TCAGLYCOLYSISGLUCONEOGENESISGLYCOGENESISGLYCOGENOLYSISPPP

What is it for? Provides majority of ATP for energy Gluconeogenesis from skeletons of AABuilding blocks for AA & Heme (succinyl CoA)Breakdown of glucose into 3-C compounds to provide energyProduction of glucose from the following intermediates:1) Intermediates of : glycolysis & the TCA2) Glycerol: from Triacylglycerols3) Lactate: through Cori Cycle4) C skeletons ( ketoacids) of glucogenic amino acidsWELL-FED

Synthesis of new glycogen molecules from -D-glucoseFASTING

Shortening of glycogen chains to produce molecules of a D-glucoseProduction of important intermediates: NADPH provides electrons for: FA & Steroid biosynthesis Reduction of Glutathione CYP450 WBC Respi burst NO synthesis Ribose-5-phosphate Synthesis of nucelotides Metabolic use of 5-C

Where does it occur?In ALL cells with mitochondriaMitochondrial matrix

EXCEPT: succinate dehydrogenase (inner membrane)Cytoplasm (ALL cells) Liver (90%) Kidney (10%) Mitochondria CytoplasmLiverMuscleCytosolLiverMuscleCytosol / CytoplasmCytoplasm

What is/are the substrate(s)?Acetyl CoAGlucosePyruvate1) UDP-glucose2) ATP & UTP3) Glycogenin: core, primer proteinGlycogen

Leaves about 4 glucose residues before a breanch point a limit dextrinG-6-P

No consumption or production of ATP

What is/are the end product(s)? CO2 GTP NADH FADH2Pyruvate or Lactate

Depending on the availability of mictochondria & O2GlucoseGlycogen Glucose-1-P Free glucose

Liver can release free glucose to circulationMuscle Limited to G-6-P within muscle onlyFree glucose Produced during the debranching process Ribose-5-P F-6-P Glyceraldehyde-3-P NADPH

Which step is rate limiting?Isocitrate ketoglutarateF-6-P F-1,6-BPF-1,6-BP F-6-PElongation of glycogen addition of (14) bondsRemoval of glucoseBreaks (14) bondsG-6-P 6-Phosphogluconate

Rate limiting enzymeIsocitrate dehydrogenasePFK-1F-1,6-BisphosphotaseGlycogen synthaseGlycogen phosphorylaseG-6-P dehydrogenase

Diseases Pyruvate dehydrogenase activity Choronic alcoholismHypoglycemiaGlycogen storage diseases

G6PD DeficiencyChronic granulomatous disease

FA synthesis oxidationCholesterol synthesisSteroid hormone synthesis

What is it for?Formation of Palmitate (16:0)Gets Acetyl CoA fragments from the ends of FAsAcetyl CoA can enter the citric acid cycleGenerates NADH & FADH2 that can enter the ETCDe novo synthesis of cholesterolCholesterol is precursor of ALL steroid sex hormones

Glucocorticoids (Cortisol)-without this hypoglycemia in stressful situationsMineralocorticoids (Aldosterone)-fluid regulation-without this HypervolemiaSex hormones (Testosterone & Estradiol)

Where does it occur?CytosolMajor: Liver, Lactating mammary glandsMinor: Adipose tissueMitochondria of almost all cells

Exceptions: NeuronsRBCTestisKidney MedullaVirtuall ALL cells

CytosolSER

Liver & Intestines (majority)SER of:Adrenal cortexOvaries & TestesPlacenta

What is/are the substrate(s)?1 Acetyl CoA 7 Malonyl CoA NADPHATPPalmitrateNAD+FADATPAcetyl CoANADPHATPCholesterolPregnenolone (mother hormone)

What is/are the end product(s)?Palmitate ONLY8 Acetyl CoA7 FADH27 NADHLanosterol Cholesterol

Which step is rate limiting?Acetyl CoA + ATP Malonyl CoAFatty acyl CoA + Carnitine Fatty Acyl carnitine + CoAHMG CoA MevalonateCholesterol Pregnenolone

Rate limiting enzymeAcetyl CoA carboxylaseCarnitine acyltransferaseHMG CoA reductaseDesmolase

Blocker: Aminogluthetimide

DiseasesFatty liverCarnitine deficiencyMCAD deficiencyJamaican vomiting sicknessRefsums diseaseZellwegers syndromeX-linked ALD