Ketogenic amino acids are transferred to either acetyl CoA or acetoacetate. Glucogenic amino acids are transferred into pyruvate of TCA intermediates (oxaloacetate, alpha-ketoglutarate, succinyl CoA, fumerate)
Maple Syrup Urine Disease
Deficiency in branched chain alpha keto acid dehydrogenase (this enzyme is very close in structure to PDC, B6, B1, and folate are essential for function). Presence of branched chain amino acids and their alpha keto derivatives in the urine, gives maple syrup smell. Accumulation in blood as well causing toxic effects on brain function and mental retardation. Eating a diet low in branched amino acids should help treat this as well as consuming thiamine (B1)
SAM functions as a methyl donor for various reactions, such as norepinephrine to epinephrine, DNA methylation, THF to N-methyl THF, and more.
What enzyme converts Homocysteine to Cystathionine
Cystathionine beta synthase. Requires PLP (B6)
What enzyme converts Homocysteine to Methionine
Homocysteine methyltransferase, with the help of Folate (THF)
What enzyme associated with maple syrup urine disease is used to break down branched amino acids
Branched Chain alpha keto acid dehydrogenase.
What coenzyme is used with phenylalanine hydroxylase, tyrosine hydroxylase, triphosphate 5-monooxygenase and converts DHB to THB
Dihydrobiopterin Reductase. It oxidizes NADPH in the process
What enzyme converts Homogentisate to Maleylacetoacetate.
Homogentisate oxidase. A defect in this enzyme is associated with Alkaptonuria.
The body can't convert dopa to dopamine and so the brain lacks this neurotransmitter. This can be treated by administering L-Dopa (not dopamine because dopamine cannot base the blood brain barrier).
This enzyme is responsible for converting Tyrosine to Melanin. Defects in this enzyme cause Albinism.
Acetaminophen overdose effect on Glutathionine
Glutothionine is used to detox cells and protect them from free radicals. It is also used to conjugate hydrophobic drugs such as acetaminophen to a more polar state. Acetaminophenoverdose can lead to a decrease in Glutothionine which can be harmful to the body, especially the blood.
Increased serum levels of AST (SGOT) typically means....
Increased serum levels of ALT (SGPT) typically means....
Damage to the liver, such as hepatitis, or prolonged circulatory collapse.
Used to activate amino acids. Utilizes an ATP to connect Amino Acids onto the tRNA
Transfers the oligosaccarhide from dolichol, an ER imbedded isoprenoid, to the newly synthesized protein
Types and Locations of Lipophilic Signals
They are located in the cytoplasm or in the nucleus or nuclear membrane. Usually DNA binding transcription factors are the effectors
Types and location of Hydrophilic Signals
Within the cytoplasm of the cells, Typically integrated proteins. Usually G-proteins.
Guanine Exchange factor. In G-protein pathway, the receptor acts as GEF and allows the g-protein to release GDP and grab GTP (when the receptor and G protein are associated after ligand has been bound).
Ligand binds receptor. G protein binds to intracellular portion of receptor. Receptor acts as GEF and G protein exchanges a GDP for GTP. This causes G protein to dissociate subunits and activates G alpha then activates Adenylyl Cyclase. AC converters an ATP to cAMP which binds to PKA which is made up of 4 subunits. cAMP binds to the two inhibitory subunits and now the other two subunits are available to phosphorylate other proteins. Meanwhile, after G-alpha has activated AC, it then converter GTP into GDP and is inactive again.
Cholera toxin targets the G-protein. This keeps G proteins in the GTP active state (it cannot dephosphorylate GTP). This keeps the G-protein in the active state. cAMP production increases 100 fold. cAMP actives PKA which activates CFTR. This receptor causes the cell to pump out Cl-, which causes the cell to secrete water.
Remove signal molecule (eg. phosphodiesterases degrade cAMP)
Remove receptor (eg. receptor removed in endosome
Remove and degrade receptor (eg. endosome to lysomes)
G-protein receptor kinases. These phosphorylate the third domain of the G protein receptor. Arrestin then binds to the receptor. Therefore GDP bound G proteins cannot be activated. This leads to desensitization.
IP3, DAG, and Ca 2+ messengers
Instead of adenyl cyclase, G proteins activated Phospholipase C. This converts IP2 to IP3 and creates DAG. IP3 then binds to the ER and releases Ca2+. DAG and Ca 2+ bind to Protein kinase C (PKC), which can phosphorylate other membrane or cystolic proteins
Ras Independent and Dependent pathway
The ras dependent pathway has Grb2 bind to ras and activate the Map kinase system. That leads to changes in gene expression.
The ras independent pathway has PI 3 kinase which leads to protein phosphorylation and causes a change in protein and enzyme activity
First discovered oncogene. Part of Grb2 protein. Activated by binding to the tyrosine kinase domain of Tyrosine kinase receptor. SH2 then binds to RAS, activating it. RAS plays a large role in cell division.
What is downstream of RAS
Ras binds to Raf, which then causes a cascade of phosphorylation. The next proteins that are activated are, MAP kinase kinase kinase, then MAP kinase kinase, then MAP kinase. This leads to moving past the restiction point in cell cycle.
Jak Stat Receptor Pathway
2 Receptors binds ligand. They dimerize, and bind Jaks (enzyme). The Jaks phosphorylate one another and the cystolic domain of the recepter. The receptor binds STATs which are phosphorylated. They then dissociate and dimerize. Then translocate to the nucleus.
RB and E2F
Retinoblastoma binds to E2F to inactivate. Once Retinoblastoma is phosphorylates and remove by cyclin D CDK4 and 6 (important in moving past restriction point) E2F can activate gene transcription of cyclin E so the cell can transition from G1 to S phase and also cyclin A so S phase can occur. Retinoblastoma is a tumor suppressor gene.
Cyclin CDK pathway
CDK is inactive until it binds cyclin. CDK is inactivated by T-loop. Once cyclin bind, t-loop backs out of the activation site and CDK is partially activated. Next, CDK activating kinase (CAK) phosphorylates CDK and now it is fully active.
Inhbits the CDK-Cyclin complex by phosphorylating the roof site.
Removes the phosphate off of Cyclin and CDK to activate it.
Inactivates the Cyclin CDK complez. In the CIP/KIP family. CDK inhibitor proteins.
This is activated by binding to Cdc20. Together this complex will attach ubiquiton to the Cycylin CDK complez, marking it for degradation. Their main target is Synthesis cyclins and mitosis cyclins. This is required to move from metaphase to anaphase (depends on protein degradation).
When DNA is damaged, protein kinases phosphorylate p 53, which in turn leads to an increase in transcription of p21, which inactivates cyclin CDK complex. MDM2 keeps p53 inactive. This is relevant for checkpoint G1.
Four major classes of cyclins
G1 cyclin (D): Hlps the passage of cells through the restriction point in late G1 phase. Cyclin D-CDK4 complex and Cyclin D-CDK6 complex
G1/S cyclin (E): Helps the cells at the end of G1 phase to commit to DNA replication and enter S phase. Cyclin E-CDK2 complex
S phase cyclin (A): Necessary for the initiation of DNA synthesis. Cyclin A-CDK2 complex
M phase cyclins (A and B): Necessary for the nuclear division during mitosis. Cyclin A-CDK1 complex and Cyclin B-CDK1 complex
Required for full activation of the Cyclin CDK complex. This phosphorylates CDK.
Extrinsic Pathway for Apoptosis
Fas bind to Fas receptor of the cell. This allows for the intrinsic portion of the receptor to recruit FADD proteins which form a homotrimer with their death domains. This will also bring along procaspase -8 which will then be activated and cause a cascade to activate caspase-3 that will lead to apoptosis.
Intrinsic Pathway for Apoptosis
Mitochondria relases cytochrome c. Cytochrome c activates procaspase activating adaptive protein called Apaf1. Apaf1 combines with other activated apaf1's to create apoptosome. This then activates caspase 9 which will cascade and activate caspase 3.
This process is activated by BAX and inhibited by BCL
Virus infects host. RNA is reverse transcribed into DNA and integrated into the host genome. It accidentally incorporates an adjacent host proto-oncogene into its genome. It converts protooncogene into an oncogene. The virus cantaining the oncogene can now transform normal cells and cause tumors. V-src is a tyrosine kinase that has been mutation and turned into an oncogene. v-src is the oncogenic form of the normal host proto-oncogene called c-src.
v-Src is oncogene c-Src is proto oncogene.
Deletion in the chromosome 15 q 11-13 subsection. This causes mental retardation, ataxia, uncontrolled laughter, seizers. UBE3 deletion in mother. None produced in child because it is methylated in the paternal chromosome.
Deletion in the 15 q 11-13 subsection. This causes mental retardation, hypotonia, obesity, short stature, small hands and feet. This is caused by a deletion in the male chromosome. The female chromosome is methylated at SNRP and therefore will not produce it. So no SNRP is produced leading to this disease
One example of monosomy that actually produces a living offspring. Usually result in short stature and webbed necks.
47,XXY. Considered males but phenotypically are both m and f
Trisomy 13, Patau syndrome: Cleft palate and bilateral lip, low-set malformed ears, hypoterlorism and postaxial polydactyly of the left hand.
Trisomy 18, Edwards Syndrome: Clenched fist, short sternum, narrow pelvis, hypertelorism, short palpebral fissures, and rocker bottom feet.
Trisomy 21, Down syndrome. Mental retardation and pronounces forehead. reduced bridge of nose.
Cornelia De Lange syndrome
Mutation in cohesion of Chromosomes. Causes Thin upper lip with down turned mouth corners, short nose, hair across bridge of nose or synoferous. Cleft pallet. Small hands. Usually develope with portions of the limbs missing. Usually severely retarded.
Zona or Cortical Reaction
Fast phase - the resting potential of the oocyte changes preventing spermatocyte binding.
Slow phase - oocyte releases granules containing enzymes to degrade the sperm receptor proteins (zp3)
Spermatocyte entering into the Oocyte
Zp3 receptor of sperm binds to Zp3 of egg. This causes more receptor in sperm to gather around binding site. Acrosome releases acrosins which eat their way into the egg. Zp2 receptor keeps sperm attached. Once the membranes of the sperm and egg fuse, granules are released and prevent egg from binding more sperm.
When the blastocyte implants somewhere other than the uterus. This can be caused by the synticiotrophoblast eats through the uterus wall and continues to eat through connectiive tissue and muscle.
Fetal contribution to the placenta. It is the trophoblast with the extracellular mesoderm.
What do we by the 3rd week of pregnancy
3 layers: Synctiotrophoblast, cytotrophoblast, and extracellular mesoderm.
3 cavities: Amniotic space, Yolk sac, and chorion.
Visceral, internal organs.
Wall of body cavity (skeletal muscle)
Cyclooxygenase (COX1 or COX2)
This enzyme binds to Arachnidonic Acid or related PUFAs and converts it to PGH2 (or prostaglandin endoperoxide). Cyclooxygenase contains Fe and uses O2 as a cofactor in order to carry out this conversion.
Cox 1 is constitutive.
Cox 2 is inducible. Exception in the renal system because it requires large response. Cox 2 is not made in platelets.
This liberates Arachnidonic Acid from the phospholipid bilayer. AA can then be converted into prostaglandins or thromboxane
Converts PGH2 into PGF2 alpha, PGE2, or PGD2.
TX Synthase of PGI Synthase
This converts PGH2 into either PGI2 or TxA2. Vary among tissues
15 OH PG Dehydrogenase
This converts PGD, PGE, F2 alpha in to the inactive PG
Autacoids respond to localized stimuli. PG and thromboxane are not hormones. They are autacoids because they are short lived. They are quickly metabolized by 15 OH PG Dehydrogenase or degraded. Cells that use PGs are acting in a paracrine or autocrine fashion
Eicosanoid that binds to receptor in the Vasculatrue or endothelium. Also Renals. Typically causes muscle relaxation (vasodilation) and reduces platelet aggregation in the blood vessels. In renal, it causes sodium and water excretion.
Binds to these systems.
Vasculature: Causes Permeability
GI (Gut): Increases Mucosalcytoprotection, Muscle tone, Motility
Renal: Sodium and Water excretion
Uterus: Muscle contraction
CNS: Temperature PNS: Pain Sensitization
Binds to blood platelets. Causes vasoconstriction and blood platelet aggregation.
Binds in uterus. Causes muscle contractions.
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