12 - protein digestion & metabolism and gluconeogenesis & urea system

gluconeogenesis

making new glucose from a non-carb source

done in liver

made with lactate, alanine, glycerol

changes to the 3 irreversible steps

1. uses ATP/GTP to turn pyruvate → oxaloacetate → PEP

2. fructose-1,6-bisphosphate → fructose-6-phosphate

3. glucose-6-phosphate → glucose

energy cost: USES ATP (6 ATP = 1 glucose)

protein digestion

begins in the stomach

HCl denatures the proteins, proteases breaks peptide bonds

endopeptidases

attacks the inside of the chain

pepsin, trypsin, chymotrypsin

exopeptidases

carboxypeptidase, aminopeptidase, prolinases

attacks at the very end

zymogens

inactive form of enzymes that need to be activated by cleavage before they work

ex: pepsinogen is the inactive form of pepsin

HCl causes pepsinogen to cleave into pepsin

without HCl, digestion doesn’t happen

pancreatic proteases release zymogens

trypsinogen, chymotrypsinogen, procarboxypeptidase, proelastase

trypsin: master protease

activates the other enzymes

if trypsin is activated too early, everything will be activated too early and attack everything

why are most digestive proteases zymogens?

a way for the body to protect itself from digesting itself

where is the protein broken down

protein in the GI tract is broken down to amino acids and absorbed in the intestine

amino acid pool

protein cant be stored in our body

all protein is functional protein

collective term for all amino acids in the body

added to the pool via diet and removed by excretion

protein recycling

body is constantly breaking down old proteins and making new ones

when they’re broken down the amino acids are reused to make new proteins

nitrogen excretion

amino acids contain nitrogen

when broken down they become ammonia (very toxic)

removed by urea cycle

essential amino acids

can never be substituted for another one, the ribosome just stops if it doesn’t have the right amino acid

if one is lacking in diet, functional protein is broken down to provide them

albumin

most abundant and important protein in the blood

fluid balance regulator

albumin role in osmotic balance

pulls water into blood vessels

prevents edema and maintains blood volume

keeps fluid inside bloodstream

albumin role as a general transporter in the blood

carries a lot of non-water soluble substances

• drugs, fatty acids, hormones

low albumin levels occurs in…

occurs in elderly clients due to malnutrition

clients with liver disease

severe inflammation (increased permeability makes it easier for large molecules like albumin to leak out)

amino acid transportation

Amino acids are absorbed in the small intestine via Na⁺- and H⁺-dependent transport, released into portal blood to the liver, and then distributed through the circulation to tissues for protein synthesis and metabolism.

glycogenolysis

liver stores glycogen are broken down into glucose

• however this is limited and exhausted first

amino acid catabolism + 2 main parts

breaking down amino acids for energy or other uses

• deamination: removing nitrogen

• transamination: using the carbon skeleton

deamination

removing nitrogen from a molecule

produces ammonia

transamination

transfers nitrogen

no ammonia produced

cahill cycle (glucose-alanine cycle)

moves nitrogen from muscle to liver

maintain blood glucose during fasting

transports nitrogen from muscle to liver via alanine while allowing the liver to convert carbon skeletons into glucose for energy supply during fasting

excess nitrogen intake

enters kreb cycle directly

converted to glucose, glycogen or TG

detoxified by the urea cycle

urea synthesis & excretion

• the liver produces urea to excrete nitrogen waste

1. amino acids are deaminated, their carbon skeletons are metabolized to create ATP

2. the free amino group forms toxic ammonia which is converted into urea

3. urea travels in the blood and is filtered out by the kidneys

urea cycle

how the liver converts toxic ammonia into safe urea to be excreted in urine

happens in the liver

uses 3 ATP and produces 2 NADH and detoxifies 2 NH3

1. mitochondrial NH4+ used to make carbamoyl phosphae

2. citrulline formation

3. argininosuccinate formation

4. arginine formation

5. urea formation

OTC deficiency

genetic defect in the urea cycle (missing OTC enzyme)

causes ammonia to build up = hyperammonemia

• ataxia

• lethargy