Assorted Need to Knows Flashcards
glycolysis reg
glucose to glucose-6-phosphate through hexokinase (most tissue) or glucokinase (liver)
substrate/product reg
fructose-6-phosphate to fructose 1,6-bis-phosphate via PFK-1. Not reversible, now committed. Inhibitted by ATP, activated by ADP. MOST IMPORTANT. bypassed in fructose metabolism
PK makes pyruvate, which can then become lactate under anaerobic conditions
PDH
- Pyruvate Dehydrogenase
- Decarboxylates w/ TPP
- Redoxs w/ FAD and NAD
- acyltransfers w/ (lipoate), CoA (pantothenic acid)
a. PDHK inhibits
b. PDHP activates (Ca)
c. PDH deficiency: lactic acidosis, neuro problems
Proton Uncouplers
DNP & Salycillic acid
CPT1
CPT I is a major regulator of fatty acid catabolism. Malonyl CoA is an allosteric inhibitor of CPT I. Insulin and AMP regulate the production of malonyl CoA.
MCAD deficiency
A relatively frequent inborn error of metabolism in people of northwest European ancestry is medium chain acyl CoA dehydrogenase deficiency (MCAD).
Infants present with: Reye syndrome fasting hypoketotic hypoglycemia hepatic encephalopathy sudden infant death syndrome
Diagnosed by:
lipid profile in blood
identification of mutations
Prognosis:
If identified before severe hypoglycemic episodes, not bad. Fasting tolerance improves with age.
rate limiting step in fatty acid synth
In the first step of fatty acid synthesis, cytoplasmic acetyl CoA is converted to malonyl CoA by the addition of carbon dioxide. Acetyl CoA carboxylase catalyzes this reaction, using biotin as a cofactor.
This reaction is the rate limiting step in fatty acid synthesis, and is regulated in multiple ways:
Citrate allosterically activates (feed forward)
Insulin increases transcription
Xylulose 5-phosphate increases transcription
Insulin stimulates dephosphorylation, activating the enzyme
Palmitoyl CoA allosterically inhibits (product)
Phosphorylation by AMP-PK inhibits
Glucagon cAMP PKA inhibitory phosphorylation
Malonyl CoA inhibits carnitine palmitoyl transferase I, preventing β-oxidation of newly synthesized fatty acids.
key AAs
a. Glutamate → a-ketoglutarate [intracellular N pool]
b. Asparatate → Oxaloacetate [Transfer to Urea Cycle]
c. (cortisol instructs breakdown) Alanine → Pyruvate [gluconeogenesis]
d. Glutamine →Glutamate (→ Arginine / Proline ) [transfer to liver]
e. Serine: one carbon donor in folate pool, forms ceramide (for gangliosides), can be phosphorilated
- Branched Chain AA diseases
a. Maple Syrup Urine Disease
b. Branched chain aa degraded to Acetyl CoA, blocks this enzyme
c. Treatable subtype of Autism
d. A kinase phosphorylates BCAA a-ketoDh, led to decrease in BCAA, led to autism
PKU
A defect in phenylalanine hydroxylase prevents tyrosine biosynthesis.
Phenylalanine accumulates in the brain and blood. Tyrosine becomes an essential amino acid.
Symptoms: Infants are normal at birth, and gradually develop seizures, cognitive delay, light complexion, “mousy” odor (from phenylacetate).
Diagnosis: All infants born in the US are screened for blood phenylalanine and tyrosine concentrations using tandem MS/MS.
Treatment: Phenylalanine restricted diet.
Methotrexoate
inhibits FH2 to FH4
SAM
methyl donor
gout
GMP and AMP are degraded to xanthine, which is oxidized to uric acid by xanthine oxidase.
Purine degradation can lead to hyperuricemia, which is usually subclinical. However, uric acid is not very soluble, and purine degradation can lead to precipitation of uric acid in the distal joints. This condition is gout.
Treatment is to add allopurinol, which allosterically blocks the production enzymes
nucleotide recycling diseases
a. SCID = Adenosine Deaminase = very low lymphocytes skeletal problems
b. CID = Purine Nucleotide Phosphorylase = Failure to Thrive
c. Lesch-Nyhan = Hypoxanthine-Guanine Transferase = Self-Mutilation
cholesterol metabolism enzyme
HMG CoA reductase
When cholesterol is abundant, the transcription factor sterol response element binding protein (SREBP) is sequestered in intracellular membranes in complex with SREBP cleavage activating protein (SCAP).
When cholesterol levels drop, SCAP cleaves the DNA binding domain of SREBP, which then translocates to the nucleus and regulates transcription of HMG CoA reductase.
statin also inhibitsc.
Glucagon through AMPK inhibits
Congenital adrenal hyperplasia
mutation in steroid hormone biosynthesis genes, e.g. Cyp21. In these patients circulating aldosterone and cortisol are decreased, and androgens are increased.
HDL function
a. Acid ApoE and ApoCII to Chylomicrons (Apo48) and VLDL (Apo100)
b. Familial Hypercholesterolemia = LDL receptor deficiency
fructose problems
i. Essential Fructosuria (Fructokinase)
ii. Hereditary Fructose intolerance (Aldolase B), bad, fuctose-phosphate builds up
c. Galactosemia
i. Galactokinase = non-classic = cataracts
ii. Transferase = Classical = FTT, Jaundice
iii. Epimerase = Benign; only WBC and RBC affected; Galact restricted diet
pentose phosphate pathways
a. 2 Purposes
i. NADH+, H+
ii. 5C Sugars
b. 2 Phases
i. Oxidative
ii. Regenerative: Transketolase & Transaldolase
- X-5-P as Txn Regulator
a. Glucagon, ChREBP, Glucose→acCoa→malonyl Coa→FA Synth
c. Glucose-6-Phosphate Dehydrogenase Deficiency
i. Ox Stress
ii. Favism
iii. Glutathione can’t reduce ROS
- Cyclic Arach Acid Pathway vs Linear Arach Acid Pathway
- Cyclic Arach Acid Pathway → Prostaglandins (PIG2 & TXA2)
3. Linear Arach Acid Pathway → Leukotrienes (bronchioconstriction & athsma)
- PGI2 vs. TXA2
a. PGI2
i. Decreased platelet agg
ii. Vasodilation
b. TXA2
i. Inc Platelet agg
ii. Vasoconstriction
endocannabinoids
Endocannabinoids bind CB1 receptors receptors in nerve synapses, resulting in an analgesic effect.
They also bind a peripheral cannabinoid receptor, CB2, which is present in the spleen and immune cells.
Lactose synthase
Normally, galactosyltransferase acts as a monomer to attach galactose to glycoproteins.
The α-lactalbumin subunit is upregulated after parturation and provides substrate specificty for glucose.
o vs n
In O linked glycosylation, glycosyltransferases add nucleotide conjugated sugars from a pool in the lumen of the endoplasmic reticulum.
In N linked glycosylation, branched chains of sugars are assembled on dolichol phosphate, an organic molecule that is embedded in the ER membrane. An entire chain is transferred to a protein, then modified to its final structure.
VD
plasma concentration over time helps calculate this
malaria
open K channels, then opens Na channels, then cell goes boom
hyaluronic acid
the core of proteoglycan aggregates
cystic fibrosis and Cl flow
reduces it
collagen
1: ordinary
2: hyalin
3: loose, vessels, dermis, placenta
4: basement membrane
5: widespread
5-FU
inhibits thymidylate synthase
eosinophil
allergies, worms
mast cell
tissue resident, inflamation
neutrophil
1st responders
macrophage
long term
Igs
A: mucous
G: delayed, fixes complement
M: immediate response
E: mast cells and basophils, allergies
basophil
histimine, lymph nodes
Th
0: Blast T cell
1: cell mediated response
2: humoral response
17: inflamation
Reg: antigen specific inhib
IL
1: pyrogen
2: teaches T-cells
4: stims IgE
6: pyrogen
10: modulates inflammatory response
12: T cell differentiation
OTC is
sex-linked
