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.
