Step 1 - Biochem 5

denniskwinn's version from 2015-04-25 15:57


Question Answer
Draw fa synthesis112
Fatty acid synthesisstart with citrate-->citrate shuttle to take it from mito matrix-->cytoplasm, ATP citrate lysase -->acetyl CoA-->(requires biotin) malonyl CoA-->palmitate (16C FA)
Malonyl CoAinhibits carnitine shuttle (FA breakdown) so that FA can be synthesized only
Fatty acid breakdownFatty Acid + CoA-->Acyl CoA via FA CoA synthetase-->thru carnitine shuttle then beta oxidized in mito matrix to ketone bodies and to TCA cycle
Carnitine deficiencyinability to transport LCFAs into the mitochondria resulting in toxic accumulation - causes weakness, hypotonia and hypoketonic hypoglycemia
Acyl-Coa dehydrogenase deficiency↑ dicarboxylic acids, ↓ glucose and ketones
Ketone bodiesIn the liver, fatty acids and amino acids are metabolized to acetoacetate and Beta-hydroxybutyrate (to be in muscle and brain). 2. In prolonged starvation and diabetic ketoacidosis, oxaloacetate is depleted for gluconeogenesis. In alcoholism, excess NADH shunts oxaloacetate to malate, both processes stall TCA cycle which shunts glucose and FFA toward the production of ketone bodies - made from HMG-CoA - metabolized by the brain to 2 molecules of acetyl-CoA - excreted in urine
Fuel in 100 m sprint (seconds)Stored ATP, creatine phosphate, anae robic gl ycolysis
Fuel in 1000m run (minutes)Stored ATP, creatine phosphate, anae robic gl ycolysis and oxidative phosphorylation
Fuel in marathonglycogen and FFA oxidation - glucose conserved for sprinting
Fasting prioritiessupply sufficient glucose to brain and RBCs and to preserve protein
Starvation days 1-3.Blood glucose level maintained by: 1. Hepatic glycogenolys is and glucose release 2. Adipose release of FFA 3. Muscle and liver shifting fuel use from glucose to FFA 4. Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adiposc tissue glycerol and propionyl-CoA from odd-chain FFA metabolism (the only triacylglycerol components that can con tribute to gluconeogenesis)
Starvation after day 3Muscle protein loss is maintained by hepatic formation of ketone bodies, supplying the brain and heart.
Starvation after several weeksKetone bodies become main source of encrgy for brain, so less muscle protein is degraded than during days 1-3. Survival time is determined by amount of fat stores. After this is depleted, vital protein degradation accelerates, leading to organ failure and death


Question Answer
Cholesterol synthesisRate-limiting step is catalyzed by HMG-CoA reductase (converts HMG-CoA to mevalonate) - 2/3 of plasma cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT) - Statins inhibit HMG-CoA reductase
Essential fatty acidsLinoleic and linolenic acids - Arachidonic acid, if linolenic is absent - Eiconasoids are dependent on essential fatty acids.
Draw lipid transport pictures114
Pancreatic lipasedegradation of dietary TG in small intestine
Lipoprotein lipase (LPL)degradation ofTG circulating in chylomicrons and VLDLs
Hepatic TG lipase (HL)degradation of TG remaining in IDL.
Hormone-sensitive lipasedegradation of TG stored in adipocytes.
Lecithin-cholesterol acyl transferase (LCAT)catalyzes esterification of cholesterol.
Cholesterol ester transfer protein (CETP) mediates transfer of cholesterol esters to other lipoprotein particles
Apolipoprotein A-IActivates LCAT.
Apolipoprotein B100Binds to LDL receptor, mediates VLDL secretion.
Apolipoprotein C-IICofactor for lipoprotein lipase.
Apolipoprotein B-48Mediates chylomicron secretion.
Apolipoprotein EMediates extra (remnant) uptake
Lipoproteinscomposed of varying proportions of cholesterol, triglycerides(TGs) and phospholipids. LDL and HDL carry most cholesterol.
Chylomicron function/routeDelivers dietary TGs to peripheral tissue. Delivers cholesterol to liver in the form of chylomicron remnants, which are mostly depleted of their triacylglycerols. Secreted by intestinal epithelial cells.
Apolipoproteins in chylomicronB-48, A-IV, C-II, E
VLDL function/routeDelivers hepatic TGs to peripheral tissue, secreted by liver
Apolipoproteins in VLDLB-100, C-II, E
IDL function/routeFormed in the degradation of VLDL. Delivers triglycerides and cholesterol to liver, where they are degraded to LDL
Apolipoproteins in IDLB-100 and E
LDL function/routeDelivers hepatic cholesterol to peripheral tissues. Formed by lipoprotein lipase modification of VLDL in the peripheral tissue. Taken up by target cells via receptor-mediated endocytosis.
Apolipoprotein in LDLB-100
HDL function/routeMediates reverse cholesterol transport from periphery to live r. Acts as a repository for apoC and apoE (which are needed for chylomicron and VLDL metabolism). Secreted from both liver and intestine
Familial dyslipidemias I - hyperchylomicronemia1. Increased chylomicron 2. Elevated TG, cholesterol, 3. Lipoprotein lipase deficiency or altered apoliprotein C-II, causes pancreatitis, hepatosplenomegaly and eruptive/pruritic xanthomas (no increase in risk for atherosclerosis)
Familial dyslipidemias IIa - familial hypercholesterolemia1. Increased LDL 2. Elevated blood cholesterol 3. Autosomal dominant absent or ↓ LDL receptors. Causes accelerated atherosclerosis, tendon (Achilles) xanthomas and corneal arcus
Familial dyslipidemia IV - hypertriglyceridemia1. Increased VLDL 2. Elevated Triglyceride in blood 3. Hepatic overproduction of VLDL - causes pancreatitis
Abeta-lipoproteinemiaHereditary inability to synthesize lipoproteins due to deficiencies in apoB100 and apo b48, autosomal recessive, symptoms appear in the first few months of life. Intestinal biopsy shows accumulation within enterocytes due to inability to export absorbed lipid as chylomicrons. . Findings: failure to thrive, steatorrhea, acanthocytosis, ataxia, night blindness