Biochemistry 2 - Study Notes PDF

Biochemistry (2) Flow intermediates through metabolic pathways 1) Availability of substrates. 2) Allosteric activation inhibition of rate limiting step enzymes (committed). 3) Reversible phosphorylation (covalent Modification). 4) Induction –repression of enzyme synthesis. Absorptive:-...

Biochemistry (2) Flow intermediates through metabolic pathways 1) Availability of substrates. 2) Allosteric activation inhibition of rate limiting step enzymes (committed). 3) Reversible phosphorylation (covalent Modification). 4) Induction –repression of enzyme synthesis. Absorptive:- 2-4 hr following meal ingestion ↑ Glucose ↑a.a. ↑TAG [in chylomicrons] Pancreatic Islet →↑ insulin → turn absorptive into anabolic in liver, adipose and muscle tissue. Allosteric activation of liver glycolysis ↑ F 2,6BP→ (+) PFK-1 → (+) Glycolysis (-)F1, 6BP→ (-) gluconeogenesis Reversible phosphorylation: most anabolic enzymes are activated by dephosphorylation except Glycogen phosphorylase, HSL and F2,6 BPase are inhibited by dephosphorylation Post absorptive: - as in fasting, burns and Weight reduction ↓insulin / glucagon + ↓substrate availability Thus making fasting catabolic period of TAG, protein, glycogen. Exchange of substrates between liver, muscles, brain and adipose tissues is guarded by 1) Need to maintain adequate glucose for brain energy need. 2) Need to mobilize fatty acid and release ketone bodies from liver. - Changes in fasting are reciprocal of those in well fed →4 mechanisms controlling flow of substrates will achieve opposite effects o enzymes are activated by phosphorylation o substrates, not provided through diet, but catabolism o Brain has neither TAG nor glycogen but Exclusive reliance on glucose. LIVER: Absorptive:- It is a nutrient distribution centre because of portal drainage and it smoothes fluctuations in availability of substrates. CHO: ‫ اﻟﻛﺑد ﯾُدﯾر اﻷﺣﻣﺎض اﻷﻣﯾﻧﯾﺔ ﺑﺗوﺟﯾﮭﮭﺎ ﻧﺣو ﺗﺻﻧﯾﻊ اﻟﺑروﺗﯾﻧﺎت واﻟﻣرﻛﺑﺎت‬،‫ﻓﻲ ﺣﺎﻟﺔ اﻟﺷﺑﻊ‬ ↑glucose phosphorylation G→G6 P ‫ ﯾُرﻛز اﻟﻛﺑد ﻋﻠﻰ‬.‫ أو اﺳﺗﻘﻼﺑﮭﺎ ﻹﻧﺗﺎج اﻟطﺎﻗﺔ وﺗﺧزﯾﻧﮭﺎ ﻛدھون أو ﺟﻠﯾﻛوﺟﯾن‬،‫اﻟﻧﯾﺗروﺟﯾﻧﯾﺔ‬.‫ﺗﻠﺑﯾﺔ اﺣﺗﯾﺎﺟﺎت اﻟﺟﺳم وﺗﺧزﯾن اﻟﻔﺎﺋض ﻟﺿﻣﺎن اﺳﺗﻘرار اﻟﺗوازن اﻷﯾﺿﻲ‬ ↑glycogen synthesis ↑HMP ↑glycolysis (↑insulin/ glucagon) (+) PFK-1→Acetyl CoA→ TCA and Fatty acid ↓gluconeogenesis where ↓acetyl CoA +↑insulin/ glucagan → (-)pyruvate carboxylase and (-) F1,6 BPase Post absorptive:- CHO ↑glycogen degradation and ↑glucagon/insulin → rapid degradation so that 100 g glycogen will be exhausted 10-18 hr into fasting ↑gluconeogenesis 4-6 hr after last meal Fully active as glycogen stores are fully depleted Maintains blood glucose during overnight and prolonged fasting , using c-skeleton of glucogenic a.a., lactate and glycerol Absorptive: FAT ↑ Fatty acid synthesis ↑TAG synthesis →VLDL →muscle, fat 1  ↑glycolysis →glycerol 3P→TAG synthesis PROTEIN - ↑a.a. degradation - for surplus a.a. beyond liver needs to synthesize proteins replacing those degraded during post absorptive Released in to blood for protein synthesis in tissues Surplus a.a. deaminated →C – skeleton →pyruvate, acetylCoA, TCA intermediates → for oxidation and fatty acid synthesis. Post absorptive:- FAT - ↑fatty acid oxidation - ↑ketogenesis : ketone bodies appear in blood and urine on 2nd day of fasting →provide fuel for brain - ↓need for gluconeogenesis from a.a. →↓loss of proteins hydrolysis ADIPOSE TISSUE Absorptive:- CHO ↑ Insulin →↑ glucose flux ↑glycolysis →↑ glycerol 3P ↑HMP Post absorptive:- CHO ↓insulin →↓glucose uptake ↓fatty acid + TAG synthesis Absorptive:- FAT ↑ Fatty acid synthesis ( evident in re-feeding fasting person ) fatty acids mainly supplied by TAG from chylomicrons + VLDL by lipoprotein lipase (activated by insulin ) ↑TAG synthesis ↓ TAG degradation Post absorptive FAT ↑degradation of TAG as HSL-P (+) by epinephrine and norepinephrin ↑release of fatty acids and glycerol →liver gluconeogenesis ↓uptake of fatty acid as lipoprotein lipase activity ↓ →circulating TAG of lipoprotein are not available for TAG synthesis BRAIN Absorptive:- CHO Glucose exclusively primary fuel because there are no glycogen stores, thus completely dependent on blood glucose. FAT No TAG stores Fatty acid does not cross BBB. Post absorptive CHO/ First few days fasting it use glucose exclusively Prolonged fasting (> 2-3 weeks) blood ketone bodies ↑ and used in addition to glucose, as K.B. can cross BBB. MUSCLES 2 Muscles are highly oxidative tissue 30% of O2 αt resting 90% O2 vigorous exercise Resting muscles Absorptive:- CHO ↑insulin → ↑glucose transport ↑glycolysis →↑G6P ↑glycogen synthesis (esp. After depletion following exercise) Post absorptive:- CHO - Fatty acids and ketone bodies are major fuels during resting ↓insulin → ↓glucose transport →↓glucose metabolism ↑glycogen degradation → ↑G6P [but not free glucose] and ↑lactate - If glycogen runs out → fatty acids become dominant energy source [from excessive lipolysis]. Absorptive:- FAT Fatty acids ( from TAG of VLDL and chylomicrons lipoprotein particles) are secondary fuel as glucose is primary fuel a.a. ↑protein synthesis to replace those degraded previously Post absorptive:- FAT first few weeks; fatty acids + ketone bodies > 3 wks →muscle oxidizes fatty acid exclusively ↓ketone bodies use Proteins 1st few days: rapid protein breaks down →a.a. for liver gluconeogenesis After several wks; brain switches to ketone bodies. o ↓ need for gluconeogenesis o ↓need for muscles proteolysis 3