cycle

Question 14

function of transamination rxns?

result?

Answer 14

allow removal of the alpha amino group from an amino acid, or allow transfer of an alpha amino group from an amino acid to an alpha-keto acceptor

result: production of a new aa from the alpha keto acceptor & a new alpha keto acceptor from the original aa

Question 15

what is the GOT reaction

Answer 15

aspartate aminotransferase reaction aka glutamic-oxalacetic transamination reaction

transamination

glutamate + oxalacetate -> a-KG + aspartate

Question 16

what is the GPT reaction?

Answer 16

alanine aminotransferase or glutamic pyruvate transaminase reaction

transamination

glutamate + pyruvate -> a-KG + alanine

Question 17

nature of transamination rxns?

Answer 17

reversible!

most use glutamic acid/a-KG as 1 of the exchange partners

can use non-essential amino acids as long as glutamic acid is available, along w/ C sources (OAA, pyruvate for ex)

Question 18

what would happen if found GOT in a patient’s bloodstream?

Answer 18

would know there is tissue damage b/c GOT was released from tissue -> bloodstream

Question 19

what is PLP?

what’s it derived from?

Answer 19

pyridoxal phosphate

cofactor of all transaminases, and many other enzymes involved in amino acid metabolism

it’s derived from Vitamin B6, Pyridoxine

Question 20

method of a transamination reaction?

Answer 20

2 half reactions:

1st half reaction: a-amino group from donor aa is transferred to the PLP cofactor, which is at active site of the transaminase, forming a-keto acid and pryidoxamine P. cofactor changes from an aldehyde to an amine

**2nd half reaction: **1st a-keto acid product dissociates away from the active site, & is replaced by a new a-ketoc acid; pyridoxamine cofactor transfers the amino group to pyruvate, which becomes alanine; PLP form of cofactor is regenerated, stays attached to ransaminase for another cycle

alanine product dissociates away from active site, new substrate aa, glutamate, enters to repeat rxn

Question 21

what is a schiff base linkage?

Answer 21

linkage produced between alpha amino group of an amino acid + PLP cofactor at the acive site of enzymes metabolizing amino acids

Question 22

what reactions produce schiff base linkages?

Answer 22

reactions involving aa metabolism - transamination, decarboxylation, racemization, modifications of the side chains of aa

Question 23

what is nature of the linkages surrounding a schiff base

Answer 23

all can be broken depending on the reaction + the enzyme

Question 24

what happens to schiff base in a transamination

Answer 24

bond between the alpha amino group and the alpha carbon of the incoming amino acid is eventually hydrolyzed

this results in amino group hanging on to the cofactor as pyridoxamine P and formation of the alpha keto acid

Question 25

what happens to schiff base in a decarboxylase reaction?

Answer 25

eg histdine -> histamine

bond between the alpha carbon and the alpha carboxyl group is broken, resulting in release of Co2 and decarboxylated former amino acid, which is not an amine

cofactor: vitamin B6

Question 26

cofactor of carboxylases?

Answer 26

biotin

Question 27

what happens in racemase reaction w/ a schiff base?

Answer 27

bond between alpha carbon and alpha hydrogen is labilized - results in a change of congiuration around the alpha carbon - so from D-aa to L-aa or vice versa by moving alpha C from 1 side to the other

Question 28

what happens in a dealdolase reaction re: schiff base?

Answer 28

bond between the alpha carbon and R group is labilized, result in release of R group

i.e. serine to glycine by taking off CH2OH

Question 29

how can aa be used as a source of energy

Answer 29

AA can be used as a source of energy if they are in excess; in such conditions, AA are
degraded to pyruvate, acetyl CoA, TCA cycle intermediates, and ketone bodies. AA also
are a source of C for gluconeogenesis and can be used for FA synthesis.

Question 30

why do proteins have such diff turnover rates

Answer 30

s the rate at which old proteins are degraded
and new proteins are made to replace them. The question is very broad, but just asks
you to think about why some proteins need to be replaced daily and others may last for
weeks or years.

Question 31

what is transamination

why is it important

what is significant of GOT or GPT in clinical medicine or in diagnosis

Answer 31

Transamination is a reaction that removes the a-amino group from an AA.

Usually
involves an a-amino acid and a-keto acid with a cofactor including PLP, whereby the
amino group from the a-amino acid is transferred to an alpha keto acid acceptor,
producing a new AA from the a-keto acceptor and a new a-keto acceptor from the
original AA.

GOT or GPT in the blood would indicate tissue damage

Question 32

4 basic reactions invovling amino acids which require pyridoxal phosphate as a cofactor?

what is fate of aa group in each?

Answer 32

4 basic reactions involving AA that require PLP as a cofactor are: racemase;
decarboxylase; modifications to amino acid side chains; and transamination.
a. Transamination: alpha amino group ends up on the cofactor
b. Decarboxylase: alpha amino group stays attached to the a-carbon, producing a
decarboxylated former AA, now amine
c. Racemase: Change in configuration from D to L; amino group thus remains attached
to the alpha C of the original AA
d. Dealdolase: Alpha amino group remains attached to AA alpha carbon