lipid metabolism-ketogenesis

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LIPID METABOLISM- ketogenesis:

LIPID METABOLISM- ketogenesis Dr. Hariharan , V Assistant professor, Department of Biochemistry, Karpagam Faculty of Medical Sciences and Research, Coimbatore. Free ppt available in www.authorstream.com/ search drhari

What are ketone bodies:

What are ketone bodies Acetone Acetoacetic acid Beta hydroxy butryic acid Free ppt available in www.authorstream.com/ search drhari

When ketone bodies produced:

When ketone bodies produced Metabolic conditions associated with high rate of fatty acid oxidation, the liver produces ketone bodies Free ppt available in www.authorstream.com/ search drhari

Ketogenesis :

Ketogenesis FFA ATP CoA Acyl CoA Synthetase Acyl CoA Esterification TAG Phospholipid Beta Oxidation Acetoactyl CoA Acetyl CoA TCA cycle HMG CoA Synthase HMG CoA HMG CoA Lyase Acetoacetate 3-OH butyrate Thiolase 3-OH butyrate Dehydrogenase NAD + NADH + H +

Steps :

Steps Two acetyl CoA formed in Beta oxidation joins to form acetoacetyl CoA by Thiolase . Acetoacetyl CoA is also obtained from terminal 4 Carbons of Acyl CoA during beta oxidation Acetyl CoA combines with Acetoacetyl CoA to form HMG CoA by HMG CoA synthase HMG CoA Lyase removes Acetyl CoA to form Acetoacetate Acetoacetate can interconvert to Beta hydroxy butyrate by 3-hydroxy butyrate dehydrogense using NAD. This enzyme is controlled by NAD/NADH ratio Free ppt available in www.authorstream.com/ search drhari

Provision of energy by ketone bodies:

Provision of energy by ketone bodies Acetoacetate produced by the liver is taken up by extrahepatic tissues and converted into Acetoacetyl CoA by Succinyl Acetoacetate CoA transferase . Succinyl CoA donates CoA Acetoacetyl CoA converted to acetyl CoA by thiolase and it enters TCA cycle to produce energy Beta hydroxy butyrate produced by liver is also taken up by extrahepatic tissues and converted to Acetoacetyl CoA and to acetyl CoA to produce energy Free ppt available in www.authorstream.com/ search drhari

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Regulation of ketogenesis:

Regulation of ketogenesis 1. During starvation, insulin level decreases and glucagon level rises. The change in insulin/Glucagon ration stimulates adenylyl cyclase  increased cAMP in adipose tissue stimulates hormone sensitive lipase excess degradation of TAG to FFA increased FFA influx to liver. Free ppt available in www.authorstream.com/ search drhari

Regulation ….:

Regulation …. 2. After entry into liver, FFA are either undergoes beta oxidation or ketone bodies or reesterified to form TG. CPT-I level is low in fed state, so FA oxidation is inhibited In starved state, CPT-I activity is high, so Beta oxidation is stimulated. Malonyl CoA inhibits, CPT-I. As more FFA enters liver, Acyl CoA inhibits Acetyl CoA carboxylase ( Malonyl CoA formation), so the end result  CPT-I stimulated  Beta oxidation stimulated Also in starvation, Insulin/Glucagon ratio decreasesinhibition of acetyl CoA carboxylase  stimulation of Beta oxidation Free ppt available in www.authorstream.com/ search drhari

Regulation….:

Regulation…. 3. Acetyl CoA has two fates. Either entering TCA cycle or Ketogenesis . - During starvation more acetyl CoA enters Ketogenesis because, TCA cycle cannot handle too much Acetyl CoA from the fatty acids because of the limits of ETC coupled with oxidative phosphorylation Free ppt available in www.authorstream.com/ search drhari

Ketosis:

Ketosis The normal levels of ketone bodies is <1mg/dl When ketone bodies levels exceeds this limit, leads to ketonemia and ketonuria . Overall it is called ketosis It occurs in Starvation Diabetic ketoacidosis High fat feeding Severe exercise in the postabsorptive state Von Gierke’s disease Free ppt available in www.authorstream.com/ search drhari

Starvation:

Starvation Insulin/ Glucagon ratio decreases  activates lipolysis and inhibits Acetyl CoA carboxylase leading to ketogenesis Free ppt available in www.authorstream.com/ search drhari Diabetic Ketoacidosis Here glucose is not available to peripheral tissues and insulin is low  lipolysis and ketogenesis

Features of Ketosis:

Features of Ketosis Metabolic acidosis: Beta hydroxy butyrate and Acetoacetate are acids--. Causing acidosis Kussmaul breathing- metabolic acidosis leads to hyperventillation  acetone is evaporated in breath fruity odor Ketonuria  osmotic diuresis  dehydration Diagnosis: Rothera’s test for acetone/ acetoacetate in urine Gerhadt’s test for acetoacetate Ketostix ketone bodies level in blood Free ppt available in www.authorstream.com/ search drhari

Treatment:

Treatment Treat the cause- starvation, Diabetes Bicarbonate Plenty of fluids oxygen Free ppt available in www.authorstream.com/ search drhari

References:

References Harper Vasudevan Tietz Free ppt available in www.authorstream.com/ search drhari

PowerPoint Presentation:

Free ppt available in www.authorstream.com/ search drhari Thank you

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