Exam 2- Amino Acid Metabolism Flashcards
Glucogenic amino acids
Metabolized to pyruvate, 3-phosphoglycerate, alpha-KG, OAA, fumarate, or Succinyl CoA
Ketogenic amino acids
Metabolized to acetyl CoA or acetoacetate
Essential amino acids
Amino acids that humans can’t synthesize
Pvt Tim Hall
Phenylalanine, Valine, Threonine, Tryptophan, Isoleucine, Methionine, Histidine, Arginine, Leucine, Lysine
Transamination reaction
An amino acid donates an amine group to a keto acid
Name the mandatory keto acid and an amino acid in the transamination reaction.
Alpha-ketoglutarate - mandatory keto acid
Glutamate - mandatory amino acid
Describe the role of pyridoxal phosphate (vitamin B6) in the transamination reaction.
Pyridoxal phosphate is the coenzyme involved in the transamination reaction.
In this reaction, the amine group is transferred from the amino acid to the coenzyme, which transports it to the alpha-keto acid, forming a new amino acid and regenerating the original coenzyme aldehyde.
Describe the role of glutamine with reference to nitrogen catabolism.
Glutamine is the transporter of excess nitrogen from the tissues to the liver for the Urea cycle
What are the substrates and products of carbamoyl phosphate synthase.
NH4 + HCO3- + 2 ATP —> Carbamoyl phosphate + 2 ADP + 2 Pi
Carbamoyl phosphate synthase I/CPS-1
N-acetylglutamate is a positive affector
Name two cellular compartments where the urea cycle operates.
Mitochondrial matrix and cytosol
Name the allosteric affector of carbamoyl phosphate synthase I
N-acetyl glutamate
Name a drug that is used for treatment of a urea cycle enzyme deficiency
Carbamoylglutamate - Analog of N-acetylglutamate, can also activate CPS-1
In an exercising muscle, name the cycle that utilizes an amino acid & converts it into glucose.
Glucose-Alanine Cycle
In the liver, alanine is converted to pyruvate by Alanine transaminase. When blood glucose is low, pyruvate —> GNG —> glucose!
Name 3 neurotransmitters that are derived from tyrosine
Dopamine
Epinephrine, norepinephrine
Name 3 types of reactions that are involved in producing a neurotransmitter from an amino acid precursor.
Decarboxylation
Hydroxylation
SAM-dependent methylation
Name 3 cathecholeamines
Dopamine
Norepinephrine
Epinephrine
Name the rate-limiting step in the biosynthesis of catecholeamines.
Tyrosine + O2 + THB —> DOPA + DHB
Tyrosine hydroxylase
Name the cofactors that is required for tyrosine hydroxylase.
Tetrahydrobiopterin
Catecholeamine release is stimulated by the neurotransmitter _____________
Acetylcholine
Name two enzymes that are involved in catecholeamine catabolism.
Catecholeamine O-methyltransferase (COMT)
Monoamine Oxidase (MAO)
Name few functions of catecholeamines.
To prepare the body for “fight or flight” response:
Increase cardiac output, glycogen degradation, triglyceride hydrolysis, and release of fatty acids from adipose tissue
Decrease peripheral resistance to blood flow.
Discuss the connection between Parkinson’s disease and dopamine and the drug that is used for patients.
Parkinson’s disease is due to a lack of dopamine synthesis. It can be treated by L-Dopa, a precursor of dopamine that can cross the blood-brain barrier.
Name 2 neurotransmitter compounds derived from tryptophan
Serotonin and melatonin
What is the hormone that is involved in circadian rhythms?
Melatonin
What is the effect of Prozac?
Inhibits reuptake process of serotonin
If you suffer from jet lag, what pathway would you target for drug therapy?
Melatonin
Name the enzyme that catalyzes the formation of histamines.
Histidine carboxylase
Name 3 functions of histamines
Mediate allergic and inflammatory reactions
Vasodilation & drop in BP
Constriction of bronchioles
Stimulates excretion of HCl
What are the substrates and products of glutamate decarboxylase?
Glutamate —> GABA
(E: glutamate decarboxylase)
Requires Pyridoxal Phosphate (vitamin B6)
In general, decarboxylases require the coenzyme _________
Pyridoxal phosphate
L-DOPA is used for ___________ disease treatment
Parkinson’s
Name a synthetic compound that limits serotonin reuptake.
Prozac
Describe pheochromocytoma.
Tumors of chromaffin tissue that produce large amounts of catecholeamines.
Describe the clinical correlation between Huntington’s disease and GABA metabolism.
Low levels of GABA and GABAnergic neurons result in the uncontrolled movements of Huntington’s disease
Melanins are synthesized in ___________
Melanocytes
Tyrosinase deficiency causes _____________
Albinism
Under oxidative conditions, in order to maintain reducing environment inside the cell, which compound is invoked?
Glutathione
Name the methyl group donor compound that is used in the majority of methyl transfer reactions
S-adenosylmethionine (SAM)
Name 2 functions of glutathione.
Maintains protein sulfuhydryl groups in reduced form.
Detoxifies xenobiotics (peroxides and free radicals) in the liver
Nitric oxide is derived from the amino acid _____________
Arginine
Uses THB
Name the substrate and products of acetylcholinesterase
ACh + H2O —> Acetate + Choline
E: Acetylcholine esterase
Explain the action of DIPF on acetylcholinesterase
DIPF is a component of nerve gas. It covalently modifies acetylcholinesterase and knocks the enzyme activity
Name some xenobiotics that inhibit acetylcholinesterase.
Physostigmine
Neostigmine
Name the channel that is opened up by acetylcholine.
Na+/K+ ion channels
Discuss the mechanism of action of nerve gas.
DIPF is a component of nerve gas. It covalently modifies acetylcholinesterase and knocks the enzyme activity.
Excitatory neurotransmitters
Excitatory:
- Acetylcholine
- Aspartate
- Dopamine
- Histamine
- Norepinephrine
- Epinephrine
- Glutamate
- 5-hydroxytryptamine
Name Excitatory and Inhibitory neurotransmitters
Inhibitory:
- Glycine
- GABA
- Taurine
- 4-aminobutyrate
Excitatory:
- Acetylcholine
- Aspartate
- Dopamine
- Histamine
- Norepinephrine
- Epinephrine
- Glutamate
- 5-hydroxytryptamine
Name the 3 stages of nerve transmission:
Resting
Excitation
Termination
What is the action of GABA?
GABA is inhibitory neurotransmitter. Upon binding to its Beta subunits, it increases membrane permeability of postsynaptic membranes to chloride ion. This can lead to hyperpolarization and increased threshold of triggering an action potential.
What is the function of phenobarbital?
Inhibits action potentials when bound to GABA receptors.
Tx for epilepsy
Name the catabolic products of GABA.
Succinate semialdehyde
Succinate
What is an ion-gated channel?
A channel that allows ions to pass through when a neurotransmitter binds to its receptor.
Name 2 ion channels.
Cholinergic nicotinic receptors
GABA receptors
(More generally, Na and K channels)
Diisopropylphosphoflouridate (DIPF) inhibits the enzyme ___________
Acetylcholinesterase
Name two inhibitors of the ACh receptor
Tubocurarine
Alpha-bungarotoxin
Cobra toxin m
Name two linear compounds in the proline biosynthetic pathway.
Glutamate and glutamate semialdehyde
Describe the role of hydroxyprolines?
Collagen stability - stable collagen triple helix
Name the amino acid that is required for selenocysteinyl tRNA synthesis.
Selenocysteine (21st amino acid)
What is the cofactor that is required for phenylalanine hydroxylase synthesis?
Tetrahydrobiopterin (THB)
What enzyme deficiency causes phenylketonuria?
Phenylalanine hydroxylase
Name two disorders of tyrosine metabolism.
Alcaptonuria, Albinism.
What enzyme deficiency causes albinism?
Tyrosinase
Methionine adenosyltransferase catalyzes the synthesis of _______________
S-adenosylmethionine (SAM)
ATP —-> SAM (E: Methionine adenosyltransferase- MAT)
What compound is the precursor for cysteine synthesis?
Methionine
Name a disorder of cysteine metabolism.
Homocystinuria and Cystathionuria
Name the oxidized form of homocysteine
Homocystine - consists of 2 molecules of homocysteine linked together by a disulfide bond
Name the amino acid precursor for NMP synthesis
Tryptophan
Trp —> other steps —> —> niacin —> NMP
Name an enzyme that requires a Vitamin B12 derivative as a coenzyme
Methionine synthase (in converting homocysteine to methionine)
Methyl Malonyl CoA Mutase (converting propionyl CoA to Succinyl CoA)
Name a disorder of branched chain amino acid metabolism.
Maple syrup urine disease (MSUD)
Name the amino acid that is required for carinitine biosynthesis.
Lysine
Name two amino acids that are required for creatine biosynthesis.
Glycine and Arginine
Name the components of folate.
Pterin, PABA, and Polyglutamine
Name 2 active centers of THF.
N5 and N10
Name the 3 reactions that use THF.
Purine synthesis
Thymidine synthesis
Methionine synthesis
Name the amino acid and the vitamin derivative that is required for glycine synthesis.
Serine and THF
Serine + THF —> (E: Serinehydroxy methyl transferase) Glycine + N5-N10-Methylene THF
Name two amino acid degradative pathways that require THF.
Histidine —> Glutamate
Serine —> Glycine
Name two reactions that require Tetrahydrobiopterin as a cofactor.
Phenylalanine (Phenylalanine Hydroxylase) —> THB
Tyrosine (Tyrosine Hydroxylase) —> DOPA
Tryptophan (Tryoptophan Hydroxylase) —> Serotonin
Describe how homocysteine is converted into methionine
Homocysteine —> methionine
Vit B12 derivative; E: Methionine synthase
Lysine is required for the synthesis of _________
Carnitine
Name the vitamin derivative that is required for the prolyl hydroxylase reaction.
Collagen
Vitamin C
Why is the element selenium essential?
Activation of selenocysteine to tRNA
Describe in detail the pathway of SAM and cysteine.
Methionine + ATP —> SAM —> Homocysteine (B6) —> Cystathione (B6) —> Cysteine + alpha ketobutyrate —> Propionyl CoA
Biochemical basis of Phenylketonuria
- Classical PKU is an autosomal recessive deficiency of phenylalanine hydroxylase
- The accumulated phenylpyruvate and phenylketone are excrete in the urine
- Since tyrosine production is affected, all the related compounds that are derived from tyrosine are also blocked (Ex. DA, NE/epinephrine)
- In some individuals biopterin deficiency causes PKU
Biochemical basis of Alkaptonuria
- Deficiency of hemogentisate oxidase results in the accumulation of homogentisic acid
- Upon accumulation, this compound is oxidized into a dark brown polymer and is deposited in joints, causing arthritis
Biochemical Albinism
- Tyrosinase deficiency results in defective melanin production
- Skin is susceptible to the damaging effects of sunlight such as skin cancer
The biochemical basis for Homocystinuria, Cystathionuria, Cystinuria
Issues with the cysteine biosynthetic pathway
- Vitamin B6 deficiency can block overall cysteine synthesis, as two steps in the pathway require B6 as cofactor
1) Homocystinuria:
- Cystathione beta-synthase deficiency causes homocysteine accumulation
- Vitamin B6 (pyridoxal phosphate) deficiency can exacerbate the condition
2) Cystathionuria:
- Gamma-cystathionase deficiency —> accumulated cystathionine for excretion
- Also requires Vitamin B6
3) Cystinuria
- Defect in membrane transport of dietary cysteine through epithelial cell membrane results in the accumulation of cysteine in the urine
Maple syrup urine disease
Defect in catabolism of branched amino acids
Deficiency in branched chain keto acid dehydrogenase
Histidinemia
Deficiency in the enzyme histidase
Histidine + THF —> Uroconate —> Glutamate
Can folic acid be synthesized by humans?
No
What step is inhibited by sulfamethoxazole?
Inhibits the conversion of para-amino benzocaine acid (PABA) —> folic acid
Folic acid synthesis is inhibited by sulfonamides
Only in prokaryotes
The role of folate in relation to one carbon metabolism
Folate —> DHF —> THF (tetrahydrofolate)
With addition of a 1-carbon unit (tryptophan, hisitidine, serine/glycine) —> active folate
active folate —> purines, thymidine, and methionine
Biosynthesis of carnitine
Lysine —> N-trimethyl lysine —> carnitine
E: Methyl transferase, 3SAM
What are some organism specific dihydrofolate reductase inhibitors?
Methotrexate- eukaryotes
Epiroprim (type of trimethoprim)- bacteria
Pyrimethamine - protozoan (amoeba)
DHF (E: Dihydrofolate reductase) —> THF
Trimethoprim, methotrexate, and pyrimethamine inhibits __________
They all inhibit Dihydrofolate reductase !
Methotrexate- eukaryotes
Epiroprim- bacteria
Pyrimethamine- protozoans/amoeba
3 amino acid specific transaminase:
Alanine aminotransferase (ALT): Alanine to pyruvate Aspartate aminotransferase (AST): aspartate into OAA Alpha KG —> Glutamate
Name 3 glial cells and their functions n
Oligodendrocytes: provide mullein sheaths that insulinate axons
Astrocytes: integral parts of synapses, regulate molecules necessary for interneuron communication. Clear most of glutamate and stop neurotransmission. Also release growth factors and can take up other monoamine nt’s (serotonin and dopamine)
Microglia: closely related to macrophages, fight infections, and release inflammatory substances (may damage neurons) in response to injury
ACh is not metabolized by reuptake process. Explain which cell would catabolize the ACh after the action potential.
Astrocytes
Explain the differences between endogenous proteolysis (protein degradation) versus digestion related degradation.
Endogenous proteolysis = ubiquitination —> degradation by proteasome
Digestion related (dietary protein in excess) = proteolysis into amino acids which undergo transamination reactions producing nitrogen. Nitrogen taken to liver by glutamine, and nitrogen are fed into urea cycle and excreted
Normal blood creatine levels
< 1.5 mg/dL
Describe the lactate dehydrogenase catalyzed reaction.
Cori Cycle:
Muscle: Pyruvate —> Lactate (E: LDH-M)
Liver: Lactate —> Pyruvate (E: LDL-L) —> glucose (through GNG)
Glucose then transferred back to the muscle
When lactate accumulates in the blood it is a problem. Why?
This can lead to lactic acidosis, which can cause a decrease in pH and muscle weakness
Explain why vitamin B6 deficiency can cause brain related problems.
Glutamate —> GABA
Other reactions that use B6: Histidine —> Histamine Dopa —> Dopamine Trp —> Serotonin Homocysteine —> Cystathione —> Cysteine
Reactions that use THB
Phenylalanine —> Tyrosine
Tyrosine —> Dopa
Trp —> Serotonin
Arginine —> NO
Describe the biosynthesis of creatine phosphate and its degradation.
Synthesis:
Glycine + Arginine (SAM) —> creatine phosphate (E: creatine kinase)
Degradation:
Creatine Phosphate —> (spontaneous!) creatinine —> excreted through urine!
Which vitamin derivative is required for many of the decarboxylases?
Pyridoxal phosphate
Describe the 3 NO synthases
Endothelium derived: diffuse out of endothelial cells into vascular smooth muscle, activates cytosolic guanylate cyclase which increases cGMP which up regulates PKG —> phosphorylation of smooth muscle contractile proteins leading to relaxation of vascular smooth muscles (vasodilation)
Brain derived:
Receptors for NO in neurons upregulate cytosolic guanylate cyclase increases cGMP which upregulates PKG —> phosphorylates proteins (not well understood)
Macrophage derived:
Stimulated after bacterial infection, NO toxic to bacteria
Biochemical basis for Parkinson’s
Substantial Nigeria degraded —> decreased dopamine
Biochemical basis for depression
Increased serotonin uptake and degradation (less serotonin)
Pheochromocytomas
Tumors that increase production of catecholeamines —> HTN
Huntington’s
Low GABA (inhibitory) leading to uncontrolled movements (chorea)
Normal BUN levels
10-20 mg/dL
Glucose-Alanine Cycle
In low oxygen conditions, alanine is transferred from the muscle to the liver
Alanine is converted to Pyruvate by alanine deaminase in the liver
Pyruvate can then re-enter the GNG cycle
Glucose returned to the muscle
Describe the connection between dicarboxylate and the urea cycle
Fumarate leaves the Urea cycle in the arginosuccinate lyase step which converts arginosuccinate to arginine
Fumarate can enter the dicarboxylate cycle and become aspartate which is necessary for the previous step in which citrulline becomes arginosuccinate using the enzyme arginosuccinate synthase
