Protein V Flashcards
How do we obtain creatine?
Diet from animal products
What reaction does creatine participate in?
Creatine participates in one reaction. It is phosphorylated by creatine kinase to yield creatine phosphate (or phosphocreatine)
What is creatine phosphate used for?
Serves as energy reserve in muscle and some other tissues. Can be used to phosphorylate ADP, generating ATP
What is the role of creatine phosphate in energy metabolism?
In skeletal muscle,
ATP concentration high in resting muscle - phosphorylation of creatine by creatine kinase is favored
During exercise, muscle ATP is depleted rapidly - Creatine kinase uses creatine phosphate as a phosphate donor in phosphorylation of ADP to regenerate ATP
How is creatine synthesized by the liver?
Glycine and arginine are used to create guanidinoacetate and ornithine through L-arginine:glycine amidinotransferase
Guanidinoacetate is converted to creatine via guanidinoacetate methyltransferase
What is the relationship between creatine and creatinine?
Creatine is released from muscle cells and excreted via the urine.
Over 90% of creatine is found in skeletal muscle.
Daily production of creatinine depends on skeletal muscle mass and is excreted entirely by the kidneys
What indicates kidney impairment?
Sudden changes in serum creatinine
How do patients present with inborn errors of creatine metabolism? What causes these errors?
Defects in creatine synthesis and uptake
Children present with hypotonia but little skeletal or cardiac muscle pathology
Variety of neurological symptoms
What are important signaling molecule derived from tyrosine?
Dopamine
Norepinephrine
Epinephrine
Where does sequential modification of tyrosine occur and what are those cells?
Occurs in catecholamine producing cells:
Dopaminergic Neurones - Dopamine
Sympathetic neurones - Norepinephrine
Adrenal medulla - epinephrine
How is dopamine formed from tyrosine?
Tyrosine is hydroxylated by tyrosine hydroxylase with THBtn to produce DOPA.
DOPA is then converted to dopamine via DOPA decarboxylase
How is norepinephrine formed from tyrosine?
Tyrosine forms dopamine and then dopamine is made into epinephrine via dopamine Beta-monooxygenase and vitamin C
How is epinephrine formed?
Tyrosine forms dopamine. Dopamine forms norepinephrine. Norepinephrine then forms epinephrine via norepinephrine N-methyltransferase
Parkinsonism
Progressive degeneration of dopaminergic neurones. Usually affects people over 60 and relief found through administration of DOPA
What other molecules are produced from tyrosine?
Iodinated derivative of tyrosine - T3 and T4, thyroxine
Melanin
How are thyroid hormones produced from tyrosine?
Tyrosine is iodinated by thyroid peroxidase in thyroglobulin.
Thyroid peroxidase then couples iodinated tyrosine resides together
Proteolysis of thyroglobulin releases thyroid hormones
Where is melanin produced and how is tyrosine converted to melanin?
Synthesized in Golgi of melanocytes
Absorbs in UV region of spectrum
Tyrosine converted to dopaquinone via tyrosinase. Metabolism of dopaquinone then yields black/brown or yellow/red melanin
Melanin passes from melanocytes to keratinocytes
What is black/brown melanin?
Eumelanin - provides protection from UV radiation
What is yellow/red melanin?
Pheomelanin
Albinism Type 1 (OCA1)
Patient presents with white hair, unpigmented skin, and irides that appear pink
Oculocutaneous albinism type 1 (OCA1)
Complete loss of function of tyrosinase so not able to synthesize melanin in skin, hair, and eyes. Patient will have impaired vision and appearance of skin tumors
What are 3 special products derived from tryptophan?
Serotonin
Melatonin
Niacin
What is important about serotonin and how is it produced from tryptophan?
Serotonin is important signaling molecule and is abundant in platelets and in GI tract. Found in brain and retina.
Tryptophan undergoes hydroxylase reaction with THBtn and then the aromatic product is decarboxylated to serotonin
How is melatonin derived from tryptophan?
Tryptophan produces serotonin. Serotonin converted to melatonin in pineal gland, which responds to light/dark cycle. Melatonin produces sleep
How is niacin derived from tryptophan?
Liver generates niacin from tryptophan, which is catalyzed by IDO.
IDO emerging as anticancer drug target/
What is a vitamin deficiency that leads to pellagra?
Niacin deficiency. Diets low in niacin, tyrptophan or the cofactors requires for enzymes of niacin synthesis can all lead to pellagra
What is Hartnup disease?
Occurs when uptake of amino acids from blood and reabsorption by kidney is blocked
Treated with high protein/niacin diet
What are important products made by decarboxylation?
GABA - derived from decarboxylation of glutamate, important neurotransmitter
Histamine - decarboxylation of histidine and produced in mast cells involved in allergic reactions
What is glutathione?
Tripeptide with sequence of Glu-Cys-Gly and synthesized mainly by liver and very stable because of gamma-glutamyl linkage
What is important about glutathione?
Important intracellular reducing agent. Scavenging free radicals and destroys peroxides. When oxidized, forms dimer GSSG
Plays important role in drug detoxification and generates thioether linkage between compound and cysteine of glutathione
Rich in red blood cells, reducing peroxides formed during oxygen transport
What does glutathione peroxidase and reductase do?
Glutathione peroxidase - catalyzes reduction of peroxides
Glutathione reductase - regenerates glutathione, using NADPH as a reducing agent
What is chlorambucil?
DNA alkylating agent used in treatment of various malignancies like leukemia - metabolized by glutathione transferases
