Biochemistry exam 2 Acetyl Coa and Obesity

Fatty acid synthesis

Cytoplasm

• Intermediates covalent link to SH of acetyl carrier protein

• joined by fatty acid synthase

• MALONYL ACP DONOR

• NADPH reductant

• D-3-hydroxybutryryl ACP intermediate 

Fatty acid oxidation

Mitochondrial matrix

• intermediates attached to SH of CoA

• Acetyl CoA DONOR

• Oxidants NAD and FAD

• L-3-hydroxyacyl CoA intermediate

Even chain synthesis 1-3

1- Acetyl CoA carboxylase- ligase

• Acetyl CoA+ bicarbonate makes malonyl

• ATP hydrolysis 

2- Acetyl transacetylase- transferase

• transfers acetyl group from acetyl CoA to ACP 

3-Malonyl transacetylase- transferase

• link malonyl Coa from 1 to ACP 

Even chain synthesis 4-5

4-B-ketoacyl synthase- transferase

• Condense acetyl ACP from 2 and 3 make acetoacetyl ACP

• release ACP and CO2

5- b-keto reductase- REDOX

• reduce acetoacetyl ACP to D-3-hydroxy ACP

• Use NADPH reducing

Even chain synthesis 6-7

6: 3-hydroxyacyl dehydatase- lyase

• d-3-hydroxb acp dehydrated makes cotonyl ACP 

7- Enyol reductase

• Cotonyl ACP reduced to butryl ACP (4+2 carbons)

Odd chain synthesis differences

Step 2: transfer propinol CoA to ACP

Step 4: propionyl acp condenses

Step 7: a reduced to valeryl ACP 

Synthesis palmitate 

8 acetyl Coa needed

• needs 7 atp, 14 NADPH

oxidation palmitate

produce 8 acetyl coa

• produce 7 nadh, 7 fadh2, 108 atp

Substrate fatty acid: acetyl Coa

• Glycolysis: pyruvate in citoplasm to mitochondria

• then acetyl coa by pyruvate DH

• then from matrix to cytoplasm by citrate shuttle

  • Oxaloacetate +acetyl makes citrate from citrate synthase

Substrate fatty acid: NADPH 

• by ox phase PPP

• produced by malic enzyme (citrate shuttle) 

Unsaturation fatty acids palmitate:

Fatty acid longer 16 carbons

• malonyl Coa carbon donor

Unsaturated fatty acids

• ER membrane (NADH-cyt B, cyt b)

• double bonds yes

Essential fatty acids

• Linoleate and linolenate (not apparently?)

• mammals no double bonds have

Fatty acid synthesis and degradation

by acetyl coa carboxylase

Hormonal regulation

ACC inhibited when phospho by AMP dependent kinase (AMPDK)

• Glucagon and epinephrine activate AMPK, inactivate ACC (degration)

• insulin activate protein phosphatase 2a, inactivate ACC (synthesis)

Local control 

Palmitoyl Coa: inhibit ACC

Citrate: activates ACC

• ACC inhibit fatty acid degradation because malonyl COA prevent fatty acyl coa (inhibit carnitine acyl transferase 1) 

why obesity

• store excess fat

• food drug

• gut microbiome change

• genetic

• process food

Hormones and signaling for caloric homeostasis

Caloric: maintain energy

Cholecystokinin: secrete pancreatic enzyme and bile gallbladder

GLP-1: enhance glucose induced insulin and inhibits glucagon

Leptin: brain

adiponectin: increase insulin sensitivity 

AMP-dependent protein kinase

Activate when energy cell charge low

• Activate catabolic (glycolysis PFK2, glucose GLUT 4, fatty acid OX)

• Inhibit anabolic (FAS, glycogen synthesis, GNG)

Insulin metabolic

• glucose in liver, skeletel, asipose

• activate glycolysis, glycogen synthesis, fatty acid synthesis

Glucagon metabolic

• secrete by pancreas when blood glucose low

• activate GNG, glycogen degradation, and fatty acid export

• no effect brain/skeletel

Epinephrine metabolic

• by adrenal medulla when blood glucose low

• neurotransmitter

Insulin dependent type 1 diabetes

• deficiency pancreatic B cells

  • INSULIN DEPENDENT 

insulin dependent type 2 diabetes

• insulin RESISTANCE

• metformin help 

Starvation

Maintain glucose homeostasis

• glucose to fats

• LIVER CONVERT FATTY ACIDS TO KETONE

Ethanol metabolism

leads to NADH and ACETYL COA excess

NADH high ethanol metabolism

Inhibit GNG, fatty acid OX, CAC

promote lactic

• leads to hypoglycemia and lactic acidosis 

high acetyl coa ethanol metabolism

Promote fatty acid synthesis, ketone body

• fatty liver 

Chronic alcohol

Prevent glutathione regenerated cuz NADPH needed

• acetaldehyde impair protein

• thiamine loss: PDH and A-keto DH failure (wenicke-karsakoff syndrome)