you can’t make an alpha-ketoacid analog of it because its long side-chain NH2 will lead to a Schiff Base cyclization product named pipecolic acid:
here are a few pages from a copyrighted book about transamination:
the urea cycle February 29, 2008
ok i think i get it. i think i get it. i think i get it.
first, amino acids with N’s you want to get rid of are transaminased into glutamate, essentially a common denominator for nitrogen trashing. once you get there, the glutamate needs to be transported into the liver for the cycle:
this cycle occurs in two compartments. the mitochondrial compartment handles the rate-limiting step of carbamoyl-P synthetase, while the cytoplasmic compartment handles the generation of urea from arginine.
think of carbamoyl-P as the temporary N-carrier that gets the N from the mitochondria to the cytoplasm. it is manipulated and piggybacks off of ornithine, the most important molecule in the cycle. it joins with aspartate, which has another N to spare. finally these 2 Ns ends up in arginine, which arginase I will cleave to generate a urea (with 2 N equivalents). whew. interestingly, the urea cycle is only complete in the liver, BUT arginase II isozymes exist in other organs (the kidney). so if arginase I fails, the arginine can travel in the bloodstream to the kidney for completion of the urea cycle.
carbamoyl-P synthesis is regulated by a byproduct of glutamate combining with acetyl-CoA, N-Acetylglutamate (NAG).
urea is disposed of in the kidney or in the gut. bacterial ureases cleave urea into NH3 and CO2. the majority of this NH3 is reabsorbed back in the large intestine (doh!). so this isn’t the most efficient way to get rid of ammonia.
urea cycle defects lead to hyperammonemia, with toxication signs of altered mental status, tremors, cerebral edema, and blurred vision. you can treat this by reducing protein in the diet or sterilizing the gut, which gets rid of the bacterial ureases that would normally regenerate reabsorbable NH3.
branched chain amino acid metabolism February 29, 2008
how does the liver take complex branched chain amino acids (BCAA’s: leucine, isoleucine, and valine) into usable amino acid fuels? by using the muscle.
huh? the muscle does something other than contract? yep, by the following transamination reaction:
- glutamine is an almost exclusive fuel for enterocytes.
- alanine participates in a cycle similar to the Cori cycle:
- valine, a BCAA, is actually used in the CNS to generate myelin
ketone bodies February 28, 2008
ketone bodies an alternate product to acetyl-CoA metabolism. if you’re in a fasting state, hypoglycemic, or diabetic, your body may switch from using carbohydrates to fatty acids. the product of beta-oxidation is acetyl-CoA, which can be converted to ketone bodies in the liver and the kidney. ketone bodies are then distributed in the blood system, primarily to the brain and to the heart.
the major ketone body is beta-hydroxybutyrate. it just so happens that beta-hydroxybutyrate is also a good way to get rid of excess NADH that may have been generated elsewhere (such as in excessive alcohol intake or a backed up ETC).
unfortunately, the accumulation of ketone bodies can also be a bad thing, since beta-hydroxybutyrate is acidic and can lower your blood pH. you can detect this by smelling a patient’s breath. the fruitier, the ketone-ier.
mitochondrial electron carrier shuttles February 28, 2008
NADH and FADH2 are generated by glycolysis, the TCA cycle, and beta-oxidation. products of glycolysis and the TCA cycle are generated within the cytoplasm, and cannot freely enter the inner mitochondrial membrane (IMM). instead, elaborate shuttle systems have been designed on the backs of IMM integral proteins to transfer electrons so they can access the electron transport chain.
the main system is the malate-aspartate shuttle.
malate is transported across the IMM, where it is oxidized, using NAD+ as an oxidizing agent and generating a matrix NADH. aspartate is the product. this is then transported back into the intermembrane space. here, it is reduced back to malate using NADH as a reducing agent, and regenerating the NAD+ used in the matrix.
an ancillary system is the glycerol phosphate shuttle. this is used less because its electron transfer is less efficient than the malate-aspartate shuttle. instead of regenerating an NADH, this shuttle converts an NADH (2.5 ATP’s worth) to FADH2 (1.5 ATP’s worth) via DHAP and glycerol-3-phosphate redox cycles:
lastly, FADH2 doesn’t actually need to be shuttled. it’s a moiety that is actually a prosthetic group within complex II, which contains succinyl dehydrogenase. since the only step in FADH2 production is within the Krebs Cycle, there is never a need to shuttle FADH2 in.
lastly, beta-oxidation occurs within the IMM, so the NADH and FADH2 generated from fatty acids do not need to be shuttled to the electron transport chain.
hyperlipidemia February 26, 2008
hyperlipidemia, or dyslipidemia, results from abnormal levels of cholesterol or triglycerides in blood. one definition is total cholesterol, LDL, triglyceride, or Lp(a) levels in the 90th percentile.
primary causes are metabolic disorders that are often familial: 
- type 1 hyperchylomicronemia is an excess of chylomicrons, caused by defective VLDL (abnormal ApoCII) or LDL (decreased LpL activity) synthesis backing up liver processing of chylomicrons
- type 2a hypercholesterolemia is an excess of LDL, caused by an inability to dock with cells (abnormal LDL receptor binding to ApoB100)
- type 2b combined hyperlipidemia is an excess of VLDL (excessive VLDL secretion from increased ApoB100 activity) and LDL (decreased LDL receptor), representing a combination of type 2a and type 4
- type 3 dysbetalipoproteinemia is an excess of VLDL and IDL, caused by abnormal remnant reuptake (defective ApoE, lacking in LDL)
- type 4 hypertriglyceridemia is an excess of TG-carrying VLDL
- type 5 mixed hypertriglyceridemia is an excess of TG-carrying VLDL and chylomicrons, representing a combination of type 1 and type 4 (1+4=5), whereby decreased LpL activity leads to an excess of chylomicrons that can still be converted into an excess of VLDL
secondary causes include:
- type 2 diabetes mellitus from insulin resistance increasing cholesterol and TG levels
- cholestatic liver diseases (ex: primary biliary cirrhosis) that cause backed up Lipoprotein X
- nephrotic syndrome leaking proteins that drop the oncotic pressure, causing a compensatory rise in liver lipoprotein synthesis
- chronic renal failure from diminished clearance
- hypothyroidism from decreased LDL receptors (normally regulated by T4 levels)
- cigarette smoking
- obesity
- drugs
clinical manifestations include:
- atheromata
- xanthoma (especially eyelid and tendinous)
- corneal arcus
sources:
- uptodate.com
- First Aid 2007
- wikipedia.com
- Hyperlipidaemia: Diagnosis and Management
