Amino acids synthesis and metabolism

Ways to get energy

● Energy which occurs in the form of ATP can be gotten from acetyl CoA through the TCA cycle.

● Sources of acetyl CoA : – Beta oxidation of fatty acids

– Pyruvate by the action of PDC

– Amino acids metabolism

PS: PDC is the pyruvate dehydrogenase complex

Steps to exploit amino acids

1)Deamination

2)Oxidative decarboxylation ( production of CO2 and NADH )

3)Dehydrogenation (that resembles betta oxidation to some point).

methods of deamination

Transamination

● Definition : transfer of amine from amino acid to be utilized to a ketoacid ( alpha ketoglutarate or oxaloacetate) by the enzyme aminotransferase (transaminase) which Needs pyridoxine (B6) as a cofactor

● All amino acids can undergo transamination except lysine ● Safest way because amine NH3 is a non-soluble toxic molecule

● A.A. + alpha ketoacid →alpha ketoacid + aspartate/ gulatamate

PS: if OAA is used then the product is aspartate however if alpha ketoglutarate is used then the product is glutamate

Oxidative deamination

● The amine is extracted as a free NH3 by the enzyme oxidase

● This method includes the reduction of FMN to FMNH2

Non oxidative dehydration

● By the enzyme dehyratase ● It involves the removal of free NH3 from the

amino acid● Just for the amino acids : serine and threonine

Disorders in Amino acid metabolism

PKU

● Deficiency in phenylalanine hydroxylase which leads to deficiency in the degradation of phenylalanine and synthesis of tyrosine

● The phenylalanine is transformed to phenylactate and phenylpyruvate

Alkaptonuria

● Deficiancy in the enzyme that oxidize the homogenistic acid intermediate in the catabolism of tyrosine and phenylalanine so the oxidation of this intermediate in the urine leads to its black color

Maple syrup urine disease (MSUD)

● Involves a mutation in the decarboxylase enzyme that convert the alpha keto acid ( of the LIV amino acids ) to acetyl COA

● Leads to accumulation of ketoacids and then to ketoaciduria

LIV : leucine isoleucine and valine

Syntehsis of amino acids

● Synthesis of the carbon skeleton first ( ketoacid) then the addition of ammonia

● Some backbones can be synthesized => non essential whereas others can't be synthesized and should be supplied by the diet => essential

Essential amino acids

● TV TILL PM HA ?● T: threonine and tryptophan ● I: isoleucine ● L: leucine lysine ● P: phenylalanine ● M: methionine ● H : histidine ● A: alanine

Nonessential that come from essential aa

● The sulfur of non essential cysteine comes from methionine

● Tyrosine is synthesized from phenylalanine

Role of amino acids :

● Building block of protein ● Energy ● Excitatory neurotransmitters : aspartate and

glutamate ● Inhibitory neurotransmitters ● Precursors of neurotransmitters● Hormones

Glucogenic / ketogenic / both

Glucogenic aminoacids Amino acids

Keto acids + glutamate/ aspartate

OAA

fumarate/proprionyl CoA/ketoglutarate/ pyruvate

glucose

PEP

AAA CC GGG HM PSV

● Asparginine● Arginine● Alanine

● Cysteine ● Cystine● Glycine

● Glutamic acid● Glutamine● Histidine

● Methionine● Proline● Serine● Valine

Ketogenic

Oxidative decarboxylation

Acetyl coA/ aetoacetate

dehyrogenation

Amino acid

PS : acetyl CoA and ketone bodies join the TCA cycle without being carbon donors for oxaloacetate ( disappear AS 2 co2)

LEUCINE LYSINE

both

● Gives both glucogenic and ketogenic precursors

● Phenylalanine● isoleucine ● Tyrosine● Tryptophan● threonine

Regulation of Urea cycle

● Regulation of synthesis of N acetyl glutamate the cofactor of CPS1 by arginine concentration ( directly proportional )

● Protein diet stimualte the enzymnes of urea cycle● Acidosis leads to removal of NH3 as NH4+ instead as

urea so the cycle is inhibited ● In case of fasting amino acids are degraded and more

amine are produced so the cycle is stimulated

Regulation of amine in blood

● Glutamine is a buffer for amine● The respective transformation between different

forms containing different number of amine regulate amine concentration in blood either release or absorb

glutaminase Glutamate DH

Glutamine synthetase transaminase

Glutamine(2 NH3)

Ketoglutarate (no NH3)

Glutamate (1 NH3)

Nitrogen balance

● Neutral (excreted = taken) ● Positive(excreted < taken) in growing or

regenerating cells so more protein is synthesized ● negative(excreted > taken) in case of protein

malnutrition or fasting so that some un-necessary aa are degraded to be utilized later on in producing other important aa or energy so more NH3 is produced